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Lu G, Tu J, Tu J, Jiang R. Case report: Chemotherapy plus sintilimab for the treatment of gastroesophageal junction hepatoid adenocarcinoma with liver metastasis: a case study with literature review. Front Immunol 2025; 16:1513604. [PMID: 39931054 PMCID: PMC11808132 DOI: 10.3389/fimmu.2025.1513604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 01/08/2025] [Indexed: 02/13/2025] Open
Abstract
Objective To elucidate the clinicopathological features and treatment of metastatic gastroesophageal junction hepatoid adenocarcinoma (GEJ HAC)using a case study and literature review. Methods Clinical presentation, results of histology and immunohistochemistry, and next-generation sequencing(NGS) in a patient with GEJ HAC metastasizing to the liver were reviewed. Chemotherapy (SOX or S-1) plus sintilimab was administered. Results A 65-year-old male patient with a history of hypertension was admitted to the hospital due to a one-week increase in serum AFP levels. There was a small intraluminal mass at the GEJ and a metastatic lesion in liver segment VIII, as well as enlarged perigastric and retroperitoneal lymph nodes. Tumor cells in both the GEJ and liver tissue exhibited a glandular shape with a nest-like adenoid structure. Immunohistochemical (IHC) analysis of the GEJ tissue showed positivity for AFP, CA19-9, CK7, CK20, MUC-1, P53 (wild type), Glypican-3, and HepPar-1, and negativity for Arginase-1, CD10, and Her-2. In the metastatic liver tissue, IHC testing demonstrated positivity for AFP, CD10, CK19, CK20, HepPar-1, MUC-1, Ki-67, and P53 (wild type), while CK7 was negative. The NGS report of GEJ mass indicated that the JAK2 and TP53 genes harbored missense mutations, while the MLH1, MSH2, MSH6, PMS2, ERBB2, EGFR, PIK3CA, APC, CTNNB1, CDH1, and DPYD genes were normal. The patient's serum levels of CEA, CA19-9, and AFP were sharply decreased. The patient achieved a major pathological response (MPR) and remains in a progression-free stage. Conclusions Sintilimab-based chemotherapy has proven efficacy in achieving a MPR and maintaining a progression-free state for a patient with GEJ HAC that has metastasized to the liver.
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Affiliation(s)
- Genlin Lu
- Department of General Surgery (Key Disciplines of Medicine in Quzhou City), Longyou County People’s, Longyou People’s Hospital Affiliated with Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Quzhou, China
| | - Jiarui Tu
- Clinical Medicine Department, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jinming Tu
- Department of Gastroenterology, Longyou County People’s Hospital, Longyou People’s Hospital Affiliated with Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Quzhou, China
| | - Renya Jiang
- Department of Hepatobiliary Surgery, Quzhou City People’s Hospital, Quzhou, China
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Li L, Zhang D, Zhu J, Zhang G. Hepatoid adenocarcinoma of the stomach with ideal response to neoadjuvant chemo-immunotherapy: a case report. Front Immunol 2025; 15:1496342. [PMID: 39845967 PMCID: PMC11750875 DOI: 10.3389/fimmu.2024.1496342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 12/18/2024] [Indexed: 01/24/2025] Open
Abstract
Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer characterized by histological features resembling hepatocellular carcinoma. Surgical intervention remains the preferred treatment modality for eligible patients. However, the efficacy of neoadjuvant therapy and alternative treatment regimens has been found to be suboptimal. Consequently, due to the high metastatic potential and unfavorable biological behavior of HAS, the prognosis for affected patients is exceedingly poor. We present a case involving a 64-year-old male diagnosed with advanced HAS, who demonstrated significant antitumor responses following a preoperative regimen of chemotherapy combined with immunotherapy, specifically utilizing oxaliplatin, S-1, and sintilimab. Over a 2-month period of neoadjuvant therapy, the patient's serum α-fetoprotein level significantly decreased from 52,951.56 ng/mL to 241.04 ng/mL. Computed tomography scans revealed substantial tumor regression. Subsequent radical surgical intervention confirmed significant tumor shrinkage, with no evidence of lymph node metastasis upon pathological examination. This is the first report of chemotherapy combined with sintilimab in the treatment of gastric hepatoid adenocarcinoma, which may provide novel insights into the therapeutic strategy for HAS.
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Affiliation(s)
- Linchuan Li
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Laboratory of Metabolism and Gastrointestinal Tumor, Shandong, China
| | - Dexu Zhang
- Shandong Provincial Qianfoshan Hospital, Shandong University, Shandong, China
| | - Jiankang Zhu
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Laboratory of Metabolism and Gastrointestinal Tumor, Shandong, China
| | - Guangyong Zhang
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Laboratory of Metabolism and Gastrointestinal Tumor, Shandong, China
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Huang YQ, Huang ZN, Hong QQ, Zhang P, Zhang ZZ, He L, Shang L, Wang LJ, Sun YF, Li ZX, Liu JJ, Ding FH, Lin ED, Fu YA, Lin SM, Chen QY, Zheng CH, Huang CM, Li P. Development of a staging system for hepatoid adenocarcinoma of the stomach based on multicenter data: a retrospective cohort study. Int J Surg 2025; 111:718-727. [PMID: 39316640 PMCID: PMC11745678 DOI: 10.1097/js9.0000000000001768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 05/27/2024] [Indexed: 09/26/2024]
Abstract
BACKGROUND Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC) with a poor prognosis. Furthermore, the current pathological staging system for HAS does not distinguish it from that for common gastric cancer (CGC). METHODS The clinicopathological data of 251 patients with primary HAS who underwent radical surgery at 14 centers in China from April 2004 to December 2019 and 5082 patients with primary CGC who underwent radical surgery at two centers during the same period were retrospectively analyzed. A modified staging system was established based on the differences in survival. RESULTS After 1:4 propensity score matching (PSM), 228 patients with HAS and 828 patients with CGC were analyzed. Kaplan-Meier (K-M) analysis showed patients with HAS had a poorer prognosis compared with CGC. Multivariate analysis identified pN stage, CEA level, and perineural invasion (PNI) as independent prognostic factors in patients with HAS. A modified pT (mpT) staging was derived using recursive partitioning analysis (RPA) incorporating PNI and pT staging. The modified pathological staging system (mpTNM) integrated the mpT and the eighth American Joint Committee on Cancer (AJCC) pN definitions. Multivariate analysis showed that the mpTNM stage outperformed other pathological variables as independent predictors of OS and RFS in patients with HAS. The mpTNM staging system exhibited significantly higher predictive accuracy for 3-year OS in patients with HAS (0.707, 95% CI: 0.650-0.763) compared to that of the eighth AJCC staging system (0.667, 95% CI: 0.610-0.723, P <0.05). Analysis using the Akaike information criterion favored the mpTNM staging system over the eighth AJCC staging system (824.69 vs. 835.94) regarding the goodness of fit. The mpTNM stages showed improved homogeneity in survival prediction (likelihood ratio: 41.51 vs. 27.10). Comparatively, the mpTNM staging system outperformed the eighth AJCC staging system in survival prediction, supported by improvements in the net reclassification index (NRI: 47.7%) and integrated discrimination improvement (IDI: 0.083, P <0.05). The time-dependent ROC curve showed that the mpTNM staging system consistently outperformed the eighth AJCC staging system with increasing observation time. CONCLUSION The mpTNM staging system exhibited superior postoperative prognostic accuracy for patients with HAS compared to the eighth AJCC staging system.
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Affiliation(s)
- Ying-Qi Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Ze-Ning Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Qing-Qi Hong
- Department of Gastrointestinal Oncology Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China
| | - Peng Zhang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Zi-Zhen Zhang
- Department of Gastrointestinal Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
| | - Liang He
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, People’s Republic of China
| | - Liang Shang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China
| | - Lin-Jun Wang
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China
| | - Ya-Feng Sun
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, People’s Republic of China
| | - Zhi-Xiong Li
- Gastrointestinal Surgery Unit 1, Teaching Hospital of Putian First Hospital of Fujian Medical University, Putian, People’s Republic of China
| | - Jun-Jie Liu
- Gastrointestinal Department of The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Fang-Hui Ding
- General Surgery Department, The First Hospital of Lanzhou University, Lanzhou, People’s Republic of China
| | - En-De Lin
- Department of General Surgery, Zhongshan Hospital Affiliated with Xiamen University, Xiamen, People’s Republic of China
| | - Yong-An Fu
- Department of Gastrointestinal Surgery, Affiliated Quanzhou First Hospital to Fujian Medical University, Quanzhou, People’s Republic of China
| | - Shuang-Ming Lin
- Department of Gastrointestinal Surgery, Longyan First Hospital Affiliated with Fujian Medical University, Longyan, People’s Republic of China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People’s Republic of China
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Loscocco GG, Vannucchi M, Santi R, Amorosi A, Scarpino S, Siciliano MC, Guglielmelli P, Tripodo C, Di Napoli A, Vannucchi AM. Hepatoid thymic carcinoma in a polycythemia vera patient treated with ropeginterferon Alfa-2b: Clinical, histopathological and molecular correlates. Pathol Res Pract 2024; 263:155648. [PMID: 39405803 DOI: 10.1016/j.prp.2024.155648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 09/14/2024] [Accepted: 10/07/2024] [Indexed: 11/10/2024]
Abstract
Hepatoid thymic carcinoma (HTC) is an extremely rare variant of primary epithelial tumor of the thymus morphologically resembling hepatocellular carcinoma Herein, we report an additional case of HTC diagnosed in a 40-years-old man affected by polycythemia vera and treated with ropeginterferon alfa 2-b, for the first time deeply analyzing the molecular profile of this distinctive thymic malignancy. By immunohistochemistry, tumor cells were positive for cytokeratin 7-19, GLUT1, and Hep-Par-1, whereas AFP tested negative. Whole exome sequencing revealed loss of function mutations in TP53, STK11, PBRM1, SMAD3, FN1, NTRK1, and FANCD2, as well as gain of function mutations in MTOR, BCL11A and COL1A1, along with amplification of CCND3 and MDM2. This mutational landscape halfway between thymic carcinoma (TP53, PBRM1) and hepatoid variant carcinoma of other sites (STK11) suggests that, at some point during carcinogenesis, a switch occurred from an epithelial thymic phenotype to a hepatoid-like one.
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Affiliation(s)
- Giuseppe G Loscocco
- Department of Experimental and Clinical Medicine, CRIMM, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy
| | | | - Raffaella Santi
- Pathology Section, Department of Health Sciences, University of Florence, Florence, Italy
| | - Andrea Amorosi
- Department of Health Sciences, "Magna Graecia" University of Catanzaro, Catanzaro, Italy
| | - Stefania Scarpino
- Department of Clinical and Molecular Medicine, Sapienza University, Sant'Andrea Hospital, Rome, Italy
| | | | - Paola Guglielmelli
- Department of Experimental and Clinical Medicine, CRIMM, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy
| | - Claudio Tripodo
- Tumor Immunology Unit, Department of Health Sciences, University of Palermo, Palermo, Italy; IFOM-ETS-The AIRC Institute of Molecular Oncology, Milan, Italy
| | - Arianna Di Napoli
- Department of Clinical and Molecular Medicine, Sapienza University, Sant'Andrea Hospital, Rome, Italy
| | - Alessandro M Vannucchi
- Department of Experimental and Clinical Medicine, CRIMM, Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy.
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Gu X, Rong J, Zhu L, Dai Z, Ren S, Chen J, Yin B, Wang Z. Hepatoid adenocarcinoma of the stomach: discrimination from conventional gastric adenocarcinoma with a computed tomography-based radiomics nomogram. J Gastrointest Oncol 2024; 15:2041-2052. [PMID: 39554578 PMCID: PMC11565099 DOI: 10.21037/jgo-24-210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Accepted: 09/04/2024] [Indexed: 11/19/2024] Open
Abstract
Background Previous studies found it difficult to differentiate hepatoid adenocarcinoma of the stomach (HAS) from conventional gastric adenocarcinoma (CGA). We aimed to assess the efficacy of a computed tomography (CT)-based radiomics nomogram in identifying HAS. Methods Portal phase CT images were collected from 59 patients with HAS and 122 patients with CGA. HAS and CGA were differentiated through univariate analysis of clinical characteristics, serum biochemical biomarkers, and CT features. The construction of the radiomics signature involved the application of the least absolute shrinkage and selection operator (LASSO) regression model. Multivariable logistic regression analysis was employed to establish the CT-based radiomics nomogram. Results The separation of HAS patients from CGA patients relied on the serum alpha-fetoprotein (AFP) level and radiomics signature. The area under the curve (AUC) of AFP was 0.726 [95% confidence interval (CI): 0.639-0.801] in the training cohort and 0.681 (95% CI: 0.541-0.800) in the test cohort, whereas the radiomic signature demonstrated a significantly higher AUC of 0.949 (95% CI: 0.895-0.980) in the training cohort and 0.868 (95% CI: 0.749-0.944) in the test cohort. The nomogram model yielded excellent accuracy for identifying HAS, achieving an AUC of 0.970 (95% CI: 0.923-0.992) in the training cohort and 0.905 (95% CI: 0.796-0.968) in the test cohort. Conclusions Radiomics analysis offers promise for differentiating HAS from CGA, and the CT-based radiomics nomogram is likely to have significant clinical implications on HAS distinction.
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Affiliation(s)
- Xiaoyu Gu
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China
| | - Jian Rong
- The Key Laboratory of Broadband Wireless Communication and Sensor Network Technology (Ministry of Education), Nanjing University of Posts and Telecommunications, Nanjing, China
| | - Li Zhu
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhaoyan Dai
- The Key Laboratory of Broadband Wireless Communication and Sensor Network Technology (Ministry of Education), Nanjing University of Posts and Telecommunications, Nanjing, China
| | - Shuai Ren
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jianxin Chen
- The Key Laboratory of Broadband Wireless Communication and Sensor Network Technology (Ministry of Education), Nanjing University of Posts and Telecommunications, Nanjing, China
| | - Bo Yin
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China
| | - Zhongqiu Wang
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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Bathobakae L, Elagami M, Mahmoud A, Kesrani J, Yuridullah R, Melki G, Akmal A, Cavanagh Y, Baddoura W. Alpha-Fetoprotein-Producing Hepatoid Adenocarcinoma of the Stomach. J Med Cases 2024; 15:304-309. [PMID: 39328799 PMCID: PMC11424106 DOI: 10.14740/jmc4263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Accepted: 08/27/2024] [Indexed: 09/28/2024] Open
Abstract
Hepatoid adenocarcinoma of the stomach (HAS) is a rare type of gastric cancer with unique clinicopathological features. HAS has a poor prognosis because of early liver, lung, and lymph node metastasis. Owing to its rarity and malignant potential, data on its pathophysiology and management are scarce. Herein, we describe a case of alpha-fetoprotein-producing HAS (AFP-HAS) with metastases to the liver, lungs, and spine. The patient presented with a 3-month history of epigastric pain and intractable emesis, initially thought to be gastroparesis given her uncontrolled diabetes mellitus. Contrast-enhanced computerized tomography (CECT) of the abdomen and pelvis revealed thickening of the gastric wall with hepatic metastases. Upper endoscopy revealed a fungating gastric mass, and the histopathology confirmed AFP-HAS. The patient did not tolerate palliative chemotherapy and died 6 months after her gastric cancer diagnosis.
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Affiliation(s)
- Lefika Bathobakae
- Internal Medicine, St. Joseph’s University Medical Center, Paterson, NJ, USA
| | - Mohamed Elagami
- Gastroenterology and Hepatology, St. Joseph’s University Medical Center, Paterson, NJ, USA
| | - Anas Mahmoud
- Internal Medicine, St. Joseph’s University Medical Center, Paterson, NJ, USA
| | - Jaydev Kesrani
- Hematology and Oncology, St. Joseph’s University Medical Center, Paterson, NJ, USA
| | - Ruhin Yuridullah
- Gastroenterology and Hepatology, St. Joseph’s University Medical Center, Paterson, NJ, USA
| | - Gabriel Melki
- Gastroenterology and Hepatology, St. Joseph’s University Medical Center, Paterson, NJ, USA
| | - Amer Akmal
- Pathology and Laboratory Medicine, St. Joseph’s University Medical Center, Paterson, NJ, USA
| | - Yana Cavanagh
- Gastroenterology and Hepatology, St. Joseph’s University Medical Center, Paterson, NJ, USA
| | - Walid Baddoura
- Gastroenterology and Hepatology, St. Joseph’s University Medical Center, Paterson, NJ, USA
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Deng H, Wang L, Li Z, Zhan T, Huang L. Optimal treatment strategies for hepatoid adenocarcinoma of the lung: insights from a comprehensive analysis. BMC Cancer 2024; 24:948. [PMID: 39095810 PMCID: PMC11297620 DOI: 10.1186/s12885-024-12682-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 07/24/2024] [Indexed: 08/04/2024] Open
Abstract
BACKGROUND Hepatoid adenocarcinoma of the lung (HAL) is a distinctly uncommon subtype of lung adenocarcinoma (LAC), characterized by hepatoid features and an alarmingly low 5-year survival rate of approximately 8%. The scarcity of information on this condition has contributed to the absence of standardized treatment protocols, and the molecular underpinnings of its pathogenesis remain largely unexplored. To bridge these gaps, this study compiled data from 191 primary HAL patients to delineate treatment patterns, prognostic factors, and potential pathogenic mechanisms. METHODS This study was divided into two cohorts: cohort 1, comprising 110 patients extracted from the Surveillance, Epidemiology, and End Results (SEER) database, and cohort 2, consisting of 70 patients identified through a comprehensive literature review via the PubMed, Web of Science, and Scopus databases, in addition to 11 patients from Tongji Hospital. The Cox proportional hazards regression model was employed to identify independent prognostic factors. Kaplan-Meier survival curves were generated to assess the impact of treatment modalities centered around surgery and chemotherapy. Moreover, this study evaluated the efficacy of first-line treatment regimens and conducted Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses on identified mutated genes. RESULTS The demographic and clinical profile of HAL patients typically comprises older individuals who are smokers, with a predisposition for diagnosis at advanced disease stages, culminating in a high mortality rate. Key prognostic indicators identified included disease stage, chemotherapy and surgical interventions. The study suggests a treatment strategy that advocates chemotherapy for patients with stage IV HAL and surgery for those with non-stage IV disease. The combination of paclitaxel and platinum-based chemotherapy emerged as an efficacious first-line treatment, with the integration of immunotherapy and targeted therapies showing potential benefits. Genetic analysis underscored similarities between HAL and LAC, particularly highlighting aberrant kinase activity (serine, threonine, and tyrosine) and the activation of PI3K-Akt and MAPK signaling pathways as contributing factors to HAL pathogenesis. CONCLUSION Despite its relatively rare occurrence, this study underscores the significance of treatment strategies and concludes probable prognostic factors. Due to limited reports, a deeper understanding of the molecular mechanisms driving tumorigenesis and progression in HAL is needed.
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Affiliation(s)
- Huijing Deng
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Aviation Road, Wuhan, Hubei Province, 430030, China
- The Second Clinical Medical College, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430000, China
| | - Luyao Wang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Aviation Road, Wuhan, Hubei Province, 430030, China
| | - Zewei Li
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Aviation Road, Wuhan, Hubei Province, 430030, China
- The Second Clinical Medical College, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430000, China
| | - Tao Zhan
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Aviation Road, Wuhan, Hubei Province, 430030, China
- The Second Clinical Medical College, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430000, China
| | - Liu Huang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Aviation Road, Wuhan, Hubei Province, 430030, China.
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Zhu Y, Ying L. Hepatoid adenocarcinoma of the stomach. WORLD CHINESE JOURNAL OF DIGESTOLOGY 2024; 32:412-417. [DOI: 10.11569/wcjd.v32.i6.412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/29/2024]
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Wei J, Ji K, Zhang Y, Zhang J, Wu X, Ji X, Zhou K, Yang X, Lu H, Wang A, Bu Z. Exploration of molecular markers related to chemotherapy efficacy of hepatoid adenocarcinoma of the stomach. Cell Oncol (Dordr) 2024; 47:677-693. [PMID: 37943484 DOI: 10.1007/s13402-023-00892-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/08/2023] [Indexed: 11/10/2023] Open
Abstract
PURPOSE Preoperative neoadjuvant chemotherapy may not improve the prognosis of patients with hepatoid adenocarcinoma of the stomach (HAS), a rare pathological type of gastric cancer. Thus, the study aimed at the genomic and transcriptomic impacts of preoperative chemotherapy on HAS. METHODS Patients with HAS who underwent surgical resection at Peking University Cancer Hospital were retrospectively included in this study. Whole exome sequencing and transcriptome sequencing were performed on pre-chemotherapy, non-chemotherapy and post-chemotherapy samples. We then compared the alterations in molecular markers between the post-chemotherapy and non-chemotherapy groups, and between the chemotherapy-effective and chemotherapy-ineffective groups, respectively. RESULTS A total of 79 tumor samples from 72 patients were collected. Compared to the non-chemotherapy group, the mutation frequencies of several genes were changed after chemotherapy, including TP53. In addition, there was a significant increase in the frequency of frameshift mutations and cytosine transversion to adenine (C > A), appearance of COSMIC signature 6 and 14, and a reduced gene copy number amplification. Interestingly, the same phenomenon was observed in chemotherapy-ineffective patients. In addition, many HAS patients had ERBB2, FGFR2, MET and HGF gene amplification. Moreover, the expression of immune-related genes, especially those related to lymphocyte activation, was down-regulated after chemotherapy. CONCLUSION Chemotherapy is closely associated with changes in the molecular characteristics of HAS. After chemotherapy, at genomic and transcriptome level, many features were altered. These changes may be molecular markers of poor chemotherapeutic efficacy and play an important role in chemoresistance in HAS. In addition, ERBB2, FGFR2, MET and HGF gene amplification may be potential therapeutic targets for HAS.
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Affiliation(s)
- Jingtao Wei
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Ke Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Yue Zhang
- Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China
- The Cardiomyopathy Research Group at Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Beijing, 100037, China
| | - Ji Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Xiaojiang Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Xin Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Kai Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Xuesong Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Hongfeng Lu
- Berry Genomics Corporation, Beijing, 102206, China
| | - Anqiang Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China.
| | - Zhaode Bu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China.
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10
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Yang X, Wu Y, Wang A, Ma X, Zhou K, Ji K, Ji X, Zhang J, Wu X, Li Z, Bu Z. Immunohistochemical characteristics and potential therapeutic regimens of hepatoid adenocarcinoma of the stomach: a study of 139 cases. J Pathol Clin Res 2024; 10:e343. [PMID: 37974386 PMCID: PMC10766033 DOI: 10.1002/cjp2.343] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 08/13/2023] [Accepted: 08/28/2023] [Indexed: 11/19/2023]
Abstract
Hepatoid adenocarcinoma of stomach (HAS) is a special subtype of gastric cancer with poor prognosis. Immunohistochemical analysis could provide important clues for the treatment of HAS. A total of 159 patients were diagnosed as HAS and 139 were enrolled in this study. Statistical differences were determined using relative test methods and survival analyses were performed by the Kaplan-Meier method to find survival differences. All tumors in this study were negative for Epstein-Barr virus-encoded small RNAs (EBERs) and almost all showed no loss of mismatch repair (MMR) proteins and were positive for alpha fetoprotein (AFP or spalt like transcription factor 4 (SALL4). About half of the tumors had a positive programmed death-ligand 1 combined positive score (CPS) and 17.3% were positive for human epidermal growth factor receptor 2 (HER2). In addition, there was a relatively high proportion of cmet expression. We also found that HAS patients with recurrent disease treated by emerging therapy had a better survival than those treated with traditional chemotherapy (p = 0.002, median recurrence-to-death survival: 23 months versus 6 months); HAS patients who received anti-HER2 therapy or harbored MMR deficiency had favorable prognosis. Overall, high proportions of MMR protein proficiency, positivity for AFP or SALL4, overexpression of HER2, CPS and cmet, as well as negative EBER findings, are distinctive characteristics of HAS patients. While negative EBER and MMR proficiency indicate molecular features of HAS, positivity for AFP or SALL4 could aid in the diagnosis of HAS. In addition, HAS patients could benefit from anti-HER2 therapy, immunotherapy, and anti-angiogenesis therapy.
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Affiliation(s)
- Xuesong Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Yan Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of PathologyPeking University Cancer Hospital & InstituteBeijingPR China
| | - Anqiang Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Xiuli Ma
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of PathologyPeking University Cancer Hospital & InstituteBeijingPR China
| | - Kai Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Ke Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Xin Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Ji Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - Xiaojiang Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
| | - ZhongWu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of PathologyPeking University Cancer Hospital & InstituteBeijingPR China
| | - Zhaode Bu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal CancerPeking University Cancer Hospital & InstituteBeijingPR China
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11
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Zhang R, Yu Y, Zheng J, Pi S, Li J, Chen J. A case report of two instances of colorectal hepatoid adenocarcinoma, accompanied by a comprehensive literature review. J Cancer Res Clin Oncol 2023; 149:18241-18252. [PMID: 37950062 PMCID: PMC10725335 DOI: 10.1007/s00432-023-05488-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Accepted: 10/20/2023] [Indexed: 11/12/2023]
Abstract
OBJECTIVE The study aimed to explore the clinical and pathological characteristics, survival outcomes, and prognostic factors of colorectal hepatoid adenocarcinoma. METHODS We performed two cases of colorectal hepatoid adenocarcinoma treated at the Oncology Department of the First Affiliated Hospital of Nanchang University. We also reviewed literature up to the present and performed a retrospective study of colorectal hepatoid adenocarcinoma. RESULTS Among the 39 patients included in this study, 28 had primary tumors in the colon, 9 in the rectum, and 2 in the rectosigmoid junction. The median age was 52 years (range 31-75 years); 28 patients (71.8%) were male. Out of the 32 patients for whom survival data were available, 24 patients succumbed to disease-related causes. The median overall survival of 32 patients was 8 months, with 1-year and 2-year overall survival rates of 31.0% and 16.0%, respectively. Univariate analysis revealed that depth of infiltration, presence of liver metastases, TNM stage, and the completeness of surgical resection were significantly associated with the overall survival period of colorectal hepatoid adenocarcinoma. CONCLUSION Colorectal hepatoid adenocarcinoma exhibits a high degree of aggressiveness and poor prognosis. The major strategy for early-stage HAC was radical surgery and chemoradiotherapy demonstrates limited efficacy for extending survival.
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Affiliation(s)
- Ran Zhang
- Department of Oncology, The First Affiliated Hospital, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Yi Yu
- Department of Oncology, The First Affiliated Hospital, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Jinxiu Zheng
- Department of Oncology, The First Affiliated Hospital, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Sijie Pi
- Department of Pathology and Pathophysiology, School of Basic Medical and Biological Sciences, Soochow University, Suzhou, 215000, Jiangsu, China
| | - Junhe Li
- Department of Oncology, The First Affiliated Hospital, Nanchang University, Nanchang, 330006, Jiangxi, China.
| | - Jun Chen
- Department of Oncology, The First Affiliated Hospital, Nanchang University, Nanchang, 330006, Jiangxi, China.
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12
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Huang ZN, Huang YQ, Hong QQ, Zhang P, Zhang ZZ, He L, Shang L, Wang LJ, Sun YF, Li ZX, Liu JJ, Ding FH, Lin ED, Fu YA, Lin SM, Lu J, Zheng CH, Huang CM, Li P. Long-term prognostic benefit of adjuvant chemotherapy for patients with hepatoid adenocarcinoma of the stomach after radical resection: A national multicenter study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:106975. [PMID: 37474342 DOI: 10.1016/j.ejso.2023.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 06/10/2023] [Accepted: 07/02/2023] [Indexed: 07/22/2023]
Abstract
BACKGROUND There is no consensus on whether adjuvant chemotherapy (AC) is effective for hepatoid adenocarcinoma of the stomach (HAS). The aim of this study was to investigate the relationship between AC and the long-term prognosis of patients with HAS. METHODS The clinicopathological data of 239 patients with primary HAS who underwent radical surgery from April 1, 2004 to December 31, 2019 in 14 centers in China were retrospectively analyzed. Patients were divided into the AC group (127 patients) and the nonadjuvant chemotherapy (NAC) group (112 patients). RESULTS Kaplan‒Meier (KM) analysis showed that there were no significant differences in the 1-year3-year overall survival rate (OS) and 1-year, 3-year recurrence-free survival rate (RFS) between the AC group and the NAC group (1-year OS: 85.6% vs. 79.8%, 3-year OS: 59.8% vs. 62.4%, 1-year RFS: 69.8% vs. 74.4%, 3-year RFS: 57.2% vs. 55.9%, all P > 0.05). The subpopulation treatment effect pattern plots (STEPP) did not show treatment heterogeneity of AC in patients with HAS. The proportions of local recurrence and metastasis sites in the two groups were similar. Although the smoothed hazard curves of the NAC and AC groups crossed, the peak hazard time was later in the AC group (5.9 and 4.7 months), and the peak hazard rate was lower (0.032 and 0.038, P = 0.987). CONCLUSION The current AC regimen may not significantly improve the survival of patients with HAS after radical surgery.
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Affiliation(s)
- Ze-Ning Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Ying-Qi Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Qing-Qi Hong
- Department of Gastrointestinal Oncology Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Peng Zhang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zi-Zhen Zhang
- Department of Gastrointestinal Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Liang He
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, China
| | - Liang Shang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Lin-Jun Wang
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ya-Feng Sun
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Zhi-Xiong Li
- Gastrointestinal Surgery Unit 1, Teaching Hospital of Putian First Hospital of Fujian Medical University, Putian, China
| | - Jun-Jie Liu
- Gastrointestinal Department of the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Fang-Hui Ding
- General Surgery Department, The First Hospital of Lanzhou University, Lanzhou, China
| | - En-De Lin
- Department of General Surgery, Zhongshan Hospital Affiliated with Xiamen University, Xiamen, China
| | - Yong-An Fu
- Department of Gastrointestinal Surgery, Affiliated Quanzhou First Hospital to Fujian Medical University, Quanzhou, China
| | - Shuang-Ming Lin
- Department of Gastrointestinal Surgery, Longyan First Hospital Affiliated with Fujian Medical University, Longyan, China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
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13
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Amioka J, Yanagawa S, Yamamoto Y, Nakahara M, Yonehara S, Noriyuki T. Hepatoid adenocarcinoma of the stomach effectively treated with capecitabine with oxaliplatin as adjuvant chemotherapy: A case report and literature review. Int J Surg Case Rep 2023; 112:108963. [PMID: 37856969 PMCID: PMC10667871 DOI: 10.1016/j.ijscr.2023.108963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 10/11/2023] [Accepted: 10/11/2023] [Indexed: 10/21/2023] Open
Abstract
INTRODUCTION Hepatoid adenocarcinoma of the stomach (HAS) is an alpha-fetoprotein (AFP)-producing gastric carcinoma (GC) with a hepatocellular carcinoma-like histology. HAS is a relatively rare type of GC, with liver metastases being more common than peritoneal dissemination in the recurrent form, and the poor prognosis. PRESENTATION OF CASE We present the case of a 70-year-old patient who underwent distal gastrectomy for GC and immunohistologically diagnosed as HAS. The patient had an intravenous tumor thrombus at the proximal margin of the resected stomach. Owing to the low possibility of radical resection and high probability of liver metastatic recurrence, capecitabine with oxaliplatin (CapeOX) was started as adjuvant chemotherapy (AC). After three courses of CapeOX, oxaliplatin was discontinued due to adverse events (peripheral neuropathy, grade3) and capecitabine alone was continued for 3 years postoperatively. Six years after surgery, no local recurrence or distant metastasis was detected on imaging studies. DISCUSSION There is no established standard treatment for HAS. Recently, some studies have reported the efficacy of antimetabolites or platinum-based drugs as AC regimens. We thus decided to start a regimen consisting of a combination of antimetabolites and a platinum, i.e., CapeOX, which proved efficacious. CONCLUSION CapeOX or capecitabine may be effective as AC for treating HAS.
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Affiliation(s)
- Jun Amioka
- Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara, Onomichi, Hiroshima, Japan
| | - Senichiro Yanagawa
- Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara, Onomichi, Hiroshima, Japan.
| | - Yuji Yamamoto
- Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara, Onomichi, Hiroshima, Japan
| | - Masahiro Nakahara
- Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara, Onomichi, Hiroshima, Japan
| | - Shuji Yonehara
- Department of Pathology, Onomichi General Hospital, 1-10-23 Hirahara, Onomichi, Hiroshima, Japan
| | - Toshio Noriyuki
- Department of Surgery, Onomichi General Hospital, 1-10-23 Hirahara, Onomichi, Hiroshima, Japan
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14
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Yan XY, Ju HY, Hou FJ, Li XT, Yang D, Tang L, Wang YK, Li ZW, Sun YS, Gao SY. Analysis of enhanced CT imaging signs and clinicopathological prognostic factors in hepatoid adenocarcinoma of stomach patients with radical surgery: a retrospective study. BMC Med Imaging 2023; 23:167. [PMID: 37884901 PMCID: PMC10604919 DOI: 10.1186/s12880-023-01125-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 10/14/2023] [Indexed: 10/28/2023] Open
Abstract
BACKGROUND To investigate the association between CT signs and clinicopathological features and disease recurrence in patients with hepatoid adenocarcinoma of stomach (HAS). METHODS Forty nine HAS patients undergoing radical surgery were retrospectively collected. Association between CT and clinicopathological features and disease recurrence was analyzed. Multivariate logistic model was constructed and evaluated for predicting recurrence by using receiver operating characteristic (ROC) curve. Survival curves between model-defined risk groups was compared using Kaplan-Meier method. RESULTS 24(49.0%) patients developed disease recurrence. Multivariate logistic analysis results showed elevated serum CEA level, peritumoral fatty space invasion and positive pathological vascular tumor thrombus were independent factors for disease recurrence. Odds ratios were 10.87 (95%CI, 1.14-103.66), 6.83 (95%CI, 1.08-43.08) and 42.67 (95%CI, 3.66-496.85), respectively. The constructed model showed an area under ROC of 0.912 (95%CI,0.825-0.999). The model-defined high-risk group showed poorer overall survival and recurrence-free survival than the low-risk group (both P < 0.001). CONCLUSIONS Preoperative CT appearance of peritumoral fatty space invasion, elevated serum CEA level, and pathological vascular tumor thrombus indicated poor prognosis of HAS patients.
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Affiliation(s)
- Xin-Yue Yan
- Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, No. 52 Fu Cheng Road, Beijing, Hai Dian District, 100142, China
| | - Hai-Yue Ju
- Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, No. 52 Fu Cheng Road, Beijing, Hai Dian District, 100142, China
| | - Fang-Jing Hou
- Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, No. 52 Fu Cheng Road, Beijing, Hai Dian District, 100142, China
| | - Xiao-Ting Li
- Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, No. 52 Fu Cheng Road, Beijing, Hai Dian District, 100142, China
| | - Ding Yang
- Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, No. 52 Fu Cheng Road, Beijing, Hai Dian District, 100142, China
| | - Lei Tang
- Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, No. 52 Fu Cheng Road, Beijing, Hai Dian District, 100142, China
| | - Ya-Kun Wang
- Department of Digestive Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, No. 52 Fu Cheng Road, Beijing, Hai Dian District, 100142, China
| | - Zhong-Wu Li
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, No. 52 Fu Cheng Road, Beijing, Hai Dian District, 100142, China
| | - Ying-Shi Sun
- Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, No. 52 Fu Cheng Road, Beijing, Hai Dian District, 100142, China.
| | - Shun-Yu Gao
- Department of Radiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, No. 52 Fu Cheng Road, Beijing, Hai Dian District, 100142, China.
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15
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Neyrand S, Bringuier PP, Benzerdjeb N, Hervieu V, Fenouil T. [Differential diagnostic between hepatocellular carcinoma and hepatoid carcinoma with bone metastasis revelation: What tools can be used?]. Ann Pathol 2023; 43:407-411. [PMID: 36822899 DOI: 10.1016/j.annpat.2023.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 07/26/2022] [Accepted: 01/04/2023] [Indexed: 02/23/2023]
Abstract
Bone metastases of hepatocellular carcinoma (HCC) are rare and disease-revealing bone metastasis are exceptional. Here, we report the case of a 69-year-old man with a cervical vertebral metastasis of hepatocellular carcinoma. Morphological aspect of a metastatic tumor with eosinophilic and polygonal cells raises the question of the differential diagnosis between a localization of a hepatocellular carcinoma or an hepatoid carcinoma, notably when the metastasis is the first clinical manifestation. The morphological aspect by itself does not provide strong enough arguments for diagnosis. Well selected immunohistochemical markers can sometimes help to orientate towards one of the two hypotheses, in particular SALL4 and LIN28 which are in favour of hepatoid carcinoma when both are positive. Finally, as these two entities have different molecular profiles, molecular study can also be helpful to distinguish them. Indeed, HCCs often present TERT promoter, CTNNB1 mutations and IL-6/JAK/STAT pathway activation while hepatoid adenocarcinoma frequently presents chromosome 20 long arm gain. TP53 mutations are found in both entities and are therefore not discriminating. Differential diagnosis is important because the treatment will be that of the primary. Prognostic data for HCC revealed by bone metastasis are scarce, although they seem to be associated with a poor prognosis, with a 1 to 2 months overall survival. There is currently no data for hepatoid adenocarcinoma with bone metastasis.
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Affiliation(s)
- Sophie Neyrand
- Institut de pathologie multisite, centre de biologie et de pathologie Est, groupement hospitalier Est, hospices civils de Lyon, 59, boulevard Pinel, 69677 Bron, France
| | - Pierre-Paul Bringuier
- Institut de pathologie multisite, centre de biologie et de pathologie Est, groupement hospitalier Est, hospices civils de Lyon, 59, boulevard Pinel, 69677 Bron, France
| | - Nazim Benzerdjeb
- Institut de pathologie multisite - Site Sud, groupement hospitalier Sud, hospices civils de Lyon, Pierre-Bénite, France
| | - Valérie Hervieu
- Institut de pathologie multisite, centre de biologie et de pathologie Est, groupement hospitalier Est, hospices civils de Lyon, 59, boulevard Pinel, 69677 Bron, France
| | - Tanguy Fenouil
- Institut de pathologie multisite, centre de biologie et de pathologie Est, groupement hospitalier Est, hospices civils de Lyon, 59, boulevard Pinel, 69677 Bron, France.
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16
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Wang T, Li W, Wang Z, Wei X. A 47-year-old female with primary hepatoid adenocarcinoma in the pelvic retroperitoneum. Quant Imaging Med Surg 2023; 13:6317-6322. [PMID: 37711805 PMCID: PMC10498198 DOI: 10.21037/qims-22-1290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 07/31/2023] [Indexed: 09/16/2023]
Affiliation(s)
- Tao Wang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Department of Nuclear Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Weihua Li
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Zhenchang Wang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Xuan Wei
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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17
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Fei H, Li ZF, Chen YT, Zhao DB. Hepatoid adenocarcinoma of the stomach with neuroendocrine differentiation: A case report and review of literature. World J Clin Cases 2023; 11:5323-5331. [DOI: 10.12998/wjcc.v11.i22.5323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 06/24/2023] [Accepted: 07/17/2023] [Indexed: 08/03/2023] Open
Abstract
BACKGROUND Both hepatoid adenocarcinoma of the stomach (HAS) and neuroendocrine differentiation (NED) are rare histological subtypes of gastric cancer with unique clinicopathological features and unfavorable outcomes. HAS with NED is even rarer.
CASE SUMMARY Here, we report a 61-year-old man with HAS with NED, as detected by gastric wall thickening by positron emission tomography/computed tomography for a pulmonary nodule. Distal gastrectomy was performed, and pathological examination led to the diagnosis of HAS with NED. However, liver metastases occurred 6 mo later despite adjuvant chemotherapy, and the patient died 27 mo postoperatively.
CONCLUSION We treated a patient with HAS with NED who underwent adjuvant chemotherapy after radical surgery and still developed liver metastases. We first report the detailed processes of the treatment and development of HAS with NED, providing an important reference for the clinical diagnosis and treatment of this condition.
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Affiliation(s)
- He Fei
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ze-Feng Li
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ying-Tai Chen
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Dong-Bing Zhao
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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18
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Fei H, Li ZF, Chen YT, Zhao DB. Hepatoid adenocarcinoma of the stomach with neuroendocrine differentiation: A case report and review of literature. World J Clin Cases 2023; 11:5329-5337. [PMID: 37621602 PMCID: PMC10445072 DOI: 10.12998/wjcc.v11.i22.5329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 06/24/2023] [Accepted: 07/17/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND Both hepatoid adenocarcinoma of the stomach (HAS) and neuroendocrine differentiation (NED) are rare histological subtypes of gastric cancer with unique clinicopathological features and unfavorable outcomes. HAS with NED is even rarer. CASE SUMMARY Here, we report a 61-year-old man with HAS with NED, as detected by gastric wall thickening by positron emission tomography/computed tomography for a pulmonary nodule. Distal gastrectomy was performed, and pathological examination led to the diagnosis of HAS with NED. However, liver metastases occurred 6 mo later despite adjuvant chemotherapy, and the patient died 27 mo postoperatively. CONCLUSION We treated a patient with HAS with NED who underwent adjuvant chemotherapy after radical surgery and still developed liver metastases. We first report the detailed processes of the treatment and development of HAS with NED, providing an important reference for the clinical diagnosis and treatment of this condition.
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Affiliation(s)
- He Fei
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ze-Feng Li
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ying-Tai Chen
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Dong-Bing Zhao
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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19
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Dong C, Wang Y, Gu X, Lv X, Ren S, Wang Z, Dai Z. Differential diagnostic value of tumor markers and contrast-enhanced computed tomography in gastric hepatoid adenocarcinoma and gastric adenocarcinoma. Front Oncol 2023; 13:1222853. [PMID: 37538113 PMCID: PMC10396771 DOI: 10.3389/fonc.2023.1222853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 06/29/2023] [Indexed: 08/05/2023] Open
Abstract
Objective This study aimed to investigate the effectiveness of tumor markers and contrast-enhanced computed tomography (CE-CT) in differentiating gastric hepatoid adenocarcinoma (GHA) from gastric adenocarcinoma (GA). Methods This retrospective study included 160 patients (44 with GHA vs. 116 with GA) who underwent preoperative CE-CT. Preoperative serum concentrations of tumor biomarkers and CT imaging features were analyzed, including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), tumor location, growth pattern, size, enhancement pattern, cystic changes, and mass contrast enhancement. Multivariate logistic regression analyses were performed to evaluate useful tumor markers and CT imaging features for differentiating GHA from GA. Results When compared to GA, GHA showed a higher serum AFP [13.27 ng/ml (5.2-340.1) vs. 2.7 ng/ml (2.2-3.98), P <0.001] and CEA levels [4.07 ng/ml (2.73-12.53) vs. 2.42 ng/ml (1.38-4.31), P <0.001]. CT imaging showed GHA with a higher frequency of tumor location in the gastric antrum (P <0.001). GHA had significantly lower attenuation values at the portal venous phase [PCA, (82.34 HU ± 8.46 vs. 91.02 HU ± 10.62, P <0.001)] and delayed phase [DCA, (72.89 HU ± 8.83 vs. 78.27 HU ± 9.51, P <0.001)] when compared with GA. Multivariate logistic regression analyses revealed that tumor location, PCA, and serum AFP level were independent predictors of differentiation between GHA and GA. The combination of these three predictors performed well in discriminating GHA from GA, with an AUC of 0.903, a sensitivity of 86.36%, and a specificity of 81.90%. Conclusions Integrated evaluation of tumor markers and CT features, including tumor location, PCA, and serum AFP, allowed for more accurate differentiation of GHA from GA.
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Affiliation(s)
- Congsong Dong
- Department of Radiology, Affiliated Hospital 6 of Nantong University (Yancheng Third People’s Hospital), Yancheng, China
| | - Yanling Wang
- Department of Radiology, The People’s Hospital of Suzhou New District, Suzhou, China
| | - Xiaoyu Gu
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiaojing Lv
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Shuai Ren
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhongqiu Wang
- Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhenyu Dai
- Department of Radiology, Affiliated Hospital 6 of Nantong University (Yancheng Third People’s Hospital), Yancheng, China
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20
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Li L, Yang X, Ji W, Zhu Q, Yang X, Niu J, Li W. Emphasis on the clinical relationship between alpha-fetoprotein and hepatoid adenocarcinoma of the stomach: a retrospective study. BMC Gastroenterol 2023; 23:142. [PMID: 37161409 PMCID: PMC10170827 DOI: 10.1186/s12876-023-02773-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Accepted: 04/19/2023] [Indexed: 05/11/2023] Open
Abstract
BACKGROUND Hepatoid adenocarcinoma of the stomach (HAS) is a highly malignant and rare extrahepatic tumor. The prognosis is controversial because of its rarity and the lack of multi-center cohort studies, especially on the influence of serum Alpha-fetoprotein (AFP) level on prognosis. We aimed to analyze the clinicopathological characteristics and prognosis of HAS, particularly the effect of serum AFP on the prognosis of HAS. METHODS We retrospectively reviewed clinical data of one HAS patient treated at our institution in 2019 and of 252 patients reported between 1984 and 2020 in research databases. RESULTS Among these patients, 60.1% were > 60 years, 51% had lesions in the gastric antrum, and 51.0% (73/143) had the ulcerative lesion type. The preoperative elevated levels of serum alpha-fetoprotein (AFP) were detected in most patients (76.7%). Lymph-node (84.6%) and preoperative liver metastasis (39.1%) were often found. The high-AFP group was characterized by a higher rate of stage IV (P = 0.000682) and liver metastasis (P = 0.000068). The 1-, 3-and 5-year progression-free survival(PFS) rates were 41%, 18%, and 0%, and the 1-, 3-, and 5-year overall survival (OS) rates were 64%, 26%, and 21%, respectively. The survival analysis showed that OS was significantly shorter for HAS with high-AFP (> 300 ng/ml) than with low-AFP (≤ 300 ng/ml) (P = 0.023). The univariate analysis indicated that the OS of HAS was associated with tumor location, pTNM stage, lymph-node metastasis, surgical resection, and serum AFP > 300 ng/ml. However,the prognostic factors for PFS was only pTNM stage and surgical resection. The multivariate analysis confirmed that the independent prognostic factor affecting OS of HAS included pTNM stage and surgical resection. CONCLUSIONS Liver metastasis was increasingly more likely with increasingly higher serum AFP, but the prognosis of HAS is not necessarily poor. Serum AFP level is an important prognostic indicator in HAS and should be monitored.
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Affiliation(s)
- Lamei Li
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, N0.157 Xiwu Road,New Urban District, Xi'an, Shanxi Province, 710004, China
| | - Xinle Yang
- Department of Hepatology, First Hospital, Jilin University, N0.71 Xinmin Street,Chaoyang District, Changchun, 130021, Jilin Provinice, China
| | - Wei Ji
- Department of Oncology, First Hospital, Jilin University, N0.71 Xinmin Street,Chaoyang District, Changchun, 130021, Jilin Provinice, China
| | - Qi Zhu
- Department of Hepatology, First Hospital, Jilin University, N0.71 Xinmin Street,Chaoyang District, Changchun, 130021, Jilin Provinice, China
| | - Xin Yang
- Department of Hepatology, First Hospital, Jilin University, N0.71 Xinmin Street,Chaoyang District, Changchun, 130021, Jilin Provinice, China
| | - Junqi Niu
- Department of Hepatology, First Hospital, Jilin University, N0.71 Xinmin Street,Chaoyang District, Changchun, 130021, Jilin Provinice, China
| | - Wanyu Li
- Department of Hepatology, First Hospital, Jilin University, N0.71 Xinmin Street,Chaoyang District, Changchun, 130021, Jilin Provinice, China.
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Li M, Mei YX, Wen JH, Jiao YR, Pan QR, Kong XX, Li J. Hepatoid adenocarcinoma-Clinicopathological features and molecular characteristics. Cancer Lett 2023; 559:216104. [PMID: 36863507 DOI: 10.1016/j.canlet.2023.216104] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 01/17/2023] [Accepted: 02/20/2023] [Indexed: 03/04/2023]
Abstract
Hepatoid adenocarcinoma (HAC) is a rare, malignant, extrahepatic tumor with histologic features similar to those of hepatocellular carcinoma. HAC is most often associated with elevated alpha-fetoprotein (AFP). HAC can occur in multiple organs, including the stomach, esophagus, colon, pancreas, lungs, and ovaries. HAC differs greatly from typical adenocarcinoma in terms of its biological aggression, poor prognosis, and clinicopathological characteristics. However, the mechanisms underlying its development and invasive metastasis remain unclear. The purpose of this review was to summarize the clinicopathological features, molecular traits, and molecular mechanisms driving the malignant phenotype of HAC, in order to support the clinical diagnosis and treatment of HAC.
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Affiliation(s)
- Ming Li
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Clinical Research Center for Cancer, China; Cancer Center of Zhejiang University, China
| | - Yan-Xia Mei
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Clinical Research Center for Cancer, China; Cancer Center of Zhejiang University, China
| | - Ji-Hang Wen
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Clinical Research Center for Cancer, China; Cancer Center of Zhejiang University, China
| | - Yu-Rong Jiao
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Clinical Research Center for Cancer, China; Cancer Center of Zhejiang University, China
| | - Qiang-Rong Pan
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Clinical Research Center for Cancer, China; Cancer Center of Zhejiang University, China
| | - Xiang-Xing Kong
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Clinical Research Center for Cancer, China; Cancer Center of Zhejiang University, China.
| | - Jun Li
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Clinical Research Center for Cancer, China; Cancer Center of Zhejiang University, China.
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Bonis A, Dell’Amore A, Verzeletti V, Melan L, Zambello G, Nardocci C, Comacchio GM, Pezzuto F, Calabrese F, Rea F. Hepatoid Adenocarcinoma of the Lung: A Review of the Most Updated Literature and a Presentation of Three Cases. J Clin Med 2023; 12:jcm12041411. [PMID: 36835946 PMCID: PMC9964907 DOI: 10.3390/jcm12041411] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 02/03/2023] [Accepted: 02/09/2023] [Indexed: 02/12/2023] Open
Abstract
In a Surgical Thoracic Center, two females and a man were unexpectedly diagnosed with hepatoid adenocarcinoma of the lung (HAL) in a single year. HAL is a rare lung cancer with pathological features of hepatocellular carcinoma with no evidence of liver tumor or other primitive sites of neoplasms. As of today, a comprehensive treatment is still not written. We reviewed the most updated literature on HAL, aiming to highlight the proposed treatments available, and comparing them in terms of survival. General hallmarks of HAL are confirmed: it typically affects middle-aged, heavy-smoker males with a median of 5 cm bulky right upper lobe mass. Overall survival remains poor (13 months), with a longer but non-significant survival in females. Treatments are still unsatisfactory today: surgery guarantees a small benefit compared to non-operated HALs, and only N0 patients demonstrated improved survival (p = 0.04) compared to N1, N2, and N3. Even though the histology is fearsome, these are probably the patients who will benefit from upfront surgery. Chemotherapy seemed to behave as surgery, and there is no statistical difference between chemotherapy only, surgery, or adjuvant treatments, even though adjuvant treatments tend to be more successful. New chemotherapies have been reported with notable results in recent years, such as Tyrosine Kinase Inhibitors and monoclonal antibodies. In this complicated picture, new cases are needed to further build shared evidence in terms of diagnosis, treatments, and survival opportunities.
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Affiliation(s)
- Alessandro Bonis
- Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health–DSCTV, University of Padova, 35122 Padova, Italy
| | - Andrea Dell’Amore
- Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health–DSCTV, University of Padova, 35122 Padova, Italy
- Correspondence: ; Tel.: +39-0498-218-740
| | - Vincenzo Verzeletti
- Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health–DSCTV, University of Padova, 35122 Padova, Italy
| | - Luca Melan
- Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health–DSCTV, University of Padova, 35122 Padova, Italy
| | - Giovanni Zambello
- Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health–DSCTV, University of Padova, 35122 Padova, Italy
| | - Chiara Nardocci
- Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health–DSCTV, University of Padova, 35122 Padova, Italy
| | - Giovanni Maria Comacchio
- Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health–DSCTV, University of Padova, 35122 Padova, Italy
| | - Federica Pezzuto
- Pathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health–DSCTV, University of Padova, 35122 Padova, Italy
| | - Fiorella Calabrese
- Pathology Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health–DSCTV, University of Padova, 35122 Padova, Italy
| | - Federico Rea
- Thoracic Surgery Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health–DSCTV, University of Padova, 35122 Padova, Italy
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23
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Yang Q, Liu Y, Zhang S. Hepatoid adenocarcinoma of the stomach: CT findings. Front Oncol 2023; 13:1036763. [PMID: 36816961 PMCID: PMC9937653 DOI: 10.3389/fonc.2023.1036763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 01/23/2023] [Indexed: 02/05/2023] Open
Abstract
Objective To analyze the CT findings of hepatoid adenocarcinoma of the stomach (HAS) and improve the diagnosis accuracy of this condition. Methods The CT images of 22 pathologically confirmed HAS patients were analyzed retrospectively. We investigated the location of lesions, morphology, enhancement features, area of invasion into surrounding organs, lymph node metastasis, and venous tumor thrombus. Results Among the 22 patients (17 men and 5 women, the mean age was 61.41 ± 9.83 years ranging from 36 to 80 years) with HAS; the morphology of tumors included mass (n = 5), focal ulcer (n = 7), and infiltrating ulcer (n = 10). Extraserous fat was invaded in 12 cases. Enhancement scans showed continuous enhancement in all cases. The CT values of unenhanced scan, the arterial phase, and the portal venous phase are 30.36 ± 6.46, 60.91 ± 17.80, and 75.64 ± 22.09 (Hounsfield Unit, HU), respectively. In six cases, the tumor infiltrated the surrounding organs: liver (n = 1), pancreas (n = 2), and both liver and pancreas (n = 3). In 16 out of 22 patients (72.3%), suspicious lymph node metastasis at CT imaging has then been confirmed by pathological specimens. Intrahepatic metastasis was found in 14 cases. Seven patients had venous tumor thrombus: three patients developed tumor thrombus in the main trunk and intrahepatic branches of the portal vein and two patients in the portal vein, splenic vein, and superior mesenteric vein simultaneously. Conclusion The CT scans of HAS often show a thickened gastric wall and infiltrating ulceration. Infiltration into extraserosal fat is often seen. Enhancement scans show a continuous and progressive enhancement of lesions. Lymph node metastasis, intrahepatic metastasis, and portal vein tumor thrombus are common in HAS patients.
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Affiliation(s)
- Qian Yang
- *Correspondence: Qian Yang, ; Yulin Liu, ; Shuixia Zhang,
| | - Yulin Liu
- *Correspondence: Qian Yang, ; Yulin Liu, ; Shuixia Zhang,
| | - Shuixia Zhang
- *Correspondence: Qian Yang, ; Yulin Liu, ; Shuixia Zhang,
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24
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Mattiolo P, Scarpa A, Luchini C. Hepatoid tumors of the gastrointestinal/pancreatobiliary district: morphology, immunohistochemistry, and molecular profiles. Hum Pathol 2023; 132:169-175. [PMID: 35714834 DOI: 10.1016/j.humpath.2022.06.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 06/08/2022] [Indexed: 02/07/2023]
Abstract
Hepatoid tumors (HTs) histologically resemble hepatocellular carcinoma (HCC) but manifest outside the liver. Regarding immunohistochemistry (IHC), the classical markers of hepatoid differentiation are Hep Par-1, CD10, and arginase-1. This study provides a critical overview of HT in the gastrointestinal/biliopancreatic system, which is the most common site of origin. Gastric HTs are malignant neoplasms recognized by the current WHO classification as a variant of adenocarcinoma. In addition to the classic IHC markers, SALL4 and claudin-6 can help exclude a metastatic HCC at this site. Next-generation sequencing revealed the most common alterations, including TP53 mutation, microsatellite instability (MSI), and Her2 amplification. Esophageal HTs are exceptionally rare and usually arise in the context of Barrett's esophagus. In the intestine, HTs are classified within the adenocarcinoma spectrum and manifest more often in the background of inflammatory bowel disease. Regarding their molecular profile, recurrent alterations included MSI and NCOA4-RET fusions. In the pancreas, the current WHO classification acknowledges HT only as a possible variant of ductal adenocarcinoma, characterized by a poor prognosis. However, at this site, neuroendocrine tumors (NETs) and solid pseudopapillary neoplasms (SPNs) may also show hepatoid differentiation. Hepatoid NETs show aggressive behavior, whereas hepatoid SPNs harbor CTNNB1 mutations and are characterized by an indolent clinical course. Lastly, biliary HTs belong to the adenocarcinoma category and usually show a poor prognosis. In conclusion, gastrointestinal/pancreatobiliary HTs show specific histomolecular features, which should be considered for improving routine diagnostic activity and clinical management.
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Affiliation(s)
- Paola Mattiolo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, 37134, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, 37134, Italy; ARC-Net Research Center for Applied Research on Cancer, University of Verona, Verona, 37134, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, 37134, Italy; ARC-Net Research Center for Applied Research on Cancer, University of Verona, Verona, 37134, Italy.
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25
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Wang J, Kang B, Sun C, Du F, Lin J, Ding F, Dai Z, Zhang Y, Yang C, Shang L, Li L, Hong Q, Huang C, Wang G. CT-based radiomics nomogram for differentiating gastric hepatoid adenocarcinoma from gastric adenocarcinoma: a multicentre study. Expert Rev Gastroenterol Hepatol 2023; 17:205-214. [PMID: 36625225 DOI: 10.1080/17474124.2023.2166490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND To develop a CT-based radiomics nomogram for the high-precision preoperative differentiation of gastric hepatoid adenocarcinoma (GHAC) patients from gastric adenocarcinoma (GAC) patients. RESEARCH DESIGN AND METHODS 108 patients with GHAC from 6 centers and 108 GAC patients matched by age, sex and T stage undergoing pathological examination were retrospectively reviewed. Patients from 5 centers were divided into two cohorts (training and internal validation) at a 7:3 ratio, the remaining patients were external test cohort. Venous-phase CT images were retrieved for tumor segmentation and feature extraction. A radiomics model was developed by the least absolute shrinkage and selection operator method. The nomogram was developed by clinical factors and the radiomics score. RESULTS 1409 features were extracted and a radiomics model consisting of 19 features was developed, which showed a favorable performance in discriminating GHAC from GAC (AUCtraining cohort = 0.998, AUCinternal validation set = 0.942, AUCexternal test cohort = 0.731). The radiomics nomogram, including the radiomics score, AFP, and CA72_4, achieved good calibration and discrimination (AUCtraining cohort = 0.998, AUCinternal validation set = 0.954, AUCexternal test cohort = 0.909). CONCLUSIONS The noninvasive CT-based nomogram, including radiomics score, AFP, and CA72_4, showed favorable predictive efficacy for differentiating GHAC from GAC and might be useful for clinical decision-making.
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Affiliation(s)
- Jing Wang
- Department of Radiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
| | - Bing Kang
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Cong Sun
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Fengying Du
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Jianxian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Fanghui Ding
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Zhengjun Dai
- Scientific Research Department, Huiying Medical Technology Co., Ltd,Beijing, China
| | - Yifei Zhang
- Department of Gastrointestinal Surgery, Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University, Yantai, Shandong, China
| | - Chenggang Yang
- Department of Gastrointestinal Surgery, Liaocheng people's hospital, Liaocheng, Shandong, China
| | - Liang Shang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Leping Li
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Qingqi Hong
- Department of Gastrointestinal Oncology Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.,The School of Clinical Medicine, Fujian Medical University, The Graduate School of Fujian Medical University, Xiamen, Fujian, China
| | - Changming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Guangbin Wang
- Department of Radiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.,Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
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Yang X, Wang A, Li J, Zhou K, Ji K, Ji X, Zhang J, Wu X, Bu Z. Prognostic significance of preoperative serum tumor markers in hepatoid adenocarcinoma of stomach (HAS). BMC Cancer 2023; 23:53. [PMID: 36647059 PMCID: PMC9841701 DOI: 10.1186/s12885-023-10516-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Accepted: 01/05/2023] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND The role of preoperative serum tumor markers in HAS patients was vague, we designed the study to explore the effect of preoperative serum tumor markers on predicting the prognosis of HAS patients. METHODS A total of 139 patients were included according to the different tumor makers. X-tile tool was employed to identify the optimal cut-off values of respective tumor makers. Multivariate analyses were conducted to determine independent risk factors. RESULTS The optimal cut-off value of alpha-fetoprotein (AFP) for 3-years overall survival (OS) and recurrence-free survival (RFS) was 516 ng/mL. Patients with high-level AFP values assumed significantly worse OS and RFS than those with low-level AFP values (P = 0.028 and P = 0.011, respectively). The optimal cut-off value of Carbohydrate antigen (CA)19-9 for OS and RFS was 51.3 U/mL. And the survival results were similar with AFP in the aspects of OS and RFS (P = 0.009 and P < 0.001, respectively). Multivariate analyses showed that high serum AFP was an independent risk factor for OS and RFS of HAS patients (HR7.264; 95% CI 1.328-39.738; P = 0.022 and HR 2.688; 95% CI 0.922-7.836; P = 0.070, respectively). CA19-9 could perform as a fair substitute to predict the HAS patients' OS and RFS when the preoperative serum AFP was unavailable (HR 7.816; 95% CI 2.084-29.308; P = 0.002 and HR 4.386; 95% CI 1.824-10.547; P = 0.001, respectively). Other tumor markers didn't present significant influences. CONCLUSIONS Applying preoperative serum AFP level to predict the HAS patients' prognosis is feasible and preoperative serum high-AFP is an independent risk factor for OS and RFS of HAS patients. Preoperative serum CA19-9 could be an alternative choice when AFP was absent.
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Affiliation(s)
- Xuesong Yang
- grid.412474.00000 0001 0027 0586Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute, Beijing, China
| | - Anqiang Wang
- grid.412474.00000 0001 0027 0586Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute, Beijing, China
| | - Jialin Li
- grid.412474.00000 0001 0027 0586Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute, Beijing, China
| | - Kai Zhou
- grid.412474.00000 0001 0027 0586Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute, Beijing, China
| | - Ke Ji
- grid.412474.00000 0001 0027 0586Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xin Ji
- grid.412474.00000 0001 0027 0586Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute, Beijing, China
| | - Ji Zhang
- grid.412474.00000 0001 0027 0586Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiaojiang Wu
- grid.412474.00000 0001 0027 0586Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zhaode Bu
- grid.412474.00000 0001 0027 0586Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute, Beijing, China
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Wu X, Di L, Li C, Zhang S, Tan N, Huang J, Tuo B. Early hepatoid adenocarcinoma of the stomach with signet ring cell carcinoma: A case report and clinicopathological features. Front Oncol 2023; 12:1016447. [PMID: 36713511 PMCID: PMC9874694 DOI: 10.3389/fonc.2022.1016447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 12/22/2022] [Indexed: 01/12/2023] Open
Abstract
Background Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer with poor prognosis, and its clinicopathological features are not well understood, so the pathology from the clinical biopsy is easily misdiagnosed, especially for special or atypical HAS. We present an extremely rare early HAS with signet ring cell carcinoma and evaluate its clinicopathological features. Case presentation A 51-year-old female patient of Chinese Han ethnicity with upper abdominal pain for 5 years and worsened abdominal pain for 1 month was admitted to our hospital. Esophagogastroduodenoscopy showed a submucosal tumor-like elevated lesion with central depression in the greater curvature of the junction between the antrum and body. Histopathological examination from the biopsy revealed medium-low-differentiation adenocarcinoma with signet ring cell carcinoma. Radical gastrectomy was performed, and the final diagnosis was early HAS with signet ring cell carcinoma. Conclusions HAS with signet ring cell carcinoma is a special type of HAS and extremely rare. It is first presented for this extremely rare type of HAS, which contributes to strengthen the understanding for the clinicopathological characteristics of HAS and especially promote early detection of HAS.
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Affiliation(s)
- Xinglong Wu
- Department of Pathology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Lianjun Di
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Chengfang Li
- Department of Pathology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Suyuan Zhang
- Department of Pathology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Na Tan
- Department of Pathology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Jiajia Huang
- Department of Pathology, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Biguang Tuo
- Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China,*Correspondence: Biguang Tuo,
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Zhou Y, Dong L, Dai L, Hu S, Sun Y, Wu Y, Pan T, Li X. Pathologic complete response of hepatoid adenocarcinoma of the stomach after chemo-immunotherapy: A rare case report and literature review. Front Surg 2023; 10:1133335. [PMID: 37065996 PMCID: PMC10098014 DOI: 10.3389/fsurg.2023.1133335] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 03/13/2023] [Indexed: 04/18/2023] Open
Abstract
Background Hepatoid adenocarcinoma of the stomach (HAS) is a highly malignant subtype of gastric carcinoma with specific clinicopathological features and extremely poor prognosis. We present an exceedingly rare case of complete response after chemo-immunotherapy. Case Description A 48-year-old woman with highly elevated serum alpha-fetoprotein (AFP) level was found to have HAS verified by pathological examination based on gastroscopy. Computed tomography scan was done and TNM staging of the tumor was T4aN3aMx. Programmed cell death ligand-1 (PD-L1) immunohistochemistry was performed, revealing a negative PD-L1 expression. Chemo-immunotherapy including oxaliplatin plus S-1 and PD-1 inhibitor terelizumab was given to this patient for 2 months until the serum AFP level decreased from 748.5 to 12.9 ng/mL and the tumor shrank. D2 radical gastrectomy was then performed and histopathology of the resected specimen revealed that the cancerous cells had disappeared. Pathologic complete response (pCR) was achieved and no evidence of recurrence has been found after 1 year of follow-up. Conclusions We, for the first time, reported an HAS patient with negative PD-L1 expression who achieved pCR from the combined chemotherapy and immunotherapy. Although no consensus has been reached regarding the therapy, it might provide a potential effective management strategy for HAS patient.
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Affiliation(s)
- Yunxiang Zhou
- Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China
| | - Linping Dong
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
- Department of Surgery, Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Linyun Dai
- Department of Surgery, Haiyan People's Hospital, Jiaxing, Zhejiang, China
| | - Sien Hu
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
| | - Yongji Sun
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
| | - Yulian Wu
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
- Department of Surgery, Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Tao Pan
- Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China
- Correspondence: Tao Pan Xiawei Li
| | - Xiawei Li
- Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China
- Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
- Correspondence: Tao Pan Xiawei Li
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Kamiimabeppu D, Wakatsuki T, Takahari D, Fukuda N, Shimozaki K, Osumi H, Nakayama I, Ogura M, Ooki A, Shinozaki E, Chin K, Yamaguchi K. Treatment efficacy of ramucirumab-containing chemotherapy in patients with alpha-fetoprotein producing gastric cancer. Int J Clin Oncol 2023; 28:121-129. [PMID: 36409433 DOI: 10.1007/s10147-022-02263-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 10/30/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Alpha-Fetoprotein Producing Gastric Cancer (AFPGC) is an aggressive subgroup of gastric cancer. Recently ramucirumab has shown survival benefits in hepatocellular carcinoma, but only in those with higher Alpha-Fetoprotein (AFP) levels. However, the efficacy of ramucirumab-containing chemotherapy in AFPGC remains unclear. METHODS We retrospectively assessed 352 patients who received ramucirumab-containing chemotherapy between June 2015 and December 2019. AFPGC was defined when serum AFP levels were elevated at diagnosis and correlated with the disease state during treatment. Non-AFPGC was defined when serum AFP levels were normal at diagnosis. RESULTS Among the 352 patients, 28 patients were defined as AFPGC and 246 patients were defined as non-AFPGC. AFPGC was characterized by high frequency of liver metastasis and low frequency of peritoneal metastasis compared to non-AFPGC. Ramucirumab containing chemotherapy showed higher response rates in AFPGC (39.1% vs 24.8%, p = 0.198) and disease control rates (86.9% vs 61.5%, p = 0.028) than those of non-AFPGC, respectively. Median progression-free survival (PFS) was 5.5 months (95%CI 3.9-7.1) in AFPGC and 4.0 months (95%CI 3.6-4.6) in non-AFPGC (HR: 0.91, 95% CI 0.61-1.36, p = 0.66), and median overall survival (OS) was 10.7 months (95% CI 7.4-20.8) in AFPGC and 9.2 months (95% CI 8.1-10.4) in non-AFPGC (HR: 0.72, 95% CI 0.48-1.08, p = 0.11), respectively. In multivariate analysis, AFPGC was not a negative prognostic factor both for PFS and OS. CONCLUSION Ramucirumab containing chemotherapy showed higher response and comparable survival in AFPGC compared to those of non-AFPGC. Considering the generally poor prognosis of AFPGC, ramucirumab-containing chemotherapy might be a promising treatment option in AFPGC.
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Affiliation(s)
- Daisaku Kamiimabeppu
- Department of Gastrointestinal Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake Koto-ku, Tokyo, 135-8550, Japan
| | - Takeru Wakatsuki
- Department of Gastrointestinal Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake Koto-ku, Tokyo, 135-8550, Japan.
| | - Daisuke Takahari
- Department of Gastrointestinal Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake Koto-ku, Tokyo, 135-8550, Japan
| | - Naoki Fukuda
- Department of Gastrointestinal Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake Koto-ku, Tokyo, 135-8550, Japan
| | - Keitaro Shimozaki
- Department of Gastrointestinal Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake Koto-ku, Tokyo, 135-8550, Japan
| | - Hiroki Osumi
- Department of Gastrointestinal Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake Koto-ku, Tokyo, 135-8550, Japan
| | - Izuma Nakayama
- Department of Gastrointestinal Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake Koto-ku, Tokyo, 135-8550, Japan
| | - Mariko Ogura
- Department of Gastrointestinal Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake Koto-ku, Tokyo, 135-8550, Japan
| | - Akira Ooki
- Department of Gastrointestinal Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake Koto-ku, Tokyo, 135-8550, Japan
| | - Eiji Shinozaki
- Department of Gastrointestinal Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake Koto-ku, Tokyo, 135-8550, Japan
| | - Keisho Chin
- Department of Gastrointestinal Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake Koto-ku, Tokyo, 135-8550, Japan
| | - Kensei Yamaguchi
- Department of Gastrointestinal Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake Koto-ku, Tokyo, 135-8550, Japan
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30
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Yao Y, Liu K, Wu Y, Zhou J, Jin H, Zhang Y, Zhu Y. Comprehensive landscape of the functions and prognostic value of RNA binding proteins in uterine corpus endometrial carcinoma. Front Mol Biosci 2022; 9:962412. [PMID: 36262474 PMCID: PMC9574853 DOI: 10.3389/fmolb.2022.962412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 09/14/2022] [Indexed: 12/24/2022] Open
Abstract
Background: The dysregulation of RNA binding proteins (RBPs) is involved in tumorigenesis and progression. However, information on the overall function of RNA binding proteins in Uterine Corpus Endometrial Carcinoma (UCEC) remains to be studied. This study aimed to explore Uterine Corpus Endometrial Carcinoma-associated molecular mechanisms and develop an RNA-binding protein-associated prognostic model. Methods: Differently expressed RNA binding proteins were identified between Uterine Corpus Endometrial Carcinoma tumor tissues and normal tissues by R packages (DESeq2, edgeR) from The Cancer Genome Atlas (TCGA) database. Hub RBPs were subsequently identified by univariate and multivariate Cox regression analyses. The cBioPortal platform, R packages (ggplot2), Human Protein Atlas (HPA), and TIMER online database were used to explore the molecular mechanisms of Uterine Corpus Endometrial Carcinoma. Kaplan-Meier (K-M), Area Under Curve (AUC), and the consistency index (c-index) were used to test the performance of our model. Results: We identified 128 differently expressed RNA binding proteins between Uterine Corpus Endometrial Carcinoma tumor tissues and normal tissues. Seven RNA binding proteins genes (NOP10, RBPMS, ATXN1, SBDS, POP5, CD3EAP, ZC3H12C) were screened as prognostic hub genes and used to construct a prognostic model. Such a model may be able to predict patient prognosis and acquire the best possible treatment. Further analysis indicated that, based on our model, the patients in the high-risk subgroup had poor overall survival (OS) compared to those in the low-risk subgroup. We also established a nomogram based on seven RNA binding proteins. This nomogram could inform individualized diagnostic and therapeutic strategies for Uterine Corpus Endometrial Carcinoma. Conclusion: Our work focused on systematically analyzing a large cohort of Uterine Corpus Endometrial Carcinoma patients in the The Cancer Genome Atlas database. We subsequently constructed a robust prognostic model based on seven RNA binding proteins that may soon inform individualized diagnosis and treatment.
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Affiliation(s)
- Yong Yao
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- MOE Key Laboratory of Population Health Across Life Cycle, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, Hefei, Anhui, China
| | - Kangping Liu
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- MOE Key Laboratory of Population Health Across Life Cycle, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, Hefei, Anhui, China
| | - Yuxuan Wu
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- MOE Key Laboratory of Population Health Across Life Cycle, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, Hefei, Anhui, China
| | - Jieyu Zhou
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- MOE Key Laboratory of Population Health Across Life Cycle, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, Hefei, Anhui, China
| | - Heyue Jin
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- MOE Key Laboratory of Population Health Across Life Cycle, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, Hefei, Anhui, China
| | - Yimin Zhang
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- MOE Key Laboratory of Population Health Across Life Cycle, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, Hefei, Anhui, China
| | - Yumin Zhu
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- MOE Key Laboratory of Population Health Across Life Cycle, Hefei, Anhui, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, Hefei, Anhui, China
- *Correspondence: Yumin Zhu,
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Jiang J, Ding Y, Lu J, Chen Y, Chen Y, Zhao W, Chen W, Kong M, Li C, Teng X, Zhou Q, Xu N, Zhou D, Zhou Z, Wang H, Teng L. Integrative analysis reveals a clinicogenomic landscape associated with liver metastasis and poor prognosis in hepatoid adenocarcinoma of the stomach. Int J Biol Sci 2022; 18:5554-5574. [PMID: 36147475 PMCID: PMC9461653 DOI: 10.7150/ijbs.71449] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 08/20/2022] [Indexed: 12/02/2022] Open
Abstract
Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC) that histologically resembles hepatocellular carcinoma (HCC). Despite its low incidence, HAS had a poor 5-year survival rate. Currently, the linkages between clinicopathological and genomic features of HAS and its therapeutic targets remain largely unknown. Herein, we enrolled 90 HAS patients and 270 stage-matched non-HAS patients from our institution for comparing clinicopathological features. We found that HAS had worse overall survival and were more prone to develop liver metastasis than non-HAS in our cohort, which was validated via meta-analysis. By comparing whole-exome sequencing data of HAS (n=30), non-HAS (n=63), and HCC (n=355, The Cancer Genome Atlas), we identified a genomic landscape associated with unfavorable clinical features in HAS, which contained frequent somatic mutations and widespread copy number variations. Notably, signaling pathways regulating pluripotency of stem cells affected by frequent genomic alterations might contribute to liver metastasis and poor prognosis in HAS patients. Furthermore, HAS developed abundant multiclonal architecture associated with liver metastasis. Encouragingly, target analysis suggested that HAS patients might potentially benefit from anti-ERBB2 or anti-PD-1 therapy. Taken together, this study systematically demonstrated a high risk of liver metastasis and poor prognosis in HAS, provided a clinicogenomic landscape underlying these unfavorable clinical features, and identified potential therapeutic targets, laying the foundations for developing precise diagnosis and therapy in this rare but lethal disease.
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Affiliation(s)
- Junjie Jiang
- Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yongfeng Ding
- Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jun Lu
- Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yanyan Chen
- Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yiran Chen
- Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wenyi Zhao
- Institute of Drug Metabolism & Pharmaceutical Analysis & Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Wenfan Chen
- Institute of Drug Metabolism & Pharmaceutical Analysis & Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Mei Kong
- Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Chengzhi Li
- Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaodong Teng
- Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Quan Zhou
- Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China
| | - Nong Xu
- Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Donghui Zhou
- Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhan Zhou
- Institute of Drug Metabolism & Pharmaceutical Analysis & Zhejiang Provincial Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Haiyong Wang
- Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lisong Teng
- Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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32
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Zhao R, Li H, Ge W, Zhu X, Zhu L, Wan X, Wang G, Pan H, Lu J, Han W. Comprehensive Analysis of Genomic Alterations in Hepatoid Adenocarcinoma of the Stomach and Identification of Clinically Actionable Alterations. Cancers (Basel) 2022; 14:cancers14163849. [PMID: 36010842 PMCID: PMC9405706 DOI: 10.3390/cancers14163849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 07/30/2022] [Accepted: 08/02/2022] [Indexed: 11/25/2022] Open
Abstract
Simple Summary Hepatoid adenocarcinoma of the stomach (HAS) is a subset of gastric cancer (GC) histologically characterized by hepatocellular carcinoma-like foci with or without alpha-fetoprotein secretion, which is easily misdiagnosed. Genomic alterations and potential targets for this population are still largely unknown. Additionally, treatment regimens of HAS are mainly based on GC guidelines, which is not reasonable for diseases with great heterogeneity. The present study comprehensively depicts the genomic features of HAS, and they are significantly different from GC, AFP-producing GC (AFPGC), and liver hepatocellular carcinoma (LIHC). Multiple aggressive behavior-related amplificated or deleted regions in HAS are firstly reported. Moreover, reliable and practicable clinically actionable alterations for HAS are identified, providing evidence for making personalized therapy based on the genomic characteristics of HAS instead of GC. Abstract Hepatoid adenocarcinoma of the stomach (HAS) is a rare malignancy with aggressive biological behavior. This study aimed to compare the genetic landscape of HAS with liver hepatocellular carcinoma (LIHC), gastric cancer (GC), and AFP-producing GC (AFPGC) and identify clinically actionable alterations. Thirty-eight cases of HAS were collected for whole-exome sequencing. Significantly mutated genes were identified. TP53 was the most frequently mutated gene (66%). Hypoxia, TNF-α/NFκB, mitotic spindle assembly, DNA repair, and p53 signaling pathways mutated frequently. Mutagenesis mechanisms in HAS were associated with spontaneous or enzymatic deamination of 5-methylcytosine to thymine and defective homologous recombination-related DNA damage repair. However, LIHC was characteristic of exposure to aflatoxin and aristolochic acid. The copy number variants (CNVs) in HAS was significantly different compared to LIHC, GC, and AFPGC. Aggressive behavior-related CNVs were identified, including local vascular invasion, advanced stages, and adverse prognosis. In 55.26% of HAS patients there existed at least one clinically actionable alteration, including ERBB2, FGFR1, CDK4, EGFR, MET, and MDM2 amplifications and BRCA1/2 mutations. MDM2 amplification with functional TP53 was detected in 5% of HAS patients, which was proved sensitive to MDM2 inhibitors. A total of 10.53% of HAS patients harbored TMB > 10 muts/Mb. These findings improve our understanding of the genomic features of HAS and provide potential therapeutic targets.
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Affiliation(s)
- Rongjie Zhao
- Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
| | - Hongshen Li
- Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
| | - Weiting Ge
- Cancer Institute, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310005, China
| | - Xiuming Zhu
- Department of Medical Oncology, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou 314408, China
| | - Liang Zhu
- Department of Pathology, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou 310005, China
| | - Xiangbo Wan
- Department of Radical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 518052, China
| | - Guanglan Wang
- Department of Pathology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
| | - Hongming Pan
- Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
| | - Jie Lu
- Department of Gastroenterology, Gongli Hospital of Shanghai Pudong New Area, Shanghai University, Shanghai 200135, China
- Department of Gastroenterology, The Tenth People’s Hospital of Tongji University, Shanghai 311202, China
- Correspondence: (J.L.); (W.H.)
| | - Weidong Han
- Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China
- Correspondence: (J.L.); (W.H.)
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Mattiolo P, Mafficini A, Lawlor RT, Marchegiani G, Malleo G, Pea A, Salvia R, Piccoli P, Sciammarella C, Santonicco N, Parisi A, Silvestris N, Milella M, Adsay V, Scarpa A, Luchini C. "Pure" hepatoid tumors of the pancreas harboring CTNNB1 somatic mutations: a new entity among solid pseudopapillary neoplasms. Virchows Arch 2022; 481:41-47. [PMID: 35359182 PMCID: PMC9226109 DOI: 10.1007/s00428-022-03317-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 03/04/2022] [Accepted: 03/26/2022] [Indexed: 02/06/2023]
Abstract
Hepatoid tumors (HTs) represent a rare group of neoplasms that are histologically similar to hepatocellular carcinoma but arise outside the liver. The current World Health Organization classification recognizes the hepatoid morphology of pancreatic tumors only as a possible variant of pancreatic ductal adenocarcinoma (PDAC). Here, we describe two cases of "pure" HT of the pancreas showing common features and characterized by indolent biological behavior. These tumors were roundish nodules with pushing borders, hyaline globules, and pure hepatoid histology; they were diffusely positive for β-catenin and LEF1 on immunohistochemistry. At next-generation sequencing, both neoplasms harbored only one pathogenic somatic mutation that affected the CTNNB1 gene at exon 3 and showed a loss of heterozygosity on chromosomes 18 and 21. By integrating macroscopic and microscopic features, along with their molecular profiles, we advocate that such tumors represent a distinct entity from PDAC and should be considered a new variant of solid pseudopapillary neoplasms. The recognition of this new neoplastic category may have immediate implications not only for tumor taxonomy but also for clinical practice.
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Affiliation(s)
- Paola Mattiolo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Piazzale Scuro, 10, 37134, Verona, Italy
| | - Andrea Mafficini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Piazzale Scuro, 10, 37134, Verona, Italy
| | - Rita T Lawlor
- ARC-Net Research Center for Applied Research On Cancer, University of Verona, 37134, Verona, Italy
| | - Giovanni Marchegiani
- Department of Surgery, The Pancreas Institute, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Giuseppe Malleo
- Department of Surgery, The Pancreas Institute, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Antonio Pea
- Department of Surgery, The Pancreas Institute, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Roberto Salvia
- Department of Surgery, The Pancreas Institute, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Paola Piccoli
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Piazzale Scuro, 10, 37134, Verona, Italy
| | - Concetta Sciammarella
- ARC-Net Research Center for Applied Research On Cancer, University of Verona, 37134, Verona, Italy
| | - Nicola Santonicco
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Piazzale Scuro, 10, 37134, Verona, Italy
| | - Alice Parisi
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Piazzale Scuro, 10, 37134, Verona, Italy
| | - Nicola Silvestris
- Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, 98125, Messina, Italy
| | - Michele Milella
- Department of Medicine, Section of Medical Oncology, University and Hospital Trust of Verona, 37134, Verona, Italy
| | - Volkan Adsay
- Department of Pathology, Koç University Hospital and Koç University Research Center for Translational Medicine (KUTTAM), 34010, Istanbul, Turkey
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Piazzale Scuro, 10, 37134, Verona, Italy
- ARC-Net Research Center for Applied Research On Cancer, University of Verona, 37134, Verona, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Piazzale Scuro, 10, 37134, Verona, Italy.
- ARC-Net Research Center for Applied Research On Cancer, University of Verona, 37134, Verona, Italy.
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Liu M, Luo C, Xie ZZ, Li X. Treatment of gastric hepatoid adenocarcinoma with pembrolizumab and bevacizumab combination chemotherapy: A case report. World J Clin Cases 2022; 10:5420-5427. [PMID: 35812689 PMCID: PMC9210915 DOI: 10.12998/wjcc.v10.i16.5420] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 12/19/2021] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gastric hepatoid adenocarcinoma (GHA) is a rare and aggressive cancer that is characterized by foci with features of both hepatocellular differentiation and adenomatous differentiation. However, there is currently no standard treatment for this disease, which has a poor prognosis.
CASE SUMMARY A 72-year-old male with a body mass index of 20.9 was diagnosed with GHA with perigastric lymph node and liver metastasis. He underwent first-line chemotherapy but that failed. Pembrolizumab and bevacizumab with chemotherapy were used in the second-line treatment. The progression-free survival and overall survival were 14 mo and 16 mo, respectively, after treatment. In addition, the main adverse reaction was tolerable. The patient did not die of tumor progression.
CONCLUSION The combination of pembrolizumab and bevacizumab with chemotherapy is an effective and safe regimen for GHA and may be recommended as a new choice for GHA treatment. Further studies should evaluate this treatment in a larger cohort or a randomized controlled trial.
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Affiliation(s)
- Mei Liu
- Department of Medical Oncology, Haikou People's Hospital, Haikou 570100, Hainan Province, China
| | - Cheng Luo
- Department of Gynecology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya 572013, Hainan Province, China
| | - Zong-Zhou Xie
- Department of Medical Oncology, Haikou People's Hospital, Haikou 570100, Hainan Province, China
| | - Xun Li
- Department of Medical Oncology, Haikou People's Hospital, Haikou 570100, Hainan Province, China
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Weng W, Zhang M, Ni S, Tan C, Xu M, Wang X, Sun H, Wang L, Huang D, Sheng W. Decreased expression of claudin-18.2 in alpha-fetoprotein-producing gastric cancer compared to conventional gastric cancer. J Gastrointest Oncol 2022; 13:1035-1045. [PMID: 35837176 PMCID: PMC9274048 DOI: 10.21037/jgo-22-462] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 06/14/2022] [Indexed: 12/02/2024] Open
Abstract
BACKGROUND Alpha-fetoprotein-producing gastric cancer (AFPGC) is a subtype of gastric cancer (GC) with more aggressive biological behavior. As a highly specific tight junction component exclusively present in gastric mucosa and gastric adenocarcinomas, claudin-18.2 (CLDN18.2) has become an emerging target in GC. In this study, we aimed to provide insight into AFPGC and investigate the expression and the clinical implications of CLDN18.2 in AFPGC. METHODS We retrospectively collected 98 cases of AFPGC and reviewed their clinical, morphological, and immunohistochemical features. Another 356 patients with stage-matched conventional GC (cGC) were enrolled as a control group. We further surveyed CLDN18.2 expression by immunohistochemistry (IHC) in 51 AFPGC tissues and explained its association with the clinicopathological parameters of AFPGC. RESULTS Our results showed that AFPGC was a unique GC type with elevated serum alpha-fetoprotein (AFP), which was a predictor of a worse prognosis. AFPGC showed typical morphological features and positive staining of at least 1 hepatocytic or enteroblastic marker. The expression rate of CLDN18.2 was low, with a positivity rate of 21.6%, which was much lower than that observed in cGC tissues (38.5%). A significant correlation was found between CLDN18.2 expression and the differentiation of AFPGC. CLDN18.2 expression was negatively correlated with the serum AFP level of AFPGC. We also found that AFPGC with a hepatoid type (HPT) component showed a significantly lower CLDN18.2 expression than those without. CONCLUSIONS This study demonstrated that CLDN18.2 was significantly decreased in AFPGC and was negatively correlated with the patient's preoperative serum AFP level. The negative correlation between AFP and CLDN18.2 could be explained by retro-differentiation of AFPGC. Special treatment strategies might be needed for this unique tumor type.
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Affiliation(s)
- Weiwei Weng
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Meng Zhang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Shujuan Ni
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Cong Tan
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Midie Xu
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Xin Wang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Hui Sun
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Lei Wang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Dan Huang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
| | - Weiqi Sheng
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Pathology, Fudan University, Shanghai, China
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Chen Z, Ding C, Zhang T, He Y, Jiang G. Primary Hepatoid Adenocarcinoma of the Lung: A Systematic Literature Review. Onco Targets Ther 2022; 15:609-627. [PMID: 35676912 PMCID: PMC9167841 DOI: 10.2147/ott.s364465] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 05/16/2022] [Indexed: 12/15/2022] Open
Abstract
Background Hepatoid adenocarcinoma (HAC) of the lung (HAL) is a rare and aggressive extrahepatic adenocarcinoma with an unknown etiology and unfavorable prognosis, which is similar to the pathophysiological characteristics of hepatocellular carcinoma (HCC). Methods We first presented a 67-year-old patient diagnosed with HAC in the right middle lobe of the lung. Then, a systematic literature search was performed for HAL cases recorded between 1990 and 2020 based on three databases. The clinicopathological features, therapeutic method, and prognosis of this rare disease were reviewed, and corresponding prognostic factors were explored using Kaplan–Meier (K-M) curve and Cox proportional hazards regression model. Additionally, the potential biological mechanisms of HAL were further explored and compared with HCC and lung adenocarcinoma (LUAD) based on online databases. Results In the present study, we reported an HAL patient who underwent surgical resection combined with chemotherapy and succumbed to disease 13 months after surgery. Additionally, a total of 43 experimental studies with 49 HAL patients, including the present case, met the inclusion criteria and were included in the present review. We found that HAL is characterized by a male-dominated incidence and is more common in the right lung. Patients in the surgical subgroup have a better prognosis than those in the non-surgical subgroup (p = 0.034). Moreover, the Cox proportional hazards regression model demonstrated that surgical resection can significantly improve the prognosis of HAL patients (p = 0.016). HAL is a rare disease associated with gene mutations that has a distinctive cause and unique pathogenesis. Additionally, Afatinib and Gefitinib may be new effective agents to better combat HAL. Conclusion In conclusion, males may exhibit an increased risk of developing HAL and poorer prognosis than females. Surgical resection combined with chemotherapy may prolong the survival of patients with HAL. HAL has its unique clinicopathological characteristics and biological mechanisms.
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Affiliation(s)
- Zhitao Chen
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, People’s Republic of China
| | - Chenchen Ding
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, People’s Republic of China
| | - Ting Zhang
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, People’s Republic of China
| | - Yahui He
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, People’s Republic of China
- School of Medicine, Zhejiang Shuren University, Hangzhou, People’s Republic of China
| | - Guoping Jiang
- Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, People’s Republic of China
- Correspondence: Guoping Jiang, Department of Hepatobiliary Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, 848# Dongxin Road, Hangzhou City, Zhejiang Province, People’s Republic of China, Tel +86-0571-87236570, Email
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Kang M, Ma X, Shi J, Chen G, Jin X, Wang J, Lin L, Wu Z, Chen K, Xu J, Huang P, Chen J. Distinct molecular phenotype and the potential prognostic value of immune prognostic index and tumor infiltrating lymphocytes in hepatoid adenocarcinoma of stomach. Transl Oncol 2022; 19:101380. [PMID: 35276435 PMCID: PMC8908271 DOI: 10.1016/j.tranon.2022.101380] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 02/19/2022] [Indexed: 02/07/2023] Open
Abstract
Molecular classification of HAS should be mainly categorized into GS and CIN phenotypes with TP53 mutation. TILs and dNLR may help to screen appropriate candidates for ICIs treatment in HAS. dNLR demonstrated the potentiality as a reliable and economic predictor of prognosis in HAS. Hepatoid adenocarcinoma of the stomach (HAS) is a particular subtype of Gastric cancer (GC) with distinct pathological characteristics and genetic profile, but most HAS patients were received identical regimens as common GC. To date, only a few studies has been conducted to investigate the molecular characteristics of HAS, which may prevent the rational application of new anticancer strategies. To further obtain the genetic features and potential predictive and prognostic biomarkers of HAS, our current study evaluated the clinical implications of spectrum molecular markers in 36 surgical resection specimens. None Epstein-Barr virus (EBV) positive and/or micro-satellite instable high (MSI-h) tumors occurred in our study implies that the molecular classification of HAS should be mainly categorized into genomic stable (GS) and chromosomal instability (CIN) phenotypes, and wild type P53 status predicts better prognosis. More importantly, although the prognosis and clinical characteristics were independent of programmed cell death-ligand 1 (PD-L1), the presence of tumor infiltrating lymphocytes (TILs) still suggested that a portion of the enrolled HAS patients are potentially appropriate candidates for immune checkpoint blockade therapy. Additionally, the immune prognostic index (IPI) and derived neutrophil to lymphocyte ratio (dNLR) demonstrated their potential as reliable and economic indicators for predicting prognosis of HAS. We hope this first systematic evaluation will help in deciphering the molecular characterization and potential individualized regimens for this particular subtype of GC.
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Affiliation(s)
- Muxing Kang
- Department of Gastrointestinal Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, 310009, Hangzhou, Zhejiang 310000, China; Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China
| | - Xiaojing Ma
- Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China
| | - Jifei Shi
- Department of Gastrointestinal Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, 310009, Hangzhou, Zhejiang 310000, China; Department of General Surgery, The First Hospital of Pinghu, Jiaxing, Zhejiang 314200, China
| | - Guofeng Chen
- Department of Gastrointestinal Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, 310009, Hangzhou, Zhejiang 310000, China
| | - Xiaoli Jin
- Department of Gastrointestinal Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, 310009, Hangzhou, Zhejiang 310000, China
| | - Jun Wang
- Department of Gastrointestinal Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, 310009, Hangzhou, Zhejiang 310000, China
| | - Lele Lin
- Department of Gastrointestinal Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, 310009, Hangzhou, Zhejiang 310000, China
| | - Zhiwei Wu
- Department of Gastrointestinal Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, 310009, Hangzhou, Zhejiang 310000, China
| | - Kaibo Chen
- Department of Gastrointestinal Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, 310009, Hangzhou, Zhejiang 310000, China
| | - Jinghong Xu
- Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China
| | - Pintong Huang
- Department of Radiology, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, 310009, Hangzhou, Zhejiang 310000, China.
| | - Jian Chen
- Department of Gastrointestinal Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, 310009, Hangzhou, Zhejiang 310000, China.
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Case report: Hepatoid adenocarcinoma of soft tissue. CURRENT PROBLEMS IN CANCER: CASE REPORTS 2022. [DOI: 10.1016/j.cpccr.2021.100134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Zhou K, Wang A, Wei J, Ji K, Li Z, Ji X, Fu T, Jia Z, Wu X, Zhang J, Bu Z. The Value of Perioperative Chemotherapy for Patients With Hepatoid Adenocarcinoma of the Stomach Undergoing Radical Gastrectomy. Front Oncol 2022; 11:789104. [PMID: 35083146 PMCID: PMC8784750 DOI: 10.3389/fonc.2021.789104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 12/20/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Hepatoid adenocarcinoma of the stomach (HAS) is a rare type of gastric cancer, but the role of perioperative chemotherapy is still poorly understood. The aim of this retrospective study was to investigate the associations between perioperative chemotherapy and prognosis of HAS. METHOD We retrospectively analyzed patients with locally advanced HAS who received radical surgery in Peking University Cancer Hospital between November 2009 and October 2020. Patients were divided into neoadjuvant chemotherapy-first (NAC-first) group and surgery-first group. The relationships between perioperative chemotherapy and prognosis of HAS were analyzed using univariate, multivariate survival analyses and propensity score matching analysis (PSM). RESULTS A total of 100 patients were included for analysis, including 29 in the NAC-first group and 71 in the surgery-first group. The Her-2 amplification in HAS patients was 22.89% (19/83). For NAC-first group, 4 patients were diagnosed as tumor recession grade 1 (TRG1), 4 patients as TRG 2, and 19 patients as TRG 3. No significant difference in prognosis between the surgery-first group and the NAC-first group (P=0.108) was found using PSM analysis. In the surgery-first group, we found that the survival rate was better in group of ≥6 cycles of adjuvant chemotherapy than that of <6 cycles (P=0.013). CONCLUSION NAC based on platinum and fluorouracil may not improve the Overall survival (OS) and Disease-free survival time (DFS) of patients with locally advanced HAS. Patients who received ≥6 cycles of adjuvant chemotherapy had better survival. Therefore, the combination treatment of radical gastrectomy and sufficient adjuvant chemotherapy is recommended for patients with locally advanced HAS.
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Affiliation(s)
- Kai Zhou
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Anqiang Wang
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Jingtao Wei
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Ke Ji
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Zhongwu Li
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Xin Ji
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Tao Fu
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Ziyu Jia
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Xiaojiang Wu
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Ji Zhang
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
| | - Zhaode Bu
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
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Sukumaran R, Mathews A, Radhakrishnan N. Hepatic Metastasis from Hepatoid Adenocarcinoma of the Stomach Mimicking Hepatocellular Carcinoma: Diagnostic Challenge. CLINICAL CANCER INVESTIGATION JOURNAL 2022. [DOI: 10.51847/eddehtlu0r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Huang WP, Li LM, Li J, Yuan JH, Hou P, Liu CC, Ma YH, Liu XN, Han YJ, Liang P, Gao JB. Computed Tomography Features and Clinical Prognostic Characteristics of Hepatoid Adenocarcinoma of the Stomach. Front Oncol 2021; 11:772636. [PMID: 34956891 PMCID: PMC8696206 DOI: 10.3389/fonc.2021.772636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 11/22/2021] [Indexed: 11/13/2022] Open
Abstract
PURPOSE Hepatoid adenocarcinoma of the stomach (HAS) is a highly malignant and aggressive tumor. The purpose of this study was to describe the clinical, computed tomography (CT), and prognostic features of HAS to increase the awareness of this entity and determine its distinguishing features from non-HAS tumors. METHODS The CT features and clinical data of 47 patients in our hospital with pathologically documented HAS were retrospectively analyzed, and the relevant differences between pure HAS (pHAS) and mixed HAS (mHAS) were determined. In addition, 141 patients with non-HAS tumors in the same T stage in the same period were selected as the control group. The data were compared between the two groups, and factors affecting the prognosis of HAS were analyzed. In addition, we included 9 patients with HAS and 27 patients with non-HAS tumors from another center for external validation. RESULTS The patients in the HAS group were predominantly men (n = 33), and the tumor location was mostly the cardia or fundus (n = 27). Between the HAS and non-HAS groups, there were observed differences in terms of: sex, serum alpha-fetoprotein (AFP), carbohydrate antigen (CA)-125, and CA-724 levels; longest tumor diameter; degree of differentiation; vascular invasion; N stage, M stage, and tumor-node-metastasis (TNM) stage; thickest tumor diameter; plain CT attenuation; arterial-phase CT attenuation; CT attenuation between the venous and arterial phases; enhancement modes; and degrees of enhancement (all P < 0.05). In the data from another center for external validation, there were observed differences in terms of: age, degree of differentiation, vascular invasion, thickest tumor diameter, the ratio of arterial CT attenuation to CT attenuation of the abdominal aorta at the same level (RA), CT attenuation difference between the venous phase and arterial phase (HUv-a) (all P < 0.05). The results of the multivariate analysis revealed that the independent factors for differentiation were serum AFP level (P = 0.001), M stage (P = 0.038), and tumor enhancement on CT (P = 0.014). Among patients in the HAS group, 72.34% had pHAS and 27.66% had mHAS. The thickest tumor diameter and the longest short diameter of the metastatic lymph nodes of the mHAS group were on average 6.39 cm and 1.45 cm, respectively, which were larger than those in the pHAS group. The median progression-free survival time was 18.25 months in the HAS group, which was shorter than that in the non-HAS group (72.96 months; P = 0.001). The median overall survival time in the HAS group was 24.80 months, which was shorter than that in the non-HAS group (67.96 months; P = 0.001). The factors affecting the prognosis of HAS were M stage (P = 0.001), overall TNM stage (P = 0.048), presence of vascular cancer emboli (P = 0.040), and pHAS type (P = 0.046). Multifactorial analysis revealed that M stage (P = 0.027) and pHAS type (P = 0.009) were independent risk factors affecting the prognosis of HAS. CONCLUSION Although HAS is a rare clinical entity, it should be considered in the differential diagnosis of gastric tumors. Patients with HAS often have advanced-stage disease at presentation and a worse prognosis than patients with non-HAS tumors. CT findings, combined with laboratory results, can support the diagnosis of HAS. However, the final diagnosis needs to be confirmed with a histopathologic examination. If the postoperative pathologic findings reveal the mHAS type, a rapid clinical intervention and a detailed follow-up with CT are essential.
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Affiliation(s)
- Wen-peng Huang
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Li-ming Li
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jing Li
- Department of Radiology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, China
| | - Jun-hui Yuan
- Department of Radiology, The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, China
| | - Ping Hou
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Chen-chen Liu
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yi-hui Ma
- Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiao-nan Liu
- Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yi-jing Han
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Pan Liang
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jian-bo Gao
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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de Castria TB, Tang L, Queiroz MM, Awni BM, Paroder V, Shamseddine A, Bariani GM, Mukherji D, Matar CF, Fernandes GDS, El-Olayan A, Sabatin F, Elias R, Gupta R, Janjigian YY, Abou-Alfa GK. Hepatoid esophagogastric adenocarcinoma and tumoral heterogeneity: a case report. J Gastrointest Oncol 2021; 12:3123-3132. [PMID: 35070435 PMCID: PMC8748022 DOI: 10.21037/jgo-21-287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 09/30/2021] [Indexed: 08/30/2023] Open
Abstract
Hepatoid adenocarcinoma of the stomach is an uncommon subtype of gastric cancer remarkably similar to hepatocellular carcinoma in histopathological analysis. It is also commonly associated with high serum alfa-fetoprotein and a poorer prognosis, despite the emergence of new therapeutic options. In recent years, next generation sequencing (NGS) technology has made it possible to identify and describe the genes and molecular alterations common to gastric cancer thereby contributing to the advancement of targeted therapies. A 62-year-old patient, with no prior risk factor for hepatocellular carcinoma (HCC), presented to the emergency room with dysphagia for solids, abdominal pain and weight loss of about 3 kilograms over 3 months. Histopathological analysis presented with disparities regarding HER2 and programmed death-ligand 1 (PD-L1) status in the primary and metastatic sites. We describe a case of a de novo metastatic, human epidermal growth factor receptor 2 (HER2) positive esophagogastric junction hepatoid adenocarcinoma. Although this is a rare subgroup of gastric cancer, treatment strategies were based in recent studies in immunotherapy and guided therapy, taking into consideration the molecular findings from the patient's tumor NGS analysis. Data about HER2 and PDL1 heterogeneity were also reviewed. Despite the aggressiveness and rarity of this histology, the patient had a good response to treatment.
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Affiliation(s)
- Tiago Biachi de Castria
- Centro de Oncologia, Hospital Sírio-Libanês, São Paulo, SP, Brasil
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Laura Tang
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Medical College at Cornell University, New York, NY, USA
| | | | | | - Viktoriya Paroder
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Medical College at Cornell University, New York, NY, USA
| | | | | | | | | | | | - Ashwaq El-Olayan
- National Guard Hospital, King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia
| | - Fouad Sabatin
- National Guard Hospital, King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia
| | | | | | - Yelena Y. Janjigian
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Medical College at Cornell University, New York, NY, USA
| | - Ghassan K. Abou-Alfa
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Weill Medical College at Cornell University, New York, NY, USA
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Sun H, Li X, Zhang J, Liu Y. Clinicopathological features and genomic profiles of hepatoid adenocarcinoma of the lung: Report of four cases. Pathol Res Pract 2021; 229:153652. [PMID: 34826742 DOI: 10.1016/j.prp.2021.153652] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 10/05/2021] [Accepted: 10/06/2021] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Pathological features of hepatoid adenocarcinoma of the lung (HAL) are similar to those of hepatocellular carcinoma (HCC) and HAL has a poor prognosis. In this study, we aimed to elucidate clinicopathologic and molecular features of HAL. METHODS Four cases of HAL patients with one lobe of the lung resected were enrolled into the study. Next generation sequencing (NGS) of a 425-gene panel was performed on tumor tissue samples. RESULTS The most frequently mutated gene was TP53 in three cases of primary HAL and one case of metastatic HAL, with a mutation rate of 100%. Also, CDK8, CDKN2A, EPHA5, SMARCA4, and STK11 were detected as high-frequency mutations, with a mutation rate of 50%. The types of TP53 mutation included two missense variants and two frameshift ones. The TP53 mutation was related to the occurrence of HAL. CONCLUSION HAL could be caused by genetic mutations and is closely related to TP53 mutation.
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Affiliation(s)
- Hui Sun
- Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, PR China
| | - Xiaoli Li
- Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, PR China
| | - Jianguo Zhang
- Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, PR China.
| | - Yifei Liu
- Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, PR China.
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Li X, Chen S, Zhu Y, Fei J, Song L, Sun G, Niu W, Guo L, Wang J. Comprehensive bioinformatics analyses identified Homeobox B9 as a potential prognostic biomarker and therapeutic target for gastric cancer. J Gastrointest Oncol 2021; 12:2132-2149. [PMID: 34790380 DOI: 10.21037/jgo-21-598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 10/16/2021] [Indexed: 12/24/2022] Open
Abstract
Background The Homeobox B (HOXB) family promotes tumor progression, but the mechanism of its action in gastric cancer (GC) is unclear. We sought to identify the HOXB family members that are critical to the prognosis of GC patients. Methods The Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), cBioPortal, UALCAN, Kaplan-Meier plotter, and the GeneMANIA databases were used to analyze the messenger RNA (mRNA) expression levels, prognostic value, and gene-gene interaction network of the HOXB9 family members in GC. The expression of HOXB9 in GC and its relationship with various clinicopathological parameters and the prognosis of patients were verified by immunohistochemistry. Results The expression of HOXB3, HOXB5, HOXB6, HOXB7, HOXB9, and HOXB13 mRNA was significantly upregulated in GC. There was a significant correlation between the upregulation of HOXB3, HOXB5, and HOXB9 mRNA and a low overall survival (OS) rate. The high expression of HOXB7, HOXB9, and HOXB13 mRNA was closely correlated to tumor grade and stage. HOXB9 was the HOXB family member most closely related to the occurrence and development of GC. A further analysis showed that HOXB9 might be involved in deoxyribonucleic acid repair and division regulation. A validation study showed that the advanced cancer group had a higher level of HOXB9 expression than the early cancer group. The high expression of HOXB9 in gastric tissue plays an important role in the survival and prognosis of GC patients. Conclusions HOXB family members have different degrees of abnormal expression in GC. High HOXB9 expression in GC tissues was significantly correlated with a worse prognosis. Thus, HOXB9 is a potential novel biomarker and therapeutic target for GC.
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Affiliation(s)
- Xiaofei Li
- Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Shujia Chen
- Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Yinghui Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Jiayue Fei
- Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Liaoyuan Song
- Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Guoyan Sun
- Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Wei Niu
- Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Lianyi Guo
- Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Jiwei Wang
- Department of Gastrointestinal Surgery, Xuzhou Central Hospital, Xuzhou, China
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Wei L, Chen J, Song C, Zhang Y, Zhang Y, Xu M, Feng C, Gao Y, Qian F, Wang Q, Shang D, Zhou X, Zhu J, Wang X, Jia Y, Liu J, Zhu Y, Li C. Cancer CRC: A Comprehensive Cancer Core Transcriptional Regulatory Circuit Resource and Analysis Platform. Front Oncol 2021; 11:761700. [PMID: 34712617 PMCID: PMC8546348 DOI: 10.3389/fonc.2021.761700] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 09/24/2021] [Indexed: 11/30/2022] Open
Abstract
A core transcriptional regulatory circuit (CRC) is a group of interconnected auto-regulating transcription factors (TFs) that form loops and can be identified by super-enhancers (SEs). Studies have indicated that CRCs play an important role in defining cellular identity and determining cellular fate. Additionally, core TFs in CRCs are regulators of cell-type-specific transcriptional regulation. However, a global view of CRC properties across various cancer types has not been generated. Thus, we integrated paired cancer ATAC-seq and H3K27ac ChIP-seq data for specific cell lines to develop the Cancer CRC (http://bio.liclab.net/Cancer_crc/index.html). This platform documented 94,108 cancer CRCs, including 325 core TFs. The cancer CRC also provided the “SE active core TFs analysis” and “TF enrichment analysis” tools to identify potentially key TFs in cancer. In addition, we performed a comprehensive analysis of core TFs in various cancer types to reveal conserved and cancer-specific TFs.
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Affiliation(s)
- Ling Wei
- School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, China.,The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, China.,Cardiovascular Lab of Big Data and Imaging Artificial Intelligence, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Jiaxin Chen
- School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, China
| | - Chao Song
- School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, China.,The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, China.,Cardiovascular Lab of Big Data and Imaging Artificial Intelligence, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Yuexin Zhang
- School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, China
| | - Yimeng Zhang
- School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, China
| | - Mingcong Xu
- School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, China
| | - Chenchen Feng
- School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, China
| | - Yu Gao
- School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, China
| | - Fengcui Qian
- School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, China.,The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, China.,Cardiovascular Lab of Big Data and Imaging Artificial Intelligence, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Qiuyu Wang
- School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, China.,The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, China.,Cardiovascular Lab of Big Data and Imaging Artificial Intelligence, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.,School of Computer, University of South China, Hengyang, China.,Hunan Provincial Base for Scientific and Technological Innovation Cooperation, University of South China, Hengyang, China
| | - Desi Shang
- The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, China.,Cardiovascular Lab of Big Data and Imaging Artificial Intelligence, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.,School of Computer, University of South China, Hengyang, China.,Hunan Provincial Base for Scientific and Technological Innovation Cooperation, University of South China, Hengyang, China
| | - Xinyuan Zhou
- School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, China
| | - Jiang Zhu
- School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, China
| | - Xiaopeng Wang
- School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, China
| | - Yijie Jia
- School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, China
| | - Jiaqi Liu
- The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, China.,Cardiovascular Lab of Big Data and Imaging Artificial Intelligence, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.,School of Computer, University of South China, Hengyang, China.,Hunan Provincial Base for Scientific and Technological Innovation Cooperation, University of South China, Hengyang, China
| | - Yanbing Zhu
- Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Beijing Clinical Research Institute, Beijing, China
| | - Chunquan Li
- The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, China.,School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, China.,Cardiovascular Lab of Big Data and Imaging Artificial Intelligence, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.,School of Computer, University of South China, Hengyang, China.,Hunan Provincial Base for Scientific and Technological Innovation Cooperation, University of South China, Hengyang, China.,General Surgery Department, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin, China
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Lin JX, Wang ZK, Hong QQ, Zhang P, Zhang ZZ, He L, Wang Q, Shang L, Wang LJ, Sun YF, Li ZX, Liu JJ, Ding FH, Lin ED, Fu YA, Lin SM, Xie JW, Li P, Zheng CH, Huang CM. Assessment of Clinicopathological Characteristics and Development of an Individualized Prognostic Model for Patients With Hepatoid Adenocarcinoma of the Stomach. JAMA Netw Open 2021; 4:e2128217. [PMID: 34609494 PMCID: PMC8493440 DOI: 10.1001/jamanetworkopen.2021.28217] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
IMPORTANCE Few studies have examined the clinicopathological characteristics and prognoses of patients with hepatoid adenocarcinoma of the stomach (HAS). OBJECTIVE To explore the clinicopathological characteristics and prognoses of patients with HAS and develop a nomogram to predict overall survival (OS). DESIGN, SETTING, AND PARTICIPANTS This prognostic study involved a retrospective analysis of data from 315 patients who received a diagnosis of primary HAS between April 1, 2004, and December 31, 2019, at 14 centers in China. MAIN OUTCOMES AND MEASURES OS and prognostic factors. Patients were randomly assigned to a derivation cohort (n = 220) and a validation cohort (n = 95). A nomogram was developed based on independent prognostic factors identified through a multivariable Cox mixed-effects model. RESULTS Among 315 patients with HAS (mean [SD] age, 61.9 [10.2] years; 240 men [76.2%]), 137 patients had simple HAS (defined as the presence of histologically contained hepatoid differentiation areas only), and 178 patients had mixed HAS (defined as the presence of hepatoid differentiation areas plus common adenocarcinoma areas). Patients with simple HAS had a higher median preoperative α-fetoprotein level than those with mixed HAS (195.9 ng/mL vs 48.9 ng/mL, respectively; P < .001) and a higher rate of preoperative liver metastasis (23 of 137 patients [16.8%] vs 11 of 178 patients [6.2%]; P = .003). The 3-year OS rates of patients with simple vs mixed HAS were comparable (56.0% vs 60.0%; log-rank P = .98). A multivariable Cox analysis of the derivation cohort found that the presence of perineural invasion (hazard ratio [HR], 2.13; 95% CI, 1.27-3.55; P = .009), preoperative carcinoembryonic antigen levels of 5 ng/mL or greater (HR, 1.72; 95% CI, 1.08-2.74; P = .03), and pathological node category 3b (HR, 3.72; 95% CI, 1.34-10.32; P = .01) were independent risk factors for worse OS. Based on these factors, a nomogram to predict postoperative OS was developed. The concordance indices of the nomogram (derivation cohort: 0.72 [95% CI, 0.66-0.78]; validation cohort: 0.72 [95% CI, 0.63-0.81]; whole cohort: 0.71 [95% CI, 0.66-0.76]) were higher than those derived using the American Joint Committee on Cancer's AJCC Cancer Staging Manual (8th edition) pathological tumor-node-metastasis (pTNM) staging system (derivation cohort: 0.63 [95% CI, 0.57-0.69]; validation cohort: 0.65 [95% CI, 0.56-0.75]; whole cohort: 0.64 [95% CI, 0.59-0.69]) and those derived using a clinical model that included pTNM stage and receipt of adjuvant chemotherapy (derivation cohort: 0.64 [95% CI, 0.58-0.69]; validation cohort: 0.65 [95% CI, 0.56-0.75]; whole cohort: 0.64 [95% CI, 0.59-0.69]). Based on the nomogram cutoff of 10 points, the whole cohort was divided into high-risk and low-risk groups. The 3-year OS rate of patients in the high-risk group was significantly lower than that of patients in the low-risk group (29.7% vs 75.9%, respectively; log-rank P < .001), and the 3-year prognosis of high-risk and low-risk groups could be further distinguished into pTNM stage I to II (33.3% vs 80.2%; exact log-rank P = .15), stage III (34.3% vs 71.3%; log-rank P < .001), and stage IV (15.5% vs 70.3%; log-rank P = .009). CONCLUSIONS AND RELEVANCE This study found that perineural invasion, preoperative carcinoembryonic antigen levels of 5 ng/mL or greater, and pathological node category 3b were independent risk factors associated with worse OS. An individualized nomogram was developed to predict OS among patients with HAS. This nomogram had good prognostic value and may be useful as a supplement to the current American Joint Committee on Cancer TNM staging system.
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Affiliation(s)
- Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Zu-Kai Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Qing-Qi Hong
- Department of Gastrointestinal Oncology Surgery, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Peng Zhang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zi-Zhen Zhang
- Department of Gastrointestinal Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Liang He
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, China
| | - Quan Wang
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, China
| | - Liang Shang
- Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Lin-Jun Wang
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ya-Feng Sun
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Zhi-Xiong Li
- Gastrointestinal Surgery Unit 1, Teaching Hospital of Putian First Hospital of Fujian Medical University, Putian, China
| | - Jun-Jie Liu
- Gastrointestinal Department of The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Fang-Hui Ding
- General Surgery Department, The First Hospital of Lanzhou University, Lanzhou, China
| | - En-De Lin
- Department of General Surgery, Zhongshan Hospital Affiliated with Xiamen University, Xiamen, China
| | - Yong-An Fu
- Department of Gastrointestinal Surgery, Affiliated Quanzhou First Hospital to Fujian Medical University, Quanzhou, China
| | - Shuang-Ming Lin
- Department of Gastrointestinal Surgery, Longyan First Hospital Affiliated with Fujian Medical University, Longyan, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
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Lawlor RT, Mafficini A, Sciammarella C, Cantù C, Rusev BC, Piredda ML, Antonello D, Grimaldi S, Bonizzato G, Sperandio N, Marchegiani G, Malleo G, Pea A, Salvia R, Mombello A, Mazzoleni G, Nottegar A, Hanspeter E, Riva G, Tomezzoli A, Bencivenga M, de Manzoni G, Pedron S, Paolino G, Mattiolo P, Brosens LA, Silvestris N, Fassan M, Cooke SL, Beer PA, Milella M, Adsay VN, Cheng L, Scarpa A, Luchini C. Genomic characterization of hepatoid tumors: context matters. Hum Pathol 2021; 118:30-41. [PMID: 34562502 DOI: 10.1016/j.humpath.2021.09.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 09/10/2021] [Indexed: 12/30/2022]
Abstract
Hepatoid tumors (HT) are rare neoplasms morphologically resembling hepatocellular carcinoma, which arise in several organs other than the liver. A comprehensive molecular profile of this group of neoplasms is still lacking. Genomic characterization of 19 HTs from different organs (three colon HTs, four esophagogastric HTs, four biliary HTs, six genitourinary HTs, two lung HTs) was performed using a multigene next-generation sequencing panel. NGS unraveled a composite molecular profile of HT. Their genetic alterations were clearly clustered by tumor site: (i) colorectal HT displayed microsatellite instability, high tumor mutational burden, mutations in ARID1A/B genes and NCOA4-RET gene fusion (2/3 cases); (ii) gastric HT had TP53 mutations (2/4); (iii) biliary HT displayed loss of CDKN2A (3/4) and loss of chromosome 18 (2/4); (iv) genital HT showed gain of chromosome 12 (3/6); (v) lung HT had STK11 somatic mutations (2/2). The only commonly mutated gene occurring in HT of different sites was TP53 (8/19 cases: colon 2, esophagogastric 2, biliary 2, genital 1, lungs 1). This study shows that most genetic alterations of HT were clustered by site, indicating that context matters. The novel potential targets for HT precision oncology are also clustered based on the anatomic origin. This study shed light on the biology of these rare cancers and may have important consequences for treatment decisions and clinical trial selection for HT patients.
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Affiliation(s)
- Rita T Lawlor
- ARC-Net Research Center for Applied Research on Cancer, University of Verona, 37134 Verona, Italy
| | - Andrea Mafficini
- ARC-Net Research Center for Applied Research on Cancer, University of Verona, 37134 Verona, Italy; Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Concetta Sciammarella
- ARC-Net Research Center for Applied Research on Cancer, University of Verona, 37134 Verona, Italy
| | - Cinzia Cantù
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Borislav C Rusev
- ARC-Net Research Center for Applied Research on Cancer, University of Verona, 37134 Verona, Italy
| | - Maria L Piredda
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Davide Antonello
- Department of Surgery, The Pancreas Institute, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Sonia Grimaldi
- ARC-Net Research Center for Applied Research on Cancer, University of Verona, 37134 Verona, Italy
| | - Giada Bonizzato
- ARC-Net Research Center for Applied Research on Cancer, University of Verona, 37134 Verona, Italy
| | - Nicola Sperandio
- ARC-Net Research Center for Applied Research on Cancer, University of Verona, 37134 Verona, Italy
| | - Giovanni Marchegiani
- Department of Surgery, The Pancreas Institute, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Giuseppe Malleo
- Department of Surgery, The Pancreas Institute, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Antonio Pea
- Department of Surgery, The Pancreas Institute, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Roberto Salvia
- Department of Surgery, The Pancreas Institute, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Aldo Mombello
- ARC-Net Research Center for Applied Research on Cancer, University of Verona, 37134 Verona, Italy
| | - Guido Mazzoleni
- Department of Pathology, Central Hospital of Bolzano, 39100 Bolzano, Italy
| | - Alessia Nottegar
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Esther Hanspeter
- Department of Pathology, Central Hospital of Bolzano, 39100 Bolzano, Italy
| | - Giulio Riva
- Department of Diagnostics, Pathology Unit, San Bortolo Hospital, 36100 Vicenza, Italy
| | - Anna Tomezzoli
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Maria Bencivenga
- Unit of General and Upper GI Surgery, University of Verona, 37134 Verona, Italy
| | - Giovanni de Manzoni
- Unit of General and Upper GI Surgery, University of Verona, 37134 Verona, Italy
| | - Serena Pedron
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Gaetano Paolino
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Paola Mattiolo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Lodewijk A Brosens
- Department of Pathology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands; Department of Pathology, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
| | - Nicola Silvestris
- IRCCS Istituto Tumori "Giovanni Paolo II" of Bari, and Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", 70121 Bari, Italy
| | - Matteo Fassan
- Department of Medicine (DIMED), University of Padua, 35121 Padua, Italy
| | - Susanna L Cooke
- Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Bearsden, G61 1QH Glasgow, UK
| | - Philip A Beer
- Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Bearsden, G61 1QH Glasgow, UK; Sanger Institute, Wellcome Trust Genome Campus, CB10 1SA Cambridge, UK
| | - Michele Milella
- Department of Medicine, Section of Oncology, University and Hospital Trust of Verona, 37134 Verona, Italy
| | - Volkan N Adsay
- Department of Pathology, Koç University Hospital and Koç University Research Center for Translational Medicine (KUTTAM), 34010 Istanbul, Turkey
| | - Liang Cheng
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 46202 Indianapolis, IN, USA
| | - Aldo Scarpa
- ARC-Net Research Center for Applied Research on Cancer, University of Verona, 37134 Verona, Italy; Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy.
| | - Claudio Luchini
- ARC-Net Research Center for Applied Research on Cancer, University of Verona, 37134 Verona, Italy; Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy.
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Ranceva A, Stulpinas R, Norvilas R, Mickys U. Hepatoid adenocarcinoma of the stomach with PIK3Ca mutation during pregnancy: A case report with molecular profile. Oxf Med Case Reports 2021; 2021:omab078. [PMID: 34527251 PMCID: PMC8436274 DOI: 10.1093/omcr/omab078] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 07/10/2021] [Accepted: 07/13/2021] [Indexed: 12/30/2022] Open
Abstract
Hepatoid adenocarcinoma is an extremely aggressive special subtype of gastric tumors. It can be lethal as no standard treatment options for this type of gastric cancer exist. Here, we describe a very rare case of a young female on her 21st week of pregnancy who was diagnosed with stage IV hepatoid adenocarcinoma of the stomach with elevated α fetoprotein (AFP) level. Gene mutation analysis performed by next-generation sequencing identified somatic mutations in the PIK3CA gene. Despite the treatment, patient died 2 months after the initial disease presentation. To our best knowledge, this case represents the first report of pregnancy-associated hepatoid gastric adenocarcinoma with the PIK3CA gene mutations, which can provide further clues for the understanding of molecular features of this type of tumor that can reflect biological behavior and may lead to further effective treatment options.
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Affiliation(s)
- Anastasija Ranceva
- Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
| | - Rokas Stulpinas
- National Center of Pathology, Affiliate of Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
| | - Rimvydas Norvilas
- Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
| | - Ugnius Mickys
- National Center of Pathology, Affiliate of Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
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Yang Y, Li Y, Du X. Prognostic Analysis of Gastric Signet Ring Cell Carcinoma and Hepatoid Adenocarcinoma of the Stomach: A Propensity Score-Matched Study. Front Oncol 2021; 11:716962. [PMID: 34458152 PMCID: PMC8385756 DOI: 10.3389/fonc.2021.716962] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Accepted: 07/26/2021] [Indexed: 12/19/2022] Open
Abstract
Background Hepatoid adenocarcinoma of the stomach (HAS) is a rare type of primary gastric cancer, and most previous studies have reported that HAS has a poor prognosis due to its aggressive biological behavior. The aim of this study was to compare the prognosis of HAS to that of gastric signet ring cell carcinoma (SRC). Methods This was a single-center, retrospective, observational cohort study (January 2010 to January 2016) of gastric cancer patients with pathological HAS and SRC. Overall survival was compared between HAS and SRC patients. We used univariate Cox regression, multivariate Cox regression, propensity score matching (PSM), inverse probability of treatment weighting, standardized mortality ratio weighting, standardized mortality ratio weighting, and overlap weighting to perform a prognostic analysis. Results A total of 725 (672 SRC and 53 HAS) patients were included. After nearest-neighbor 1:4 PSM, 200 SRC patients and 50 HAS patients were matched. Only in univariate Cox regression analysis with the cohort before PSM did HAS show a significantly worse prognosis than SRC [hazard ratio (HR), 1.66; 95% confidence interval (CI), 1.02-2.69, p = 0.040]. However, in the analysis of multivariate Cox regression with the cohort before PSM and series analysis based on the propensity score, all of the results indicated that there was no statistically significant difference in overall survival between HAS and SRC (all p > 0.05). Furthermore, in the subgroup of proximal location (p = 0.027), T stage 4a & 4b (p = 0.001), N stage 3a & 3b (p = 0.022), with cancer nodules (p = 0.026), serum CEA higher than the normal value (p = 0.038), and serum CA199 higher than the normal value (p = 0.023), the prognosis of HAS was significantly worse than that of SRC. Conclusion Based on our study, there was no statistically significant difference in overall survival between HAS and gastric SRC patients. However, in patients with an advanced tumor stage, HAS may have a worse overall survival than SRC.
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Affiliation(s)
- Yu Yang
- Department of General Surgery, First Medical Center of Chinese People's Liberation Army (PLA), General Hospital, Beijing, China
| | - Yuxuan Li
- Department of General Surgery, First Medical Center of Chinese People's Liberation Army (PLA), General Hospital, Beijing, China
| | - Xiaohui Du
- Department of General Surgery, First Medical Center of Chinese People's Liberation Army (PLA), General Hospital, Beijing, China
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Li Z, Zhou Q, Lu J, Zhang H, Teng L. Carcinosarcoma of the stomach with alpha-fetoprotein-producing hepatoid adenocarcinoma: an unexpected combination of two rare subtypes of gastric cancer in one tumor. J Int Med Res 2021; 49:3000605211037422. [PMID: 34407682 PMCID: PMC8381432 DOI: 10.1177/03000605211037422] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Carcinosarcoma is a rare malignant neoplasm comprising both epithelial and
mesenchymal components. Hepatoid adenocarcinoma (HAC) is another rare type of
cancer. To date, there are only four reported cases of concurrent
carcinosarcomas with HAC across all tumor types, all of which were observed in
uterine tumors. Here, we report an unusual case of gastric carcinosarcoma
associated with alpha-fetoprotein (AFP)-producing HAC in a 76-year-old woman.
Upon admission, the patient had an elevated serum AFP concentration (448 µg/L),
a necrotic polypoid tumor of the central gastric cardia revealed by endoscopy,
and no evidence of distant metastasis indicated by computed tomography (CT).
Owing to malignancy indicated by biopsy, the patient underwent proximal subtotal
gastrectomy. The resected tumor was composed of both an HAC component and a
sarcoma component, microscopically. The sample was positive for AFP, hepatocyte
paraffin (Hep-Par) 1, glypican-3, SALL4, CDX2, cytokeratin (CK) (pan), CK18,
desmin, and vimentin staining immunohistochemically. In summary, the tumor was
diagnosed as carcinosarcoma of the stomach with AFP-producing HAC. To our
knowledge, this is the first report of gastric carcinosarcoma with AFP-producing
HAC in the English literature describing gastric tumors.
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Affiliation(s)
- Zhongqi Li
- Department of Surgical Oncology, 26441Zhejiang University School of Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Quan Zhou
- Department of Surgical Oncology, 26441Zhejiang University School of Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jun Lu
- Department of Surgical Oncology, 26441Zhejiang University School of Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Haibin Zhang
- Department of Surgical Oncology, 26441Zhejiang University School of Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lisong Teng
- Department of Surgical Oncology, 26441Zhejiang University School of Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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