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Zhang S, Lin Y, Li Z, Wang Z, Luo R, Zhang X. Clinical treatment strategy and follow-up of lymphoepithelioma-like carcinoma: a retrospective study. Future Sci OA 2024; 10:2384878. [PMID: 39215389 PMCID: PMC11385158 DOI: 10.1080/20565623.2024.2384878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 07/22/2024] [Indexed: 09/04/2024] Open
Abstract
Aim: To investigate the clinical features, diagnosis and treatment of lymphoepithelioma-like carcinoma (LELC).Materials & methods: The clinical data of 114 LELC patients were retrospectively analyzed.Results: Ninety-eight patients (86.0%) were Epstein-Barr virus-encoded small RNA (EBER) positive detected by situ hybridization. A 67.1% (51/76) patients had PD-L1 expression. The 5-year overall survival rate of EBER negative patients was 51.6% while the rate of positive patients was 84.8% (p = 0.015). The 5-year progression free survival rate of EBER negative patients was 40.2% while the rate of positive patients was 70.2% (p = 0.004).Conclusion: The progression of LELC is relatively slow and present a better prognosis. The occurrence of tumor is closely related to Epstein-Barr virus infection and PD-L1 is highly expressed in tumor cells.
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Affiliation(s)
- Shilong Zhang
- Department of Medical Oncology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yufu Lin
- Department of Medical Oncology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
- Xiamen Clinical Research Center for Cancer Therapy, Xiamen, China
- Clinical Research Center for Precision Medicine of Abdominal Tumor of Fujian Province, Xiamen, China
| | - Zhiyong Li
- Department of Medical Oncology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
- Xiamen Clinical Research Center for Cancer Therapy, Xiamen, China
- Clinical Research Center for Precision Medicine of Abdominal Tumor of Fujian Province, Xiamen, China
| | - Zhiming Wang
- Department of Medical Oncology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Rongkui Luo
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiuping Zhang
- Department of Medical Oncology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
- Xiamen Clinical Research Center for Cancer Therapy, Xiamen, China
- Clinical Research Center for Precision Medicine of Abdominal Tumor of Fujian Province, Xiamen, China
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Zheng L, Zhou N, Yang X, Wei Y, Yi C, Gou H. Clinicopathological features of a rare cancer: Intrahepatic lymphoepithelioma-like cholangiocarcinoma with Epstein-Barr virus infection. Clin Res Hepatol Gastroenterol 2023; 47:102244. [PMID: 37944749 DOI: 10.1016/j.clinre.2023.102244] [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: 09/06/2023] [Revised: 10/15/2023] [Accepted: 11/06/2023] [Indexed: 11/12/2023]
Abstract
PURPOSE Epstein-Barr virus-related lymphoepithelioma-like cholangiocarcinoma (EBV-LELCC), a subtype of intrahepatic cholangiocarcinoma (IHCC), is an extremely rare cancer. To date, only few cases have been reported. Therefore, more studies are needed to provide new insights into its clinicopathological characteristics and treatment. METHODS We retrospectively collected data from 16 EBV-LELCC patients admitted to our hospital between January 2013 and February 2022. We summarized their clinical characteristics and analyzed the genomic features of 5 patients by whole-exon sequencing. In addition, the Kaplan-Meier method was used to assess the prognostic differences between EBV-LELCC and EBV-negative IHCC. RESULTS A total of 16 EBV-LELCC patients aged between 35 and 70 were included in this study and were characterized by female predominance. Eight genetic mutations including KMT2C, ARID1B, BAZ1A, NPM1, POLE, PER3, TOPBP1, USP1 were identified from 5 patients. There were 11 stage I, 2 stage III and 3 stage IV patients in this study. The overall survival of stage I and stage III EBV-LELCC patients after radical surgery was significantly better than that of EBV-negative IHCC patients with matched stage (p = 0.0119). Notably, a stage IV patient treated with a variety of antitumor modalities including surgery, interventional therapy, radiotherapy, chemotherapy, targeted therapy and immunotherapy achieved long-term survival of more than seven years. CONCLUSION Altogether, EBV-LELCC presents a more favorable prognosis than IHCC. This study suggests that patients with early EBV-LELCC have a good prognosis after radical surgery, and even patients with advanced EBV-LELCC are expected to have a longer survival under appropriate and timely treatment. For such a rare cancer with unique clinicopathological features and molecular patterns, more research is needed to facilitate its diagnosis and treatment.
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Affiliation(s)
- Lingnan Zheng
- Abdominal Oncology Ward, Division of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Nan Zhou
- Gastric Cancer Center, Division of Medical Oncology, Cancer Center, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Xi Yang
- Division of Radiotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Yuanfeng Wei
- Abdominal Oncology Ward, Division of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Cheng Yi
- Abdominal Oncology Ward, Division of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Hongfeng Gou
- Gastric Cancer Center, Division of Medical Oncology, Cancer Center, Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
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Lei Y, Cao P, Zheng X, Wei J, Cheng M, Liu M. Perspectives for immunotherapy of EBV-associated GLELC: A relatively "hot" tumor microenvironment. Cancer Med 2023; 12:19838-19849. [PMID: 37732493 PMCID: PMC10587976 DOI: 10.1002/cam4.6555] [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: 07/21/2022] [Revised: 09/01/2023] [Accepted: 09/08/2023] [Indexed: 09/22/2023] Open
Abstract
BACKGROUND Epstein-Barr virus (EBV)-associated gastric lymphoepithelioma-like carcinoma (EBVaGLELC) represents a small number of gastric cancer (GC), and research on tumor microenvironment (TME) and treatment strategy are still lacking. AIMS Here, we aim to elucidate the immune features of this rare disease and further help to develop more effective treatment options. MATERIALS & METHODS A retrospective analysis was conducted between 2019 to 2022 in West China Hospital to reveal the immunological characteristics of EBV-positive GLELC. The difference of immune cell subset and tumor vascular structure between gastric denocarcinoma (GAC) and EBVaGLELC will be pointed out. DISCUSSION 13 patients with GELEC and 8 patients with GAC were retrospectively studied. The heterogeneity of the immune cell profile was then confirmed through multiplexed immunofluorescence staining (mIF), which revealed a higher proportion of CD3+ T cells, CD8+ T cells, and Treg cells in the EBV-associated GLELC group. Such a distinct TME may provide therapeutic advantages, and patients with this rare subtype of GC could be good candidates for immune checkpoint inhibitors (ICIs). Angiogenesis in EBV-positive GLELC may be less intense than that in gastric adenocarcinoma (GAC), a feature that might decrease their susceptibility to antiangiogenic therapy. Furthermore, we reported a 52-year-old male with advanced EBV-positive GLELC who showed a favorable response to the combined therapy with . A repeat evaluation showed sustained partial response (PR), and the progression-free survival (PFS) was more than 34 months until now. CONCLUSION Compared with GAC, EBVaGLELC revealed higher T cell infiltration and less intense of angiogenesis. It displays relatively "hot" TME that may provide the rationality to treat with immunotherapy in EBV-related GLELC.
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Affiliation(s)
- Yanna Lei
- Department of Gastric Cancer Center, West China HospitalSichuan UniversityChengduSichuanChina
- Department of Abdominal Oncology, West China HospitalSichuan UniversityChengduSichuanChina
| | - Peng Cao
- Department of Abdominal Oncology, West China HospitalSichuan UniversityChengduSichuanChina
- Department of Colorectal Cancer Center, West China HospitalSichuan UniversityChengduSichuanChina
| | - Xiufeng Zheng
- Department of Gastric Cancer Center, West China HospitalSichuan UniversityChengduSichuanChina
- Department of Abdominal Oncology, West China HospitalSichuan UniversityChengduSichuanChina
| | - Jing Wei
- Department of Gastric Cancer Center, West China HospitalSichuan UniversityChengduSichuanChina
- Department of Abdominal Oncology, West China HospitalSichuan UniversityChengduSichuanChina
| | - Mo Cheng
- Department of Gastric Cancer Center, West China HospitalSichuan UniversityChengduSichuanChina
- Department of Abdominal Oncology, West China HospitalSichuan UniversityChengduSichuanChina
| | - Ming Liu
- Department of Gastric Cancer Center, West China HospitalSichuan UniversityChengduSichuanChina
- Department of Abdominal Oncology, West China HospitalSichuan UniversityChengduSichuanChina
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Knerr JM, Kledal TN, Rosenkilde MM. Molecular Properties and Therapeutic Targeting of the EBV-Encoded Receptor BILF1. Cancers (Basel) 2021; 13:4079. [PMID: 34439235 PMCID: PMC8392491 DOI: 10.3390/cancers13164079] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 08/05/2021] [Accepted: 08/09/2021] [Indexed: 12/12/2022] Open
Abstract
The γ-herpesvirus Epstein-Barr Virus (EBV) establishes lifelong infections in approximately 90% of adults worldwide. Up to 1,000,000 people yearly are estimated to suffer from health conditions attributed to the infection with this virus, such as nasopharyngeal and gastric carcinomas as well as several forms of B, T and NK cell lymphoma. To date, no EBV-specific therapeutic option has reached the market, greatly reducing the survival prognoses of affected patients. Similar to other herpesviruses, EBV encodes for a G protein-coupled receptor (GPCR), BILF1, affecting a multitude of cellular signaling pathways. BILF1 has been identified to promote immune evasion and tumorigenesis, effectively ensuring a life-long persistence of EBV in, and driving detrimental health conditions to its host. This review summarizes the epidemiology of EBV-associated malignancies, their current standard-of-care, EBV-specific therapeutics in development, GPCRs and their druggability, and most importantly consolidates the findings of over 15 years of research on BILF1 in the context of EBV-specific drug development. Taken together, BILF1 constitutes a promising target for the development of novel EBV-specific therapeutics.
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Affiliation(s)
- Julius Maximilian Knerr
- Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, University of Copenhagen, 2200 København, Denmark;
| | | | - Mette Marie Rosenkilde
- Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, University of Copenhagen, 2200 København, Denmark;
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5
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Abstract
Pulmonary lymphoepithelioma-like carcinoma is a rare type of non-small cell lung cancer. The tumor is usually discovered in young, nonsmoking Asian populations. The patients are diagnosed at an earlier stage and have a better prognosis than those with other non-small cell lung cancers. Histologically, the tumor morphology is indistinguishable from undifferentiated carcinoma of the nasopharynx. It is characterized by nests or diffuse sheets of syncytial tumor cells, which show round to oval vesicular nuclei with prominent nucleoli, along with an admixed heavy lymphocytic and plasma cell infiltrate. The presence of Epstein-Barr virus in the tumor cells is crucial for the diagnosis. The differential diagnoses include lymphoepithelioma-like carcinoma from other sites and pulmonary involvement of lymphoma. EGFR mutations and ALK rearrangements are not commonly found in lymphoepithelioma-like carcinoma, in contrast to programmed death ligand-1 expression, which is shown in a majority of cases.
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Affiliation(s)
- Sakda Sathirareuangchai
- From the Department of Pathology, John A. Burns School of Medicine, University of Hawaii, Honolulu
| | - Kirk Hirata
- From the Department of Pathology, John A. Burns School of Medicine, University of Hawaii, Honolulu
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6
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Wang L, Dong H, Ni S, Huang D, Tan C, Chang B, Sheng W. Programmed death-ligand 1 is upregulated in intrahepatic lymphoepithelioma-like cholangiocarcinoma. Oncotarget 2018; 7:69749-69759. [PMID: 27626174 PMCID: PMC5342512 DOI: 10.18632/oncotarget.11949] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Accepted: 09/02/2016] [Indexed: 01/10/2023] Open
Abstract
Intrahepatic lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare variant of cholangiocarcinoma. Here, we report the largest single series of LELCC cases yet studied (n = 13). We retrospectively analyzed the clinical data of the 13 patients and measured the expression of programmed death-ligand 1 (PD-L1) in tumors using immunohistochemical staining. We also analyzed 15 cases of conventional intrahepatic cholangiocarcinoma (IHCC) for comparison. We found that eight patients with LELCC were infected with Epstein-Barr Virus (EBV), and EBV infection correlated with poor prognosis in LELCC. Four patients among the five (80.0%) without EBV had a history of chronic viral hepatitis B. None of the 15 cases of conventional cholangiocarcinoma were positive for EBV. PD-L1 was expressed in both the tumor cells and tumor-infiltrating immune cells in LELCC patients at higher levels than in IHCC patients (P < 0.05). These observations suggest that EBV infection may promote the development of LELCC, and that PD-L1 may be a potential therapeutic target for treatment of EBV-associated LELCC.
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Affiliation(s)
- Lei Wang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Hui Dong
- Department of Pathology, Shanghai Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, 200438, China
| | - Shujuan Ni
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Dan Huang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Cong Tan
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Bin Chang
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Weiqi Sheng
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
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Díaz Del Arco C, Esteban Collazo F, Fernández Aceñero MJ. Lymphoepithelioma-like carcinoma of the large intestine: A case report and literature review. REVISTA ESPANOLA DE PATOLOGIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE ANATOMIA PATOLOGICA Y DE LA SOCIEDAD ESPANOLA DE CITOLOGIA 2018; 51:18-22. [PMID: 29290316 DOI: 10.1016/j.patol.2017.08.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Revised: 07/31/2017] [Accepted: 08/18/2017] [Indexed: 06/07/2023]
Abstract
Lymphoepithelioma like carcinoma (LELC) is a well-known neoplastic lesion that mainly involves the stomach and which has been linked to Epstein Barr virus infection. There are exceptional cases of intestinal involvement by LELC, with 7 reported cases to date. We report a new case of LELC affecting the right colon and review the literature on this rare disorder, with special emphasis on pathogenesis, molecular features and differential diagnosis.
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8
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Crescenzi A, Taffon C, Donati M, Guarino MPL, Valeri S, Coppola R. PD-L1/PD-1 check-point in gastric carcinoma with lymphoid stroma case report with immunochemical study. Medicine (Baltimore) 2017; 96:e5730. [PMID: 28207501 PMCID: PMC5319490 DOI: 10.1097/md.0000000000005730] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
INTRODUCTION Gastric carcinoma with lymphoid stroma is an unusual type of gastric tumor associated with a better prognosis than typical gastric carcinomas. The hallmark of this cancer is a prominent lymphoid infiltration of the stroma that represents an intense host lymphocytic response. The programmed death 1-programmed death-ligand 1 (PD-1/PD-L1) axis has recently emerged as a master immune checkpoint that controls antitumor immune responses against many neoplasms. PATIENT'S CONCERNS CASE STUDY AND OUTCOME We report the case of a male patient with gastric carcinoma with lymphoid stroma with a large mass infiltrating the gastric wall without nodal metastasis. He is alive without disease 10 months after surgery. We focused the study on factors that potentially modulate the prognosis. In this setting we demonstrate, for the first time in this type of tumor, by immunohistochemistry a strong PD-L1 expression in neoplastic cell and the presence of PD-1 positive infiltrating lymphocytes. CONCLUSION The applied approach may contribute to the knowledge about host reaction in such tumor and it may also be used for tumor precise identification on the endoscopic biopsy time before excision surgery.
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Affiliation(s)
| | | | | | | | - Sergio Valeri
- Surgical Unit, University Hospital Campus Bio-Medico, Rome, Italy
| | - Roberto Coppola
- Surgical Unit, University Hospital Campus Bio-Medico, Rome, Italy
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9
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Xu Q, DU J, Liu B. Lymphoepithelioma-like gastric carcinoma located in the lesser curvature of the gastric body: A case report and review of the literature. Mol Clin Oncol 2016; 4:405-408. [PMID: 26998292 DOI: 10.3892/mco.2015.717] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Accepted: 12/08/2015] [Indexed: 12/21/2022] Open
Abstract
Lymphoepithelioma-like gastric carcinoma (LELC) is a type of Epstein-Barr virus (EBV)-associated gastric cancer, characterized by the presence of a lymphoid stroma with cells arranged primarily in microalveolar, thin trabecular and primitive tubular patterns, or isolated cells. In situ hybridization is usually used to confirm the presence of EBV. LELC is a rare type of cancer, with an incidence of 1-4% among all gastric cancers. Despite its rarity, this tumor has attracted attention due to its distinct clinicopathological characteristics and its association with the immune system. This is the report of a rare case of gastric LELC located in the lesser curvature of the gastric body.
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Affiliation(s)
- Qiuping Xu
- Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, P.R. China
| | - Juan DU
- Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China
| | - Baorui Liu
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu 210008, P.R. China
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Wang ZH, Zhao JJ, Yuan Z. Lymphoepithelioma-like gastric carcinoma: A case report and review of the literature. World J Gastroenterol 2016; 22:3056-3061. [PMID: 26973402 PMCID: PMC4779929 DOI: 10.3748/wjg.v22.i10.3056] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Revised: 07/27/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Lymphoepithelioma-like gastric carcinoma is a rare type of gastric cancer characterized by a carcinoma with intense stromal lymphocytic infiltration. Although lymphocytic infiltration is closely associated with Epstein-Barr virus (EBV) infection, concomitant occurrence with differentiated adenocarcinoma is relatively rare. The clinical manifestations of lymphoepithelioma-like gastric carcinoma (including EBV-positive and -negative forms) are similar to those of gastric cancer, and the diagnosis is based on pathologic, histologic, and immunohistochemical findings. This report describes the case of a 55-year-old female patient who presented with a 10-year history of recurrent and worsening abdominal pain and melena that had been occurring for 2 mo. An ulcerative lesion was detected in the stomach by endoscopic examination, which raised suspicion of early gastric cancer. A subsequent preoperative endoscopic biopsy showed adenocarcinoma, but the postoperative pathologic, histologic, and immunohistochemical analyses of the resected specimen revealed a final diagnosis of lymphoepithelioma-like gastric carcinoma.
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11
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Computed tomography findings for a gastric lymphoepithelioma-like carcinoma: How often does it present as a submucosal mass? Eur Radiol 2015; 26:3077-85. [DOI: 10.1007/s00330-015-4122-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 11/13/2015] [Accepted: 11/16/2015] [Indexed: 12/11/2022]
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12
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Solinas A, Calvisi DF. Lessons from rare tumors: Hepatic lymphoepithelioma-like carcinomas. World J Gastroenterol 2015; 21:3472-3479. [PMID: 25834311 PMCID: PMC4375568 DOI: 10.3748/wjg.v21.i12.3472] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Revised: 12/11/2014] [Accepted: 02/05/2015] [Indexed: 02/06/2023] Open
Abstract
In this review we focus on lymphoepithelioma-like hepatocellular carcinomas (LEL-HCC) and lymphoepithelioma-like cholangiocarcinomas (LEL-ICC). Despite their rarity, these tumors are of general interest because of their epidemiological and clinical features, and because they represent a distinct model of interaction between the immune system and neoplastic cells. Approximately half of LEL-HCC arise in the context of chronic hepatitis C virus (HCV) infection and have been described both in Eastern and Western patients. By contrast, LEL-ICC is associated in almost all cases with Epstein-Barr virus (EBV) infection and exhibits the same epidemiological features of EBV related malignancies. Compared with classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma of corresponding stage, both LEL-HCC and LEL-ICC are characterized by lower rates of recurrence after surgery and better overall survival. How this behavior is related to distinct genetic alterations and tumor microenvironment is unclear. The pathophysiological mechanisms of lymphoid infiltrations seem to be different among the two groups of tumors. In fact, LEL-HCC frequently arises in the context of inflammatory changes driven by HCV infection, and has been recognized as a variant of classical hepatocellular carcinoma. At variance, lymphocyte recruitment of LEL-ICC is similar to that described in nasopharyngeal carcinoma and gastric LEL, and possibly depends on the expression pattern of latent EBV infection.
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Genitsch V, Novotny A, Seiler CA, Kröll D, Walch A, Langer R. Epstein-barr virus in gastro-esophageal adenocarcinomas - single center experiences in the context of current literature. Front Oncol 2015; 5:73. [PMID: 25859432 PMCID: PMC4374449 DOI: 10.3389/fonc.2015.00073] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2014] [Accepted: 03/11/2015] [Indexed: 12/14/2022] Open
Abstract
Epstein–Barr virus (EBV)-associated gastric carcinomas (GC) represent a distinct and well-recognized subtype of gastric cancer with a prevalence of around 10% of all GC. In contrast, EBV has not been reported to play a major role in esophageal adenocarcinomas (EAC) and adenocarcinomas of the gastro-esophageal junction (GEJ). We report our experiences on EBV in collections of gastro-esophageal adenocarcinomas from two surgical centers and discuss the current state of research in this field. Tumor samples from 465 primary resected gastro-esophageal adenocarcinomas (118 EAC, 73 GEJ, and 274 GC) were investigated. Presence of EBV was determined by EBV-encoded small RNAs (EBER) in situ hybridization. Results were correlated with pathologic parameters (UICC pTNM category, Her2 status, tumor grading) and survival. EBER positivity was observed in 14 cases. None of the EAC were positive for EBER. In contrast, we observed EBER positivity in 2/73 adenocarcinomas of the GEJ (2.7%) and 12/274 GC (4.4%). These were of intestinal type (seven cases) or unclassifiable (six cases), while only one case was of diffuse type according to the Lauren classification. No association between EBV and pT, pN, or tumor grading was found, neither was there a correlation with clinical outcome. None of the EBER positive cases were Her2 positive. In conclusion, EBV does not seem to play a role in the carcinogenesis of EAC. Moreover, adenocarcinomas of the GEJ show lower rates of EBV positivity compared to GC. Our data only partially correlate with previous reports from the literature. This highlights the need for further research on this distinct entity. Recent reports, however, have identified specific epigenetic and genetic alterations in EBV-associated GC, which might lead to a distinct treatment approach for this specific subtype of GC in the future.
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Affiliation(s)
- Vera Genitsch
- Institute of Pathology, University of Bern , Bern , Switzerland
| | - Alexander Novotny
- Department of Surgery, Klinikum Rechts der Isar, Technische Universität München , München , Germany
| | - Christian A Seiler
- Department of Visceral Surgery and Medicine, Inselspital University Hospital Bern, University of Bern , Bern , Switzerland
| | - Dino Kröll
- Department of Visceral Surgery and Medicine, Inselspital University Hospital Bern, University of Bern , Bern , Switzerland
| | - Axel Walch
- German Research Center for Environmental Health, Institute of Pathology, Helmholtz Zentrum München , Neuherberg , Germany
| | - Rupert Langer
- Institute of Pathology, University of Bern , Bern , Switzerland
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