|
1
|
Yang HC, Fu CF, Qiao LJ, Long GH, Yang LF, Yao B. Relationship between Helicobacter pylori infection and programmed death-ligand 1 in gastric cancer: A meta-analysis. World J Clin Oncol 2025; 16:102397. [PMID: 40290698 PMCID: PMC12019281 DOI: 10.5306/wjco.v16.i4.102397] [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: 10/16/2024] [Revised: 12/04/2024] [Accepted: 02/06/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Gastric cancer (GC) is one of the most common malignancies worldwide, and Helicobacter pylori (HP) infection is a well-established risk factor for its development. Programmed death-ligand 1 (PD-L1) expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment. While HP infection and PD-L1 expression in GC may be linked, the relationship between them remains unclear, in part because there have been conflicting results reported from various studies. AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC. METHODS A systematic literature review was conducted using PubMed, Embase, Cochrane Library, and Web of Science databases. Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included. Odds ratios and 95% confidence intervals were calculated to estimate the association. Heterogeneity was assessed using Cochrane's Q test and I² statistic. A random-effects model was used due to significant heterogeneity across studies. RESULTS Fourteen studies involving a total of 3069 patients with GC were included. The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues (odd ratio = 1.69, 95% confidence interval: 1.24-2.29, P < 0.001, I 2 = 59%). Sensitivity analyses confirmed the robustness of these findings. Subgroup analyses did not show significant variation based on geographic region, sample size, or method of PD-L1 assessment. Publication bias was minimal, as shown by funnel plots and Egger's regression test. CONCLUSION HP infection is associated with increased PD-L1 expression in GC, suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.
Collapse
Affiliation(s)
- Hong-Chang Yang
- Department of Gastroenterology, Longgang Central Hospital of Shenzhen, Shenzhen 518100, Guangdong Province, China
| | - Cheng-Feng Fu
- Department of Oncology, Tongren People’s Hospital, Tongren 554300, Guizhou Province, China
| | - Li-Jun Qiao
- Department of Basic Medical Sciences, Guizhou Health Vocational College, Tongren 554300, Guizhou Province, China
| | - Gen-He Long
- Department of School of Medicine, Guizhou Vocational and Technical College, Tongren 554300, Guizhou Province, China
| | - Li-Fen Yang
- Department of Oncology, Tongren People’s Hospital, Tongren 554300, Guizhou Province, China
| | - Biao Yao
- Department of Oncology, Tongren People’s Hospital, Tongren 554300, Guizhou Province, China
| |
Collapse
|
|
2
|
Lee SM, Oh H. Association of PD-L1 positivity with Epstein Barr virus infection and microsatellite instability in gastric carcinomas with lymphoid stroma. Sci Rep 2024; 14:30932. [PMID: 39730741 DOI: 10.1038/s41598-024-81764-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 11/28/2024] [Indexed: 12/29/2024] Open
Abstract
Gastric carcinoma with lymphoid stroma (GCLS) is characterized by dense intra-and peritumoral lymphocytic infiltration and a high rate of Epstein Barr Virus (EBV) infection, suggesting being a promising candidate for immunotherapy. We investigated correlations between PD-L1 expression and clinicopathologic factors, including EBV positivity and microsatellite instability (MSI) status in GCLSs. The study included resected 214 GCLSs and 300 gastric adenocarcinomas (GACs) for control. Epstein Barr Virus encoding region in situ hybridization (EBER ISH), immunohistochemistry for PD-L1 and HER2, dual-colored in situ hybridization for HER2, and MSI analysis were performed. EBV positivity was found in 181 (85%) of 214 GCLSs. MSI analysis demonstrated that 0.6% of EBV + GCLSs and 54.5% of EBV-GCLSs were MSI-high compared to 7% of EBV-GACs. Approximately 3% and 3.9% of HER2 amplifications were found in EBV- and EBV + GCLSs compared to 13% of EBV-GACs. PD-L1 expression with ≥ 1, ≥ 5, and ≥ 10 combined positive scores (CPS) were observed in 81.8%, 70.2%, and 55.3% of EBV + GCLSs. PD-L1 expression with ≥ 10 CPS was observed in 21.2% of EBV-GCLSs, predominantly in MSI-H tumors (85.7%). EBV positivity and MSI are associated with PD-L1 positivity rates in patients with GCLS who may respond better to PD-1/PD-L1 inhibitors but not anti-HER2 inhibitors.
Collapse
Affiliation(s)
- Sun Mi Lee
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 W. 11th street, Indianapolis, IN, 46202, USA.
- Department of Pathology, Jeju National University Hospital, Jeju-si, South Korea.
| | - Hyunjoo Oh
- Department of Internal Medicine, Jeju National University Hospital, Jeju-si, South Korea
| |
Collapse
|
|
3
|
Porav-Hodade D, Gherasim R, Loghin A, Lazar B, Cotoi OS, Badea MA, Ilona MOK, Todea-Moga C, Vartolomei MD, Rares G, Crisan N, Feciche OB. Bladder Adenocarcinoma in a Constellation of Multiple Site Malignancies: An Unusual Case and Systematic Review. Diagnostics (Basel) 2024; 14:2510. [PMID: 39594177 PMCID: PMC11592427 DOI: 10.3390/diagnostics14222510] [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: 10/14/2024] [Revised: 11/05/2024] [Accepted: 11/08/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Multiple primary malignant tumors represent a small percentage of the total number of oncological cases and can involve either metachronous or synchronous development and represent challenges in diagnosis, staging, and treatment planning. Our purpose is to present a rare case of bladder adenocarcinoma in a female patient with multiple primary malignant tumors and to provide systematic review of the available literature. MATERIALS AND METHODS A 67-year-old female patient was admitted with altered general condition and anuria. The past medical history of the patient included malignant melanoma (2014), cervical cancer (2017), colon cancer (2021), obstructive anuria (2023), and liver metastasectomy (2023). Transurethral resection of bladder tumor was performed for bladder tumors. RESULTS Contrast CT highlighted multiple pulmonary metastases, a poly nodular liver conglomerate, retroperitoneal lymph node, II/III grade left ureterohydronephrosis, and no digestive tract tumor masses. The pathological result of the bladder resection showed an infiltrative adenocarcinoma. CONCLUSIONS The difference between primary bladder adenocarcinoma tumor and metastatic colorectal adenocarcinoma is the key for the future therapeutic strategy. Identification and assessment of risk factors such as viral infection, radiotherapy, chemotherapy, smoking, and genetics are pivotal in understanding and managing multiple primary malignant tumors. Personalized prevention strategies and screening programs may facilitate the early detection of these tumors, whether synchronous or metachronous. The use of multicancer early detection (MCED) blood tests for early diagnosis appears promising. However, additional research is needed to standardize these techniques for cancer detection.
Collapse
Affiliation(s)
- Daniel Porav-Hodade
- Department of Urology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania; (D.P.-H.); (M.O.K.I.)
- Department of Urology, Clinical County Hospital Mures, 540136 Târgu Mures, Romania;
| | - Raul Gherasim
- Department of Urology, Clinical County Hospital Mures, 540136 Târgu Mures, Romania;
| | - Andrada Loghin
- Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania; (A.L.); (O.S.C.)
- Department of Pathophysiology, Clinical County Hospital Mures, 540136 Târgu Mures, Romania;
| | - Bianca Lazar
- Department of Pathophysiology, Clinical County Hospital Mures, 540136 Târgu Mures, Romania;
| | - Ovidiu Simion Cotoi
- Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania; (A.L.); (O.S.C.)
- Department of Pathophysiology, Clinical County Hospital Mures, 540136 Târgu Mures, Romania;
| | - Mihail-Alexandru Badea
- Department of Dermatology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania;
- Department of Dermatology, Clinical County Hospital Mures, 540136 Târgu Mures, Romania
| | - Mártha Orsolya Katalin Ilona
- Department of Urology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania; (D.P.-H.); (M.O.K.I.)
- Department of Urology, Clinical County Hospital Mures, 540136 Târgu Mures, Romania;
| | - Ciprian Todea-Moga
- Department of Urology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania; (D.P.-H.); (M.O.K.I.)
- Department of Urology, Clinical County Hospital Mures, 540136 Târgu Mures, Romania;
| | - Mihai Dorin Vartolomei
- Department of Cell and Molecular Biology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania;
| | - Georgescu Rares
- Department of General Surgery, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540139 Târgu Mureș, Romania;
- Department of General Surgery, Clinical County Hospital Mures, 540136 Târgu Mures, Romania
| | - Nicolae Crisan
- Department of Urology, Iului Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Ovidiu Bogdan Feciche
- Department of Urology, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania;
- Department of Urology, Emergency County Hospital Oradea, 410169 Oradea, Romania
| |
Collapse
|
|
4
|
Bos J, Groen-van Schooten TS, Brugman CP, Jamaludin FS, van Laarhoven HWM, Derks S. The tumor immune composition of mismatch repair deficient and Epstein-Barr virus-positive gastric cancer: A systematic review. Cancer Treat Rev 2024; 127:102737. [PMID: 38669788 DOI: 10.1016/j.ctrv.2024.102737] [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: 02/13/2024] [Revised: 04/16/2024] [Accepted: 04/19/2024] [Indexed: 04/28/2024]
Abstract
BACKGROUND Gastric cancer (GC), known for its unfavorable prognosis, has been classified in four distinct molecular subtypes. These subtypes not only exhibit differences in their genome and transcriptome but also in the composition of their tumor immune microenvironment. The microsatellite instable (MSI) and Epstein-Barr virus (EBV) positive GC subtypes show clear clinical benefits from immune checkpoint blockade, likely due to a neoantigen-driven and virus-driven antitumor immune response and high expression of immune checkpoint molecule PD-L1. However, even within these subtypes response to checkpoint inhibition is variable, which is potentially related to heterogeneity in the tumor immune microenvironment (TIME) and expression of co-inhibitory molecules. We conducted a systematic review to outline the current knowledge about the immunological features on the TIME of MSI and EBV + GCs. METHODS A systematic search was performed in PubMed, EMBASE and Cochrane Library. All articles from the year 1990 and onwards addressing immune features of gastric adenocarcinoma were reviewed and included based on predefined in- and exclusion criteria. RESULTS In total 5962 records were screened, of which 139 were included that reported immunological data on molecular GC subtypes. MSI and EBV + GCs were reported to have a more inflamed TIME compared to non-MSI and EBV- GC subtypes. Compared to microsatellite stable (MSS) tumors, MSI tumors were characterized by higher numbers of CD8 + and FoxP3 + T cells, and tumor infiltrating pro- and anti-inflammatory macrophages. HLA-deficiency was most common in MSI tumors compared to other molecular GC subtypes and associated with lower T and B cell infiltrates compared to HLA-proficient tumors. EBV + was associated with a high number of CD8 + T cells, Tregs, NK cells and macrophages. Expression of PD-L1, CTLA-4, Granzyme A and B, Perforin and interferon-gamma was enriched in EBV + tumors. Overall, MSI tumors harbored a more heterogeneous TIME in terms of immune cell composition and immune checkpoints compared to the EBV + tumors. DISCUSSION AND CONCLUSION MSI and EBV + GCs are highly Handbook for Conducting a Literature-Based Health Assessment Using OHAT Approach for Systematic Review and Evidence Integration.; 2019pro-inflammatory immune cell populations. Although studies on the direct comparison of EBV + and MSI tumors are limited, EBV + tumors show less intra-subgroup heterogeneity compared to MSI tumors. More studies are needed to identify how Intra-subgroup heterogeneity impacts response to immunotherapy efficacy.
Collapse
Affiliation(s)
- J Bos
- Amsterdam UMC Location University of Amsterdam, Department of Medical Oncology, Meibergdreef 9, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands
| | - T S Groen-van Schooten
- Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Medical Oncology, De Boelelaan 1117, Amsterdam, the Netherlands
| | - C P Brugman
- Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Medical Oncology, De Boelelaan 1117, Amsterdam, the Netherlands
| | - F S Jamaludin
- Amsterdam UMC Location University of Amsterdam, Medical Library AMC, Meibergdreef 9, Amsterdam, the Netherlands
| | - H W M van Laarhoven
- Amsterdam UMC Location University of Amsterdam, Department of Medical Oncology, Meibergdreef 9, Amsterdam, the Netherlands; Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands
| | - S Derks
- Cancer Center Amsterdam, Cancer Biology and Immunology, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Medical Oncology, De Boelelaan 1117, Amsterdam, the Netherlands.
| |
Collapse
|
|
5
|
Dokanei S, Minai‐Tehrani D, Moghoofei M, Rostamian M. Investigating the relationship between Epstein-Barr virus infection and gastric cancer: A systematic review and meta-analysis. Health Sci Rep 2024; 7:e1976. [PMID: 38505684 PMCID: PMC10948593 DOI: 10.1002/hsr2.1976] [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: 08/26/2023] [Revised: 02/06/2024] [Accepted: 02/28/2024] [Indexed: 03/21/2024] Open
Abstract
Background and Aims Gastric cancer (GC) is a common cancer type worldwide, and various factors can be involved in its occurrence. One of these factors is Epstein-Barr virus (EBV) infection. In this regard, a systematic review and meta-analysis was conducted to achieve a better understanding of the EBV prevalence in GC samples. Methods English databases were searched and studies that reported the prevalence and etiological factors of EBV related to GC from July 2007 to November 2022 were retrieved. The reported data were selected based on the inclusion and exclusion criteria. The pooled prevalence of EBV infection with 95% confidence intervals was calculated. Quality assessment, heterogeneity testing, and publication bias assessment were also performed. The literature search showed 953 studies, of which 87 studies met our inclusion criteria and were used for meta-analysis. Results The pooled prevalence of EBV infection related to GC was estimated to be 9.5% (95% confidence interval [CI]: 8.2%-11%) in the general population. The prevalence of EBV infection related to GC by gender was 13.5% (95% CI: 11.1%-16.3%) in males and 7.6% (95% CI: 5.4%-10.6%) in females. No significant differences were observed in terms of geographical region. Out of the 87 studies included in the meta-analysis, the most common diagnostic test was in situ hybridization (58 cases). Conclusions Altogether, the results indicated that EBV infection is one of the important factors in the development of GC. However, this does not necessarily mean that EBV infection directly causes GC since other factors may also be involved in the development of GC. Therefore, it is recommended to conduct extensive epidemiological studies on various aspects of the relationship between this virus and GC, which can provide valuable information for understanding the relationship between EBV and GC.
Collapse
Affiliation(s)
- Saman Dokanei
- Faculty of Life Sciences and BiotechnologyShahid Beheshti University (GC)TehranIran
| | | | - Mohsen Moghoofei
- Department of Microbiology, Faculty of MedicineKermanshah University of Medical SciencesKermanshahIran
| | - Mosayeb Rostamian
- Infectious Diseases Research Center, Health InstituteKermanshah University of Medical SciencesKermanshahIran
- Student Research CommitteeKermanshah University of Medical SciencesKermanshahIran
| |
Collapse
|
|
6
|
Ying T, Chen J, Song J, Zhou Y, Bao B, Zheng L. Prognosis of EBV-positive gastric cancer with lymphoid stroma: systematic review and meta-analysis. Scand J Gastroenterol 2024; 59:316-324. [PMID: 38032298 DOI: 10.1080/00365521.2023.2286194] [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: 09/12/2023] [Revised: 11/06/2023] [Accepted: 11/15/2023] [Indexed: 12/01/2023]
Abstract
BACKGROUND Although gastric cancer with lymphoid stroma (GCLS) presents better prognosis, uncertainty still exists regarding the association of Epstein-Barr virus (EBV) infection with prognosis of GCLS. Therefore, it is urgent to evaluate the outcome and characteristics of EBV-positive GCLS via a systematic review and meta-analysis. METHODS Three medical databases, with a period ranging from 2000 to so far, were searched for observational studies on EBV infection, clinical characteristics and prognosis. Odds ratio (OR) was used to evaluate the mortality and clinical characteristics of EBV-positive GCLS patients. Egger's test and subgroup analysis were conducted to identify the source of heterogeneity. RESULTS Nine retrospective studies were finally identified, which involved 618 EBV-positive and 153 EBV-negative GCLS patients. The forest plot indicated that EBV-positive GCLS patients had lower mortality (p = .009; 95% CI: 0.15-0.77; I2 = 48.6%). Both of funnel plot and Egger's tests suggested that there was no publication bias. Nonetheless, subgroup analysis indicated that T1-2 stage ratio more than 50% (p < .001; I2 = 6.7%) and male ratio more than 80% (p < .001; I2 = 0.0%) were valuable for eliminating the heterogeneity. Seven studies including valid information showed that TNM stage of EBV-positive and negative GCLS patients was not statistically different (p = .644; 95% CI: 0.50-1.53; I2 = 0.0%). CONCLUSIONS EBV-positive GCLS tends to have lower mortality, suggesting that detection of EBV infection is necessary to predict prognosis of GCLS.
Collapse
Affiliation(s)
- Tianxin Ying
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Jie Chen
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Jiyu Song
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Yi Zhou
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Banghe Bao
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Liduan Zheng
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Clinical Center of Human Genomic Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| |
Collapse
|
|
7
|
Mostaghimi T, Bahadoran E, Bakht M, Taheri S, Sadeghi H, Babaei A. Role of lncRNAs in Helicobacter pylori and Epstein-Barr virus associated gastric cancers. Life Sci 2024; 336:122316. [PMID: 38035995 DOI: 10.1016/j.lfs.2023.122316] [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: 09/30/2023] [Revised: 11/17/2023] [Accepted: 11/27/2023] [Indexed: 12/02/2023]
Abstract
Helicobacter pylori infection is a risk factor for the development of gastric cancer (GC), and the role of co-infection with viruses, such as Epstein-Barr virus, in carcinogenesis cannot be ignored. Furthermore, it is now known that genetic factors such as long non-coding RNAs (lncRNAs) are involved in many diseases, including GC. On the other side, they can also be used as therapeutic goals. Modified lncRNAs can cause aberrant expression of genes encoding proximal proteins, which are essential for the development of carcinoma. In this review, we present the most recent studies on lncRNAs in GC, concentrating on their roles in H. pylori and EBV infections, and discuss some of the molecular mechanisms of these GC-related pathogens. There was also a discussion of the research gaps and future perspectives.
Collapse
Affiliation(s)
- Talieh Mostaghimi
- Department of Medical Microbiology and Biotechnology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Ensiyeh Bahadoran
- School of Medicine, Qazvin University of Medical Science, Qazvin, Iran
| | - Mehdi Bakht
- Medical Microbiology Research Center, Qazvin University of Medical Science, Qazvin, Iran
| | - Shiva Taheri
- Medical Microbiology Research Center, Qazvin University of Medical Science, Qazvin, Iran
| | - Hamid Sadeghi
- Medical Microbiology Research Center, Qazvin University of Medical Science, Qazvin, Iran
| | - Abouzar Babaei
- Medical Microbiology Research Center, Qazvin University of Medical Science, Qazvin, Iran.
| |
Collapse
|
|
8
|
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.
Collapse
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
| |
Collapse
|
|
9
|
Mundo L, Leoncini L, Accardi-Gheit R. Epstein-Barr Virus Infection in Cancer. Cancers (Basel) 2023; 15:4659. [PMID: 37760627 PMCID: PMC10526860 DOI: 10.3390/cancers15184659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 06/06/2023] [Indexed: 09/29/2023] Open
Abstract
EBV was the first human oncogenic virus identified [...].
Collapse
Affiliation(s)
- Lucia Mundo
- Health Research Institute, School of Medicine, University of Limerick, V94 T9PX Limerick, Ireland
- Section of Pathology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
| | - Lorenzo Leoncini
- Section of Pathology, Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
| | - Rosita Accardi-Gheit
- Section of Mechanisms of Carcinogenesis, International Agency for Research on Cancer, World Health Organization, 69366 Lyon, France
| |
Collapse
|
|
10
|
Wu CH, Lai CL, Teng CLJ, Fang WL, Huang KH, Fen-Yau Li A, Yu HY, Chiang NJ, Chao Y, Hung YP, Chen MH. Immunoprofile of adenosquamous carcinoma in gastric cancer. J Chin Med Assoc 2023; 86:542-548. [PMID: 36989495 DOI: 10.1097/jcma.0000000000000922] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/31/2023] Open
Abstract
BACKGROUND Gastric adenosquamous carcinoma (GASC) is a rare subtype of gastric cancer. Research on GASC treatment is limited, and its outcome is usually poor. We investigated the clinical features, immunoprofile of GASC, and determined the optimal treatment modality for these patients. METHODS Patients with GASC from Taipei Veterans General Hospital were retrospectively reviewed. Clinical features and treatment outcomes were evaluated. Adequate samples were examined for surrogate biomarkers for immunotherapy by IHC staining. RESULTS Total 14 (0.35%) GASC patients were found among 4034 gastric cancer patients. The median tumor size was 6.8 cm in 10 patients with stage III GASC, and all these patients underwent radical gastrectomy followed by adjuvant therapy. The median progression-free survival (PFS) and overall survival (OS) were 6.0 and 11.5 months, respectively. Two patients with stage IV GASC received frontline immunotherapy. Their median PFS and OS were 9.0 and 12.5 months. In immunoprofiling, 25.0% (n = 3), 75.0% (n = 9), and 33.3% (n = 4) of the samples had deficient mismatch repair (dMMR) protein, combined positive score (CPS) of ≥1, and CPS of ≥10, respectively. The univariate analysis revealed that programmed death-ligand 1 ≥5% (HR: 0.12; 95% CI: 0.01-0.97; p = 0.047) was significant associated with superior OS. One stage IV patient with CPS ≥10 and dMMR proteins received nivolumab monotherapy as frontline treatment that resulted 14-month PFS. CONCLUSION Patients with GASC are more likely to yield positive results for CPS and dMMR. Biomarkers should be examined, and immunotherapy can be considered as frontline systemic treatment.
Collapse
Affiliation(s)
- Cheng-Han Wu
- Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
| | - Cheng-Lun Lai
- Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
| | - Chieh-Lin Jerry Teng
- Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
- Department of Life Science, Tunghai University, Taichung, Taiwan, ROC
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC
- College of Medicine, National Chung Hsing University, Taichung, Taiwan, ROC
| | - Wen-Liang Fang
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Kuo-Hung Huang
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Anna Fen-Yau Li
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Department of Pathology, Cheng Hsin General Hospital, Taipei, Taiwan, ROC
| | - Hung-Yuan Yu
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Hospitalist Ward, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Nai-Jung Chiang
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Yee Chao
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Yi-Ping Hung
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Ming-Huang Chen
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| |
Collapse
|
|
11
|
Pyo JS, Kim NY, Kang DW. Prognostic Implication of EBV Infection in Gastric Carcinomas: A Systematic Review and Meta-Analysis. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:834. [PMID: 37241066 PMCID: PMC10221611 DOI: 10.3390/medicina59050834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 04/12/2023] [Accepted: 04/18/2023] [Indexed: 05/28/2023]
Abstract
Background and objectives: This study aims to elucidate the prognostic implications of Epstein-Barr virus (EBV) infection in gastric carcinomas (GCs) through a systematic review and meta-analysis. Materials and Methods: In total, 57 eligible studies and 22,943 patients were included in this meta-analysis. We compared the prognoses of EBV-infected and non-infected GC patients. The subgroup analysis was performed based on the study location, molecular classification, and Lauren's classification. This study was checked according to the PRISMA 2020. The meta-analysis was performed using the Comprehensive Meta-Analysis software package. Results: EBV infection was found in 10.4% (95% confidence interval (CI) 0.082-0.131) of GC patients. The EBV-infected GC patients had a better overall survival compared with the EBV-non-infected GC patients (hazard ratio (HR) 0.890, 95% CI 0.816-0.970). In the subgroup analysis based on molecular classification, no significant differences were found between EBV+ and microsatellite instability and microsatellite stable (MSS)/EBV- subgroups (HR 1.099, 95% CI 0.885-1.364 and HR 0.954, 95% CI 0.872-1.044, respectively). In the diffuse type of Lauren's classification, EBV-infected GCs have a better prognosis compared with the EBV-non-infected GCs (HR 0.400, 95% CI 0.300-0.534). The prognostic impact of EBV infection was found in the Asian and American subgroups but not in the European subgroup (HR 0.880, 95% CI 0.782-0.991, HR 0.840, 95% CI 0.750-0.941, and HR 0.915, 95% CI 0.814-1.028). Conclusions: EBV infection is a favorable survival factor for GCs. However, the prognostic implications of EBV infection in the new molecular classification are not clear.
Collapse
Affiliation(s)
- Jung-Soo Pyo
- Department of Pathology, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Republic of Korea
| | - Nae-Yu Kim
- Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu-si 11759, Republic of Korea
| | - Dong-Wook Kang
- Department of Pathology, Chungnam National University Sejong Hospital, 20 Bodeum 7-ro, Sejong-si 30099, Republic of Korea
- Department of Pathology, Chungnam National University School of Medicine, 266 Munhwa Street, Daejeon 35015, Republic of Korea
| |
Collapse
|
|
12
|
Hirabayashi M, Georges D, Clifford GM, de Martel C. Estimating the Global Burden of Epstein-Barr Virus-Associated Gastric Cancer: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol 2023; 21:922-930.e21. [PMID: 35963539 DOI: 10.1016/j.cgh.2022.07.042] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 07/29/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Evidence suggests that a fraction of new gastric cancer cases may be etiologically associated with Epstein-Barr virus (EBV), a known carcinogenic agent. We aimed to systematically explore the proportion of EBV-positive gastric cancer. METHODS We did a systematic review (PROSPERO CRD42020164473) from January 1990 to August 2021. For each country and geographical region with available data, pooled prevalence and corresponding 95% confidence intervals (CIs) of EBV in gastric tumors were calculated for 3 subtypes of gastric adenocarcinoma (conventional adenocarcinoma, lymphoepithelioma-like gastric carcinoma, and remnant/stump carcinoma). For conventional adenocarcinoma, prevalence ratios (PRs) were presented for sex, Lauren's classification, gastric cancer stage, and anatomical location of the stomach. RESULTS In 220 eligible studies including over 68,000 cases of conventional gastric adenocarcinoma, EBV prevalence in tumor cells was 7.5% (95% CI, 6.9%-8.1%) and was higher in men compared with women (PR, 2.1; 95% CI, 1.9-2.4), in diffuse type compared with intestinal type (PR, 1.3; 95% CI, 1.1-1.5), and in the proximal region compared with the distal region (PR, 2.5; 95% CI, 2.0-3.1). There was no difference in EBV prevalence by gastric cancer stage. EBV prevalence was 75.9% (95% CI, 62.8%-85.5%) among lymphoepithelioma-like gastric carcinoma and 26.3% (95% CI, 22.2%-32.0%) among remnant or stump carcinoma. CONCLUSIONS Assuming a causal association between EBV and gastric cancer, our findings, when applied to the GLOBOCAN 2020 gastric cancer incidence, suggest that primary prevention such as the development of an effective EBV vaccine might prevent 81,000 EBV-associated gastric cancer cases worldwide annually.
Collapse
Affiliation(s)
- Mayo Hirabayashi
- Early Detection, Prevention and Infections Branch, International Agency for Research on Cancer, Lyon, France
| | - Damien Georges
- Early Detection, Prevention and Infections Branch, International Agency for Research on Cancer, Lyon, France
| | - Gary M Clifford
- Early Detection, Prevention and Infections Branch, International Agency for Research on Cancer, Lyon, France
| | - Catherine de Martel
- Early Detection, Prevention and Infections Branch, International Agency for Research on Cancer, Lyon, France.
| |
Collapse
|
|
13
|
An G, He XC, Bai J, Wang J. Immune checkpoint inhibitors are effective in the treatment of Epstein-Barr virus-associated gastric cancer: A case report. Medicine (Baltimore) 2023; 102:e33377. [PMID: 37000076 PMCID: PMC10063274 DOI: 10.1097/md.0000000000033377] [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: 02/04/2023] [Accepted: 03/08/2023] [Indexed: 04/01/2023] Open
Abstract
RATIONALE Gastric cancer (GC) is one of the most common malignancies globally, and its occurrence and development are associated with genetic, dietary, biological, and immune factors. Epstein-Barr virus-associated gastric cancer (EBVaGC), as a special subtype of GC, has become a research hotspot in recent years. In patients with advanced GC, Epstein-Barr virus infection is closely related to lymph node metastasis, depth of tumor invasion, and poor prognosis. There is great clinical need for a new treatment modality for EBVaGC. Advances in molecular biology and cancer genetics have led to the development of immune checkpoint inhibitors (ICIs); patients treated with ICIs experience clinical benefit and few adverse effects. PATIENT CONCERNS AND DIAGNOSES We report a 31-year-old male with advanced EBVaGC and multiple sites of lymph node metastasis who was intolerant to multiple lines of chemotherapy. INTERVENTIONS AND OUTCOME After immune checkpoint inhibitor treatment, both primary and metastatic tumors shrank significantly without noticeable adverse reactions. After 21 months of progression-free status, the patient underwent R0 resection. LESSONS This case report provides evidence for the use of ICIs in treating EBVaGC. It also shows that detection of Epstein-Barr virus-encoded small nuclear RNA may be a prognostic factor in gastric cancer.
Collapse
Affiliation(s)
- Gaili An
- Department of Internal Medicine Oncology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, China
| | - Xin Cheng He
- Department of Internal Medicine Oncology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, China
| | - Jun Bai
- Department of Internal Medicine Oncology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, China
| | - Jianhua Wang
- Department of General Surgery, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, China
| |
Collapse
|
|
14
|
Zhu Y, Zhu F, Ba H, Chen J, Bian X. Helicobacter pylori infection and PD-L1 expression in gastric cancer: A meta-analysis. Eur J Clin Invest 2023; 53:e13880. [PMID: 36164962 DOI: 10.1111/eci.13880] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 09/24/2022] [Accepted: 09/26/2022] [Indexed: 01/29/2023]
Abstract
BACKGROUND High expression of programmed death ligand-1 (PD-L1) has been related to good response to immunotherapy patients with gastric cancer (GC). However, the influence of Helicobacter pylori (HP) infection on PD-L1 expression in GC remains unknown. A meta-analysis was performed to evaluate the association between HP infection and PD-L1 expression in GC. METHODS Observational studies that investigated the relationship between HP infection and PD-L1 expression in patients with GC were obtained by search electronic databases, including PubMed, Embase, Cochrane's Library and Web of Science. A random-effect model incorporating the possible influence of between-study heterogeneity was used to pool the results. RESULTS Ten studies with 1870 patients with GC contributed to the meta-analysis. Pooled results showed that HP infection was significantly associated with the tumour expression of PD-L1 (odds ratio [OR]: 1.90, 95% confidence interval: 1.33-2.72, p < .001; I2 = 53%). Subgroup analyses showed that the association between HP infection and PD-L1 expression in GC was not significantly affected by sample size, methods for PD-L1 evaluation and quality score (p for subgroup analyses all >.05). However, a stronger association was observed in studies with higher prevalence of HP infection (≥35%, OR: 2.58) as compared with those with lower prevalence (<35%, OR: 1.45, p for subgroup difference = .04). CONCLUSION Helicobacter pylori infection in GC patients is associated with tumour expression of PD-L1, suggesting HP infection may be a predictor of good response to immunotherapy in GC.
Collapse
Affiliation(s)
- Yaodong Zhu
- Department of Integrated Traditional and Western Medicine in Oncology, The First Affiliated Hospital of Medical University of Anhui, Hefei, China
| | - Fangyuan Zhu
- Department of Integrated Traditional and Western Medicine in Oncology, The First Affiliated Hospital of Medical University of Anhui, Hefei, China
| | - He Ba
- Department of Integrated Traditional and Western Medicine in Oncology, The First Affiliated Hospital of Medical University of Anhui, Hefei, China
| | - Jie Chen
- Department of Integrated Traditional and Western Medicine in Oncology, The First Affiliated Hospital of Medical University of Anhui, Hefei, China
| | - Xiuliang Bian
- Department of Integrated Traditional and Western Medicine in Oncology, The First Affiliated Hospital of Medical University of Anhui, Hefei, China
| |
Collapse
|
|
15
|
van der Sluis K, van Sandick JW, van Dieren JM, Vollebergh MA, Grootscholten C, van den Berg JG, Snaebjornsson P, Hartemink KJ, Veenhof AAFA, Chalabi M, Kodach LL. The clinical impact of testing for biomarkers in gastric cancer patients: a real-world cohort. Histopathology 2023; 82:826-836. [PMID: 36694277 DOI: 10.1111/his.14869] [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: 11/04/2022] [Revised: 01/16/2023] [Accepted: 01/18/2023] [Indexed: 01/26/2023]
Abstract
BACKGROUND AND AIMS In gastric cancer (GC), HER2 was the first biomarker for guided therapy registered for clinical use. Considering the recent approvals of immune check-point blockade (ICB) in gastro-oesophageal cancers, testing for mismatch repair deficiency (dMMR), Epstein-Barr virus (EBV) and PD-L1 combined positive score (CPS) is becoming increasingly important. Here we describe a real-world cohort on biomarker assessment in GC patients. METHODS Patients diagnosed with GC between 2017 and 2021 were included. Biomarker results were retrieved from electronic patient files. PD-L1 CPS was determined retrospectively on dMMR and EBV-positive (EBV+) tumours. Data on genomic sequencing were analysed separately. RESULTS Of 363 patients identified, 45% had metastatic disease. In 335 patients (92%) at least one biomarker was tested. The prevalence of HER2+, dMMR and EBV+ tumours was 10% (32 of 319), 7% (20 of 294) and 1% (three of 235), respectively. Of the dMMR and EBV+ tumours, 95% had a PD-L1 CPS ≥ 5. Therapeutic strategy was adjusted in 31 of 55 patients and consisted of anti-HER2 therapies as well as ICB in clinical trials. Genomic alterations were found in 44 of 60 tested patients. TP53 (73%) and PIK3CA (20%) mutations were most common, followed by KRAS mutations (11%) and amplifications (11%). CONCLUSIONS In this real-world cohort, testing for HER2, dMMR and EBV status affected treatment decisions in 56% of the patients. Although most dMMR and EBV+ tumours had a PD-L1 CPS ≥ 5, not all patients with a high probability of treatment response are identified. Based on these results, a stepwise diagnostic strategy is proposed.
Collapse
Affiliation(s)
- Karen van der Sluis
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.,Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Johanna W van Sandick
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Jolanda M van Dieren
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Marieke A Vollebergh
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Cecile Grootscholten
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - José G van den Berg
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Petur Snaebjornsson
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Koen J Hartemink
- Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | | | - Myriam Chalabi
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Liudmila L Kodach
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| |
Collapse
|
|
16
|
Li L, Huang W, Hou P, Li W, Feng M, Liu Y, Gao J. A computed tomography-based preoperative risk scoring system to distinguish lymphoepithelioma-like gastric carcinoma from non-lymphoepithelioma-like gastric carcinoma. Front Oncol 2022; 12:872814. [PMID: 36185305 PMCID: PMC9522524 DOI: 10.3389/fonc.2022.872814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 08/22/2022] [Indexed: 11/30/2022] Open
Abstract
Purpose The aim of this study was to develop a preoperative risk scoring model for distinguishing lymphoepithelioma-like gastric carcinoma (LELGC) from non-LELGC based on contrast-enhanced computed tomography (CT) images. Methods Clinicopathological features and CT findings of patients with LELGC and non-LELGC in our hospital from January 2016 to July 2022 were retrospectively analyzed and compared. A preoperative risk stratification model and a risk scoring system were developed using logistic regression. Results Twenty patients with LELGC and 40 patients with non-LELGC were included in the training cohort. Significant differences were observed in Epstein–Barr virus (EBV) infection and vascular invasion between the two groups (p < 0.05). Significant differences were observed in the distribution of location, enhancement pattern, homogeneous enhancement, CT-defined lymph node status, and attenuations in the non-contrast, arterial, and venous phases (all p < 0.05). Enhancement pattern, CT-defined lymph node status, and attenuation in venous phase were independent predictors of LELGC. The optimal cutoff score of distinguishing LELGC from non-LELGC was 3.5. The area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy of risk identification model in the training cohort were 0.904, 87.5%, 80.0%, and 85.0%, respectively. The area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy of risk identification model in the validation cohort were 0.705 (95% CI 0.434–0.957), 75.0%, 63.6%, and 66.7%, respectively. Conclusion A preoperative risk identification model based on CT imaging data could be helpful for distinguishing LELGC from non-LELGC.
Collapse
Affiliation(s)
- Liming Li
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Gastrointestinal Tract, Henan Key Laboratory of Imaging Diagnosis and Treatment for Digestive System Tumor, Henan, China
| | - Wenpeng Huang
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Gastrointestinal Tract, Henan Key Laboratory of Imaging Diagnosis and Treatment for Digestive System Tumor, Henan, China
| | - Ping Hou
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Weiwei Li
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Menyun Feng
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yiyang Liu
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jianbo Gao
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Gastrointestinal Tract, Henan Key Laboratory of Imaging Diagnosis and Treatment for Digestive System Tumor, Henan, China
- *Correspondence: Jianbo Gao,
| |
Collapse
|
|
17
|
Yu HY, Li CP, Huang YH, Hsu SJ, Wang YP, Hsieh YC, Fang WL, Huang KH, Li AFY, Lee RC, Lee KL, Wu YH, Lai IC, Yang WC, Hung YP, Wang YC, Chen SH, Chen MH, Chao Y. Microsatellite Instability, Epstein-Barr Virus, and Programmed Cell Death Ligand 1 as Predictive Markers for Immunotherapy in Gastric Cancer. Cancers (Basel) 2022; 14:218. [PMID: 35008382 PMCID: PMC8750088 DOI: 10.3390/cancers14010218] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 12/28/2021] [Accepted: 12/30/2021] [Indexed: 12/17/2022] Open
Abstract
Immunotherapy benefits selected cases of gastric cancer (GC), but the correlation between biomarkers and prognosis is still unclear. Fifty-two patients with GC who underwent immunotherapy were enrolled from June 2016 to December 2020. Their clinical features and biomarkers-microsatellite instability-high (MSI-H), programmed cell death ligand 1 (PD-L1) combined positive score (CPS), and Epstein-Barr encoding region (EBER)-were analyzed. Eight patients had MSI-H, five patients had EBER, 29 patients had CPS ≥ 1, and 20 patients had no biomarker. The overall response rates (ORRs) of the MSI-H, EBER, PD-L1 CPS ≥ 1, and all-negative group were 75%, 60%, 44.8%, and 15%, respectively. Compared with that of the all-negative group, progression-free survival (PFS) was better in the MSI-H (p = 0.018), CPS ≥ 5 (p = 0.012), and CPS ≥ 10 (p = 0.006) groups, but not in the EBER (p = 0.2) and CPS ≥ 1 groups (p = 0.35). Ten patients had combined biomarkers, CPS ≥ 1 with either MSI-H or EBER. The ORRs were 66.7% for CPS ≥ 1 and MSI-H and 75% for CPS ≥ 1 and EBER. PFS was better in patients with combined biomarkers (p = 0.01). MSI-H, EBER, and CPS are useful biomarkers for predicting the efficacy of immunotherapy.
Collapse
Affiliation(s)
- Hung-Yuan Yu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112201, Taiwan; (H.-Y.Y.); (C.-P.L.); (Y.-H.H.); (S.-J.H.); (Y.-P.W.); (Y.-C.H.)
- Hospitalist Ward, Department of Medicine, Taipei Veterans General Hospital, Taipei 112201, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
| | - Chung-Pin Li
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112201, Taiwan; (H.-Y.Y.); (C.-P.L.); (Y.-H.H.); (S.-J.H.); (Y.-P.W.); (Y.-C.H.)
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
- Division of Clinical Skills Training, Department of Medical Education, Taipei Veterans General Hospital, Taipei 112201, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112201, Taiwan; (H.-Y.Y.); (C.-P.L.); (Y.-H.H.); (S.-J.H.); (Y.-P.W.); (Y.-C.H.)
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
| | - Shao-Jung Hsu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112201, Taiwan; (H.-Y.Y.); (C.-P.L.); (Y.-H.H.); (S.-J.H.); (Y.-P.W.); (Y.-C.H.)
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
| | - Yen-Po Wang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112201, Taiwan; (H.-Y.Y.); (C.-P.L.); (Y.-H.H.); (S.-J.H.); (Y.-P.W.); (Y.-C.H.)
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
| | - Yun-Cheng Hsieh
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112201, Taiwan; (H.-Y.Y.); (C.-P.L.); (Y.-H.H.); (S.-J.H.); (Y.-P.W.); (Y.-C.H.)
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
| | - Wen-Liang Fang
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 112201, Taiwan
| | - Kuo-Hung Huang
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 112201, Taiwan
| | - Anna Fen-Yau Li
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
- Department of Pathology, Taipei Veterans General Hospital, Taipei 112201, Taiwan
| | - Rheun-Chuan Lee
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
- Department of Radiology, Taipei Veterans General Hospital, Taipei 112201, Taiwan
| | - Kang-Lung Lee
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
- Department of Radiology, Taipei Veterans General Hospital, Taipei 112201, Taiwan
| | - Yuan-Hung Wu
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
- Department of Oncology, Taipei Veterans General Hospital, Taipei 112201, Taiwan
| | - I-Chun Lai
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
- Department of Oncology, Taipei Veterans General Hospital, Taipei 112201, Taiwan
| | - Wan-Chin Yang
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
- Department of Oncology, Taipei Veterans General Hospital, Taipei 112201, Taiwan
| | - Yi-Ping Hung
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
- Department of Oncology, Taipei Veterans General Hospital, Taipei 112201, Taiwan
| | - Yu-Chao Wang
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan;
| | - Shu-Hui Chen
- Department of Nursing, Taipei Veterans General Hospital, Taipei 112201, Taiwan;
| | - Ming-Huang Chen
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
- Department of Oncology, Taipei Veterans General Hospital, Taipei 112201, Taiwan
| | - Yee Chao
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan; (W.-L.F.); (K.-H.H.); (A.F.-Y.L.); (R.-C.L.); (K.-L.L.); (Y.-H.W.); (I.-C.L.); (W.-C.Y.); (Y.-P.H.)
- Department of Oncology, Taipei Veterans General Hospital, Taipei 112201, Taiwan
| |
Collapse
|
|
18
|
Yang W, Chen S, Cheng X, Xu B, Zeng H, Zou J, Su C, Chen Z. Characteristics of genomic mutations and signaling pathway alterations in thymic epithelial tumors. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1659. [PMID: 34988168 PMCID: PMC8667121 DOI: 10.21037/atm-21-5182] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 11/03/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND To elucidate the mechanisms of thymic epithelial tumor (TET) canceration by characterizing genomic mutations and signaling pathway alterations. METHODS Primary tumor and blood samples were collected from 21 patients diagnosed with TETs (thymoma and thymic cancer), 15 of whom were screened by nucleic acid extraction and whole exon sequencing. Bioinformatics was used to comprehensively analyze the sequencing data for these samples, including gene mutation information and the difference of tumor mutation burden (TMB) between thymoma and thymic carcinoma groups. We performed signaling pathway and functional enrichment analysis using the WebGestalt 2017 toolkit. RESULTS ZNF429 (36%) was the gene with the highest mutation frequency in thymic carcinoma. Mutations in BAP1 (14%), ABI1 (7%), BCL9L (7%), and CHEK2 (7%) were exclusively detected in thymic carcinoma, whereas ZNF721 mutations (14%) and PABPC1 (14%) were found exclusively in thymoma. The mean TMB values for thymic carcinoma and thymoma were 0.722 and 0.663 mutations per megabase (Mb), respectively, and these differences were not statistically significant. The ErbB signaling pathway was enriched in the thymoma and intersection groups, and pathways of central carbon metabolism in cancer, longevity regulating and MAPK signaling were only found in the thymoma group, while pathways in cancer (hsa05200) was found in the thymoma and thymic carcinoma groups. CONCLUSIONS Multiple differences in somatic genes and pathways have been identified. Our findings provide insights into differences between thymoma and thymic carcinoma that could aid in designing personalized clinical therapeutic strategies.
Collapse
Affiliation(s)
- Weilin Yang
- Department of Cardiothoracic Surgery of East Division, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Sai Chen
- Center for Private Medical Service & Healthcare, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xinxin Cheng
- Department of Cardiothoracic Surgery of East Division, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Bo Xu
- Department of Cardiothoracic Surgery of East Division, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huilan Zeng
- Department of Cardiothoracic Surgery of East Division, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jianyong Zou
- Department of Thoracic Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Chunhua Su
- Department of Thoracic Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhenguang Chen
- Department of Cardiothoracic Surgery of East Division, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.,Department of Thoracic Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| |
Collapse
|
|
19
|
Xie T, Peng Z, Liu Y, Zhang Z, Zhang X, Li J, Lu M, Gong J, Qi C, Ji J, Shen L. Clinicopathological Characteristics and Response to Chemotherapy in Treatment-Naive Epstein-Barr Virus Associated Gastric Cancer: A Retrospective Study. Front Oncol 2021; 11:611676. [PMID: 34631508 PMCID: PMC8495155 DOI: 10.3389/fonc.2021.611676] [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] [Received: 09/29/2020] [Accepted: 08/31/2021] [Indexed: 01/08/2023] Open
Abstract
Background Epstein–Barr virus associated gastric cancer (EBVaGC) is a special subtype of gastric cancer. However, the perioperative treatment plan and the response to chemotherapy are still uncertain. Methods We retrospectively enrolled patients diagnosed with EBVaGC from March 2013 to July 2020 in Beijing Cancer Hospital. Clinicopathological characteristics were recorded. Disease-free survival (DFS) were then calculated, and variants affecting DFS were tested in a Cox proportional regression model. Results One hundred sixty consecutive patients were finally included in our study. Of the patients, 96.9% had adenocarcinoma, while five had squamous cell carcinoma component. Most (70.9%) of them were poorly differentiated. Prevalent programmed death-ligand 1 (PD-L1) (69%) and minor HER-2 (3.8%) expression were noticed; all of the patients were MMR proficient (pMMR) or microsatellite stable (MSS). Among 33 patients who experienced neoadjuvant therapy, the number of tumor regression grade (TRG) 1, TRG 2, and TRG 3 was 5, 16, and 12, respectively. Patients with advanced tumor stage and T stage showed poorer response. Thirty-one patients experienced first-line chemotherapy; ORR was 33.3%, and DCR was 61.9%. One hundred forty-seven patients underwent surgery, and 27 of them showed disease recurrence; the 3-year DFS rate was 71.0%. Tumor stage, neoadjuvant chemotherapy, vascular invasion, and negative PD-L1 expression were associated with poorer DFS. Vascular invasion was the independent risk factor of DFS. Only seven patients reached OS with median follow-up time of 14 months. Conclusion EBVaGC exhibits unique clinicopathological characteristics. Neoadjuvant chemotherapy may not be suitable for EBVaGC, and EBVaGC exhibited relatively poor response to chemotherapy.
Collapse
Affiliation(s)
- Tong Xie
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Zhi Peng
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Yiqiang Liu
- Department of Pathology , Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Zhening Zhang
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiaotian Zhang
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Jian Li
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Ming Lu
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Jifang Gong
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Changsong Qi
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Jiafu Ji
- Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Lin Shen
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| |
Collapse
|
|
20
|
Ishikawa E, Satou A, Nakamura M, Nakamura S, Fujishiro M. Epstein-Barr Virus Positive B-Cell Lymphoproliferative Disorder of the Gastrointestinal Tract. Cancers (Basel) 2021; 13:3815. [PMID: 34359715 PMCID: PMC8345108 DOI: 10.3390/cancers13153815] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 07/23/2021] [Accepted: 07/25/2021] [Indexed: 12/12/2022] Open
Abstract
Epstein-Barr virus positive B-cell lymphoproliferative disorder (EBV+ B-LPD) encompasses a broad clinicopathological spectrum and distinct clinical behavior that relatively favors the gastrointestinal (GI) tract. In this review, we provide an update on the clinicopathological features and biological behavior of EBV-positive mucocutaneous ulcer (EBVMCU) and primary EBV+ diffuse large B-cell lymphoma (DLBCL) of the GI tract. EBVMCU is a newly recognized entity but well known as an indolent and self-limited EBV+ B-LPD occurring in various immunodeficiencies. In contrast, EBV+ DLBCL constitutes the largest group of EBV+ B-LPDs and is regarded as an aggressive neoplasm. These two distinct diseases have historically been distinguished in the reappraisal of age-related EBV-associated B-LPDs but are challenging in routine practice regarding their differential diagnostic and therapeutic approaches. An increasing number of reports indicate that they are epidemiologically prevalent beyond western and eastern countries, but their comprehensive analysis is still limited. We also describe the PD-L1 positivity of tumorous large cells and non-malignant immune cells, which is relevant for the prognostic delineation among patients with primary DLBCL of the GI tract with and without EBV on tumor cells.
Collapse
Affiliation(s)
- Eri Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan; (M.N.); (M.F.)
| | - Akira Satou
- Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute 480-1195, Japan;
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan; (M.N.); (M.F.)
| | - Shigeo Nakamura
- Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya 466-8550, Japan;
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan; (M.N.); (M.F.)
| |
Collapse
|
|
21
|
de Fátima Aquino Moreira-Nunes C, de Souza Almeida Titan Martins CN, Feio D, Lima IK, Lamarão LM, de Souza CRT, Costa IB, da Silva Maués JH, Soares PC, de Assumpção PP, Burbano RMR. PD-L1 Expression Associated with Epstein-Barr Virus Status and Patients' Survival in a Large Cohort of Gastric Cancer Patients in Northern Brazil. Cancers (Basel) 2021; 13:3107. [PMID: 34206307 PMCID: PMC8268941 DOI: 10.3390/cancers13133107] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 05/31/2021] [Accepted: 06/03/2021] [Indexed: 12/15/2022] Open
Abstract
Gastric cancer (GC) is a worldwide health problem, making it one of the most common types of cancer, in fifth place of all tumor types, and the third highest cause of cancer deaths in the world. There is a subgroup of GC that consists of tumors infected with the Epstein-Barr virus (EBV) and is characterized mainly by the overexpression of programmed cell death protein-ligand-1 (PD-L1). In the present study, we present histopathological and survival data of a thousand GC patients, associated with EBV status and PD-L1 expression. Of the thousand tumors analyzed, 190 were EBV-positive and the vast majority (86.8%) had a high relative expression of mRNA and PD-L1 protein (p < 0.0001) in relation to non-neoplastic control. On the other hand, in EBV-negative samples, the majority had a low PD-L1 expression of RNA and protein (p < 0.0001). In the Kaplan-Meier analysis, the probability of survival and increased overall survival of EBV-positive GC patients was impacted by the PD-L1 overexpression (p < 0.0001 and p = 0.004, respectively). However, the PD-L1 low expression was correlated with low overall survival in those patients. Patients with GC positive for EBV, presenting PD-L1 overexpression can benefit from immunotherapy treatments and performing the quantification of PD-L1 in gastric neoplasms should be adopted as routine.
Collapse
Affiliation(s)
- Caroline de Fátima Aquino Moreira-Nunes
- Laboratory of Molecular Biology, Department of Clinical Medicine, Ophir Loyola Hospital, Belém, 66063-240 PA, Brazil; (C.N.d.S.A.T.M.); (D.F.); (I.K.L.); (P.C.S.)
- Laboratory of Pharmacogenetics, Department of Medicine, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, 60430-275 CE, Brazil
| | | | - Danielle Feio
- Laboratory of Molecular Biology, Department of Clinical Medicine, Ophir Loyola Hospital, Belém, 66063-240 PA, Brazil; (C.N.d.S.A.T.M.); (D.F.); (I.K.L.); (P.C.S.)
| | - Isamu Komatsu Lima
- Laboratory of Molecular Biology, Department of Clinical Medicine, Ophir Loyola Hospital, Belém, 66063-240 PA, Brazil; (C.N.d.S.A.T.M.); (D.F.); (I.K.L.); (P.C.S.)
| | - Leticia Martins Lamarão
- Foundation Center for Hemotherapy and Hematology of Pará (HEMOPA), Department of Sorology, Belém, 66033-000 PA, Brazil;
| | | | - Igor Brasil Costa
- Department of Virology, Evandro Chagas Institute, Ananindeua, 67030-000 PA, Brazil;
| | - Jersey Heitor da Silva Maués
- Hematology and Transfusion Medicine Center, Laboratory of Molecular and Cell Biology, Department of Medicine, University of Campinas, Campinas, 13083-970 SP, Brazil;
| | - Paulo Cardoso Soares
- Laboratory of Molecular Biology, Department of Clinical Medicine, Ophir Loyola Hospital, Belém, 66063-240 PA, Brazil; (C.N.d.S.A.T.M.); (D.F.); (I.K.L.); (P.C.S.)
| | - Paulo Pimentel de Assumpção
- Oncology Research Center, Department of Biological Sciences, Federal University of Pará, Belém, 66073-005 PA, Brazil;
| | - Rommel Mário Rodríguez Burbano
- Laboratory of Molecular Biology, Department of Clinical Medicine, Ophir Loyola Hospital, Belém, 66063-240 PA, Brazil; (C.N.d.S.A.T.M.); (D.F.); (I.K.L.); (P.C.S.)
- Oncology Research Center, Department of Biological Sciences, Federal University of Pará, Belém, 66073-005 PA, Brazil;
| |
Collapse
|
|
22
|
Wei XL, Liu QW, Liu FR, Yuan SS, Li XF, Li JN, Yang AL, Ling YH. The clinicopathological significance and predictive value for immunotherapy of programmed death ligand-1 expression in Epstein-Barr virus-associated gastric cancer. Oncoimmunology 2021; 10:1938381. [PMID: 34235004 PMCID: PMC8216206 DOI: 10.1080/2162402x.2021.1938381] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
The effect of anti-programmed cell death 1 (PD-1) antibody in Epstein-Barr virus-associated gastric cancer (EBVaGC) was debatable, and no predictive biomarkers for efficacy have been reported. Public reports on anti-PD-1 antibody monotherapy-treated EBVaGC with available programmed death ligand-1 (PD-L1) expression status were summarized and analyzed. Relevance with clinicopathologic characteristics of PD-L1 expression by immunohistochemistry was analyzed in 159 patients diagnosed with EBVaGC. Relevance with genomic transcriptome and mutation profile of PD-L1 status in EBVaGC was assessed with three datasets, the cancer genome atlas (TCGA), Gene Expression Omnibus (GEO) GSE51575, and GSE62254. Based on the data from 8 reports, patients with positive PD-L1 expression (n = 30) had significantly superior objective response rate (ORR) than patients with negative PD-L1 expression (n = 9) (63.3% vs. 0%, P = .001) in EBVaGC receiving anti-PD-1 antibody monotherapy. PD-L1 positivity was associated with less aggressive clinicopathological characteristics and was an independent predictor for a longer disease-free survival (hazard ratio [HR] and 95% CI: 0.45 [0.22–0.92], P = .03) and overall survival (HR and 95% CI: 0.17 [0.06–0.43], P < .001). Analysis of public EBVaGC transcriptome and mutation datasets revealed enhanced immune-related signal pathways in PD-L1high EBVaGC and distinct mutation patterns in PD-L1low EBVaGC. PD-L1 positivity indicates a subtype of EBVaGC with ‘hot’ immune microenvironment, lower aggressiveness, better prognosis, and higher sensitivity to anti-PD-1 immunotherapy.
Collapse
Affiliation(s)
- Xiao-Li Wei
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Qian-Wen Liu
- Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Fu-Rong Liu
- Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Sha-Sha Yuan
- Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xiao-Fen Li
- Department of Abdominal Oncology, West China Hospital of Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Jia-Ning Li
- Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - An-Li Yang
- Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Yi-Hong Ling
- Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| |
Collapse
|
|
23
|
Zheng Z, Yin J, Liu XY, Yan XS, Xu R, Li MY, Cai J, Chen GY, Zhang J, Zhang ZT. Current indications for endoscopic submucosal dissection of early gastric cancer. World J Gastrointest Oncol 2021; 13:560-573. [PMID: 34163573 PMCID: PMC8204359 DOI: 10.4251/wjgo.v13.i6.560] [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: 02/05/2021] [Revised: 03/31/2021] [Accepted: 05/22/2021] [Indexed: 02/06/2023] Open
Abstract
The development of endoscopic treatment technology has further promoted the minimally invasive treatment of early gastric cancer (EGC). Endoscopic treatment has achieved better therapeutic effects in terms of safety and prognosis and is the preferred treatment method for patients who meet the indications for endoscopic treatment. However, the consequent problem is that some patients receiving endoscopic treatment may undergo non-curative resection, and the principle of follow-up management for non-curative resection patients deserves further attention. In addition, there are still debates on how to improve the accuracy of clinical staging, select a reasonable treatment method for patients who meet the expanded indications for endoscopic treatment, manage patients with positive endoscopic surgical margins, conduct research on function-preserving surgery, and manage the treatment of EGC under the current situation in China. Consequently, we aim to review current indications for endoscopic submucosal dissection of EGC in order to better inform treatment options.
Collapse
Affiliation(s)
- Zhi Zheng
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Jie Yin
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Xiao-Ye Liu
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Xiao-Sheng Yan
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Rui Xu
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Meng-Yi Li
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Jun Cai
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Guang-Yong Chen
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Jun Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Zhong-Tao Zhang
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| |
Collapse
|
|
24
|
Qi WX, Zhao S, Chen J. Epidemiology and prognosis of lymphoepithelioma-like carcinoma: a comprehensive analysis of surveillance, epidemiology, and end results (SEER) database. Int J Clin Oncol 2021; 26:1203-1211. [PMID: 33844112 DOI: 10.1007/s10147-021-01921-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 04/03/2021] [Indexed: 11/25/2022]
Abstract
AIM Lymphoepithelioma-like carcinoma (LELC) is a rare histological types of solid tumors. The present study aims to comprehensively describe the demographic and clinical features of LELC using surveillance, epidemiology, and end results (SEER) database, with an emphasis on the prognostic difference according to primary tumor sites of LELC. MATERIALS AND METHODS A population cohort with histologically diagnosed LELC were identified from SEER database between 1973 and 2016. Age-adjusted incidence rates and cancer-specific survival (CSS) were determined. Cox-regression proportional hazards model was used for both univariate and multivariate analyses. RESULTS In total, 2106 patients with LELC were identified, with the most common diagnosed primary tumor site of nasopharyngeal LELC (56.22%), followed by non-nasopharyngeal head and neck LELC (21.32%) and respiratory system (7.83%). The overall age-adjusted incidence of LELC was 0.091 per 100,000. The CSS rates of LELC patients at 5, 10, 15, and 20 years were 76%, 69%, 65%, and 61%, respectively. A tendency of decreasing incidence of LELC was observed in the past decade. Univariate analysis indicated that sex [hazard ratio (HR) 1.21, p = 0.031], year of diagnosis (HR 0.60 and 0.63, p < 0.001), race (HR 1.29, p = 0.0021), age (HR 1.25, p = 0.0072), summary tumor stage (HR 1.97, and 4.57, both p < 0.001), number of positive LN(HR2.21, p < 0.001), surgery (HR 0.58, p = 0.0033), chemotherapy (HR 1.19, p = 0.037) and primary tumor site (p < 0.001) were significant factors associated with prognosis of LELC. In multivariate analysis, age (HR 1.75, p = 0.03), distant stage (HR 6.57, p = 0.0001), number of positive LN (HR 2.63, p = 0.0015) and non-nasopharyngeal head and neck LELC (HR 0.37, p = 0.0031) were significantly independent predictors for CSS of LELC. In sub-group analysis, radiotherapy significantly improves CSS for nasopharyngeal LELC (HR 0.57, p = 0.0002), while surgery significantly improve CSS for non-nasopharyngeal LELC (HR 0.33, p < 0.0001). CONCLUSION Based on SEER data analysis, age older than 50 years, distant stage and more than three positive LN are significantly associated with worse CSS for LELC, while the prognosis of non-nasopharyngeal head and neck LELC is significantly better than nasopharyngeal LELC. Local treatments for LELC could be recommended according to primary tumor sites.
Collapse
Affiliation(s)
- Wei-Xiang Qi
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Shengguang Zhao
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
| | - Jiayi Chen
- Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
| |
Collapse
|
|
25
|
Pyo JS, Kim NY, Kang DW. Clinicopathological Significance of EBV-Infected Gastric Carcinomas: A Meta-Analysis. ACTA ACUST UNITED AC 2020; 56:medicina56070345. [PMID: 32668573 PMCID: PMC7404405 DOI: 10.3390/medicina56070345] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 07/02/2020] [Accepted: 07/09/2020] [Indexed: 02/06/2023]
Abstract
Background and objectives: The present study aims to elucidate the clinicopathologic significance of Epstein-Barr virus (EBV) infection in gastric carcinomas (GCs) through a meta-analysis. Materials and Methods: Sixty-one eligible studies were included in the present meta-analysis. The included patients, with and without EBV infection, were 2063 and 17,684, respectively. We investigated the clinicopathologic characteristics and various biomarkers, including programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs). Results: The estimated EBV-infected rate of GCs was 0.113 (95% confidence interval (CI): 0.088-0.143). The EBV infection rates in GC cells were 0.138 (95% CI: 0.096-0.194), 0.103 (95% CI: 0.077-0.137), 0.080 (95% CI: 0.061-0.106), and 0.042 (95% CI: 0.016-0.106) in the population of Asia, America, Europe, and Africa, respectively. There was a significant difference between EBV-infected and noninfected GCs in the male: female ratio, but not other clinicopathological characteristics. EBV infection rates were higher in GC with lymphoid stroma (0.573, 95% CI: 0.428-0.706) than other histologic types of GCs. There were significant differences in high AT-rich interactive domain-containing protein 1A (ARID1A) and PD-L1 expressions, and high CD8+ TILs between EBV-infected and noninfected GCs. Conclusions: Our results showed that EBV infection of GCs was frequently found in male patients and GCs with lymphoid stroma. EBV infection was significantly correlated with ARID1A and PD-L1 expressions and CD8+ TILs in GCs.
Collapse
Affiliation(s)
- Jung-Soo Pyo
- Department of Pathology, Daejeon Eulji University Hospital, Eulji University School of Medicine, Daejeon 35233, Korea;
| | - Nae-Yu Kim
- Department of Internal Medicine, Daejeon Eulji University Hospital, Eulji University School of Medicine, Daejeon 35233, Korea;
| | - Dong-Wook Kang
- Department of Pathology, Chungnam National University Sejong Hospital, 20 Bodeum 7-ro, Sejong 30099, Korea
- Department of Pathology, Chungnam National University School of Medicine, 266 Munhwa Street, Daejeon 35015, Korea
- Correspondence: ; Tel.: +82-10-8561-9895
| |
Collapse
|