The comparison of the prognosis between Epstein-Barr virus (EBV)-positive gastric carcinomas and EBV-negative ones (original) (raw)

Characteristics of Epstein-Barr virus-associated gastric cancer: A study of 235 cases at a comprehensive cancer center in U.S.A

Journal of Experimental & Clinical Cancer Research, 2009

Background Epstein-Barr virus (EBV) has been shown to be associated with gastric cancer. However, inconsistent findings have been reported regarding the distribution of EBV infected cells (in normal gastric epithelium vs. intestinal metaplastic cells vs. in neoplastic cells) and the characteristics of EBV-associated gastric cancer. Lymph node positive EBV-associated gastric cancer has not been systematically studied. The aims of this study were to evaluate EBV-associated gastric cancer, to assess the distribution of EBV infected cells including all positive lymph nodes, and to define the characteristics of EBV-associated gastric cancer. Design The study included primary gastric cancer patients who underwent surgical resection with no preoperative treatment at M.D. Anderson Cancer Center between 1987 and 2006. Formalin-fixed paraffin-embedded tissue from these resection specimens were assessed for EBV by in situ hybridization, the gold standard for EBV detection in tissue. EBV status was analyzed along with clinicopathologic parameters including age, gender, tumor type, lymph node status, and pathologic stage of the tumor. Results Among 235 patients, 12 had intranuclear expression of EBV. EBV staining was seen only in tumor cells and no detectable EBV was observed in normal gastric mucosa, intestinal metaplasia or stromal cells. Eight of 12 patients with EBV-associated gastric cancer had regional lymph node metastasis. Of note, metastatic tumor cells in all of the involved lymph nodes of these 8 cases contained EBV. The epidemiologic data showed 11 of the 12 patients with EBV-associated gastric cancer were men, ranging in age from 54 to 78 years (mean age, 60 years; median age, 62.1 years). The age distribution for non-EBV associated gastric cancer patients ranged from 21 to 93 years (mean age, 67 years; median age, 66.4 years). Conclusion Our study demonstrated that EBV is present exclusively in gastric cancer cells. The detection of EBV in tumor cells in all of the lymph nodes involved with metastatic gastric carcinoma suggests simultaneous replication of EBV and tumor cells. The predominantly male gender and relatively younger age observed for the EBV-infected gastric cancer cases suggest an association between this disease and other factors, such as life style.

Epstein-Barr virus and gastric carcinoma in Western patients: comparison of pathological parameters and p53 expression in EBV-positive and negative tumours

Histopathology, 2000

Epstein±Barr virus and gastric carcinoma in Western patients: comparison of pathological parameters and p53 expression in EBV-positive and negative tumours PS100-positive dendritic cells and with HLA-DR expression by tumour cells (P 0.03). p53 immunoreactivity in more than 30% of tumour cells was detected in 25 out 49 EBV-negative cases and was absent in EBV-positive cases except in one case with focal EBER-positivity. Conclusions: Focal staining for EBER is an unusual ®nding in the setting of gastric carcinoma and these results suggest that there might be two types of EBVassociated gastric carcinoma in which the viral infection will play a different role. The presence of a stromal lymphoid reaction which is strongly correlated with EBV positivity, is associated with antigen-presenting ability by HLA-DR-positive tumour cells or abundant dendritic cells. The function of p53 appears preserved in all EBV-associated carcinomas except in one case with focal EBER expression whereas the immunohistochemical pattern of p53 is suggestive of a mutational phenomenon in 51% of EBV-negative cases.

Descriptive Study of Tumor Immune Microenvironment and Epstein-Barr Virus Infection in Gastric Adenocarcinoma

Acta Gastroenterológica Latinoamericana

Introduction. The Cauca region, in Colombia, has a high incidence of gastric cancer and there are few studies describing tumor microenvironment in gastric cancer samples obtained from this geographic region. Aim. The aim of this study was to describe the infiltration of CD3+, CD8+ T cells, the expression of programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1), and Epstein-Barr virus infection in biopsies from Cauca patients with advanced intestinal-type gastric adenocarcinoma. Methodology. This is a descriptive cross-sectional study of 24 gastrectomy samples out of 48 samples analyzed. Expression of CD3, CD8, PD-1, and PD-L1 was analyzed using immunohistochemistry, and infection by Epstein-Barr virus was analyzed by Epstein-Barr virus-encoded small RNA in-situ hybridization (EBER-ISH) in gastric tissue samples on formalin-fixed, paraffin-embedded. Finally, the immunoscore and the Combined Positive Score were calculated. Results. ITGA samples were 21.8% ± 13.6% and 14.8% ±...

Clinicopathological characteristics of Epstein-Barr virus-positive gastric cancer in Latvia

European Journal of Gastroenterology & Hepatology, 2019

Objective Epstein-Barr virus (EBV)-associated gastric cancer has been proposed to be a distinct gastric cancer molecular subtype. The prognostic significance of EBV infection in gastric cancer remains unclear and needs further investigation. Our study aimed to analyze EBV-positive and EBV-negative gastric cancer patients regarding their personal and tumor-related characteristics, and compare their overall survival. Methods Gastric cancer patients consecutively treated at the Riga East University Hospital during 2009-2016 were identified retrospectively. Tumor EBV status was determined by in-situ hybridization for EBV-encoded RNA (EBER). Information about clinicopathological characteristics was obtained from patient questionnaires, hospital records. Overall survival was ascertained through 30 July 2017. Cox proportional hazard regression models adjusted for personal and tumor-related covariates compared survival between EBV-positive and EBV-negative patients. Results There were a total of 302 gastric cancer patients (61% males) with mean and SD age 63.6 ± 11.5 years. EBER positivity was present in 8.6% of tumors. EBV-positive gastric cancer patients had better survival at 80 months [adjusted hazard ratio = 0.37, 95% confidence interval (CI) = 0.19-0.72] compared to EBV-negative patients. Worse survival was observed for patients with stage III (hazard ratio = 2.76, 95% CI = 1.67-4.56) and stage IV (hazard ratio = 10.02, 95% CI = 5.72-17.57) compared to stage I gastric cancer, and overlapping and unspecified subsite (hazard ratio = 1.85; 95% CI = 1.14; 3.00) compared to distal tumors. Conclusion Tumor EBV positivity is a favorable prognostic factor in gastric cancer.

Epstein-Barr virus is associated with gastric carcinoma: The question is what is the significance?

World Journal of Gastroenterology, 2008

To examine the possible role of the Epstein-Barr Virus (EBV) in the development of gastric adenocarcinoma (GC). It is unclear whether EBV is involved in GC development or is a consequence of gastric inflammation secondary to immunosuppressive treatments. METHODS: A systematic review was carried out of all published observational studies on the temporal association between EBV and GC, with a view to determine a causal relationship.

Improved survival of gastric cancer with tumour Epstein–Barr virus positivity: an international pooled analysis

Gut, 2013

Background and objective-About 9% of gastric carcinomas have Epstein-Barr virus (EBV) in the tumour cells, but it is unclear whether viral presence influences clinical progression. We therefore examined a large multicentre case series for the association of tumour EBV status with survival after gastric cancer diagnosis, accounting for surgical stage and other prognostic factors. Methods-We combined individual-level data on 4599 gastric cancer patients diagnosed between 1976 and 2010 from 13 studies in Asia (n=8), Europe (n=3), and Latin America (n=2). EBV positivity of tumours was assessed by in situ hybridisation. Mortality HRs for EBV positivity were estimated by Cox regression models stratified by study, adjusted for distributions of sex (71% male), age (mean 58 years), stage (52% tumour-node-metastasis stages III or IV), tumour histology (49% poorly differentiated, 57% Lauren intestinal-type), anatomic subsite (70% noncardia) and year of diagnosis. Variations by study and continent were assessed using studyspecific HRs for EBV positivity. Results-During median 3.0 years follow-up, 49% of patients died. Stage was strongly predictive of mortality, with unadjusted HRs (vs stage I) of 3.1 for stage II, 8.1 for stage III and 13.2 for stage IV. Tumour EBV positivity was 8.2% overall and inversely associated with stage (adjusted OR: 0.79 per unit change). Adjusted for stage and other confounders, EBV positivity was associated with lower mortality (HR, 0.72; 95% CI 0.61 to 0.86), with low heterogeneity among the study populations (p=0.2). The association did not significantly vary across patient or tumour characteristics. There was no significant variation among the three continent-specific HRs (p=0.4). Conclusions-Our findings suggest that tumour EBV positivity is an additional prognostic indicator in gastric cancer. Further studies are warranted to identify the mechanisms underlying this protective association. ‡ The intestinal-type included the Japanese classifications tubular, papillary and mucinous adenocarcinomas, and the diffuse-type included poorly differentiated adenocarcinoma, signet-ring cell carcinoma

Is Epstein - Barr virus Infection a Late Event in Gastric Tumour Pathogenesis or a True Aetiological Agent?

2009

Objectives. To determine the association of Epstein-Barr Virus in gastric tumours in the Kingdom of Bahrain and to explore its role in tumour pathogenesis. Method. A reterospective study was performed including 58 cases of gastric tumours between January 2001 till December 2005 received in Histopathology department Salmaniya Medical Complex, Kingdom of Bahrain. These cases consist of carcinomas, carcinoids and lymphomas. Formalin fixed tissue sections were used to perform immunohistochemistry and InSitu Hybridization using Anti-EBV-LMP (Latent Membrane Protein) antibodies and EBER PNA probe respectively. Results.- The EBV-RNA expression was detected in 44.40% of the intestinal type adenocarcinomas, 25% signet ring cell type adenocarcinomas, 100% carcinoid tumours and 50% lymphomas (p value < 0.036). Tumours showing positive staining pattern for EBER PNA probe were also positive for EBV-LMP except the carcinoid tumours. Of the EBV positive carcinoma cases 75% were poorly different...

Epstein-Barr virus is absent in gastric superficial neoplastic lesions

Virchows Archiv, 2019

Epstein-Barr virus (EBV) has been associated with about 9% of all gastric carcinomas, but its role in gastric carcinogenesis remains unclear since there is lack of evidence of EBV presence in pre-neoplastic lesions of gastric mucosa. This study intends to determine the prevalence of EBV in gastric dysplasia and superficial neoplasia to clarify whether EBV infection is an early or late event in gastric cancer development. This retrospective study included a total of 242 gastric lesions from 199 consecutive patients who were referred for endoscopic resection. The histological classification of lesions includes 137 low-and high-grade dysplasia and 105 superficial carcinomas. EBV infection was investigated by EBER-ISH. Results showed that EBV was not detected in any epithelial cells of any case with dysplasia or superficial carcinomas, although we observed the presence of a small number of EBV-infected lymphocytes in 2.1% of all lesions. These results showed that EBV is not present in gastric dysplasia neither in superficial carcinomas suggesting that EBV carcinogenesis is a late event in well/moderately differentiated gastric carcinogenesis.

Overview of Epstein–Barr-Virus-Associated Gastric Cancer Correlated with Prognostic Classification and Development of Therapeutic Options

International Journal of Molecular Sciences, 2020

Gastric cancer (GC) is a deadly disease with poor prognosis that is characterized by heterogeneity. New classifications based on histologic features, genotypes, and molecular phenotypes, for example, the Cancer Genome Atlas subtypes and those by the Asian Cancer Research Group, help understand the carcinogenic differences in GC and have led to the identification of an Epstein–Barr virus (EBV)-related GC subtype (EBVaGC), providing new indications for tailored treatment and prognostic factors. This article provides a review of the features of EBVaGC and an update on the latest insights from EBV-related research with a particular focus on the strict interaction between EBV infection and the gastric tumor environment, including the host immune response. This information may help increase our knowledge of EBVaGC pathogenesis and the mechanisms that sustain the immune response of patients since this mechanism has been demonstrated to offer a survival advantage in a proportion of patients...