Meta-analysis Shows That Prevalence of Epstein–Barr Virus-Positive Gastric Cancer Differs Based on Sex and Anatomic Location

Murphy, Gwen; Pfeiffer, Ruth M.; Camargo, M. Constanza; Rabkin, Charles S.

doi:10.1053/j.gastro.2009.05.001

Cited by 410 publications

(421 citation statements)

References 63 publications

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“…7 It has been suggested that the profound global DNA effects are responsible for the distinctive clinicopathologic features of EBV gastric cancers 20 including male predominance 9,30 and proximal location. 31 Notably, the purported younger age has not been confirmed by recent analysis. 19,32 In the current study, we confirmed the non-antral location.…”

Section: Discussionmentioning

confidence: 90%

A protein and mRNA expression-based classification of gastric cancer

et al. 2016

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The overall survival of gastric carcinoma patients remains poor despite improved control over known risk factors and surveillance. This highlights the need for new classifications, driven towards identification of potential therapeutic targets. Using sophisticated molecular technologies and analysis, three groups recently provided genetic and epigenetic molecular classifications of gastric cancer (The Cancer Genome Atlas, 'Singapore-Duke' study, and Asian Cancer Research Group). Suggested by these classifications, here, we examined the expression of 14 biomarkers in a cohort of 146 gastric adenocarcinomas and performed unsupervised hierarchical clustering analysis using less expensive and widely available immunohistochemistry and in situ hybridization. Ultimately, we identified five groups of gastric cancers based on Epstein-Barr virus (EBV) positivity, microsatellite instability, aberrant E-cadherin, and p53 expression; the remaining cases constituted a group characterized by normal p53 expression. In addition, the five categories correspond to the reported molecular subgroups by virtue of clinicopathologic features. Furthermore, evaluation between these clusters and survival using the Cox proportional hazards model showed a trend for superior survival in the EBV and microsatellite-instable related adenocarcinomas. In conclusion, we offer as a proposal a simplified algorithm that is able to reproduce the recently proposed molecular subgroups of gastric adenocarcinoma, using immunohistochemical and in situ hybridization techniques. Gastric carcinoma is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. Despite better control over known risk factors and development of new chemotherapeutic and targeted agents, in the United States, the 5-year overall survival for gastric cancer patients is only 29%. 1 With regard to patient stratification, although several morphologic classifications have been developed, one broadly used system is the Lauren classification, which divides gastric adenocarcinoma into intestinal and diffuse types. 2 The simple two-tiered classification gives a general understanding of the histogenesis and biology of gastric cancer, and has been particularly helpful in evaluating the epidemiologic data. Another widely used system is the WHO classification, which is based on more precise histologic patterns. It is an all-inclusive system, which recognizes all the rare subtypes that were not identified in the Lauren classification. 3 Nevertheless, its clinical utility is doubtful as there is little difference in outcomes between the distinct histological subgroups.Following the successful Trastuzumab for Gastric Cancer (ToGA) trial, the only validated predictive biomarker for personalized therapy of gastric cancer is limited to human epidermal growth factor receptor (Her2) protein expression. 4 Recently, anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibody (ramucirumab) has been FDA approved, and anti-epidermal growth factor receptor (EGFR) an...

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Section: Discussionmentioning

confidence: 90%

A protein and mRNA expression-based classification of gastric cancer

et al. 2016

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“…LELC constitutes only 1-4 % of all GCs [2][3][4] and has been described as having a favorable prognosis compared with that of ordinary GC, especially in LELCs with Epstein-Barr virus (EBV) infection [1,[5][6][7][8][9]. EBV infection is found in more than 80 % of LELC cases, and EBVpositive LELCs share the following features with EBVassociated GCs: male predominance, predisposition to the proximal part of the stomach, and a high proportion of diffuse-type gastric carcinomas [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr virus infection serves as an independent predictor of survival in patients with lymphoepithelioma-like gastric carcinoma

et al. 2015

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Background The pathogenesis and clinicopathologic characteristics of Epstein-Barr virus (EBV)-negative lymphoepithelioma-like gastric carcinoma (LELC) are still unclear. In addition, it remains controversial whether EBV infection itself affects the prognosis of LELC. Methods Between 1995 and 2011, 145 LELC patients (124 patients with EBV infection and 21 patients without EBV infection) underwent radical gastrectomy with D2 lymph node dissection. The clinicopathologic features and prognosis of EBV-negative LELC cases were compared with those of EBV-positive LELC cases. The median duration of follow-up after surgery was 55 months. Microsatellite instability (MSI) analysis was performed on 20 EBV-negative LELC cases. Results EBV-negative LELC accounted for 14.5 % of the total LELC cases. EBV-negative LELC was significantly associated with older age, female sex, advanced T stage, and advanced American Joint Committee on Cancer (AJCC) tumor stage compared with EBV-positive LELC. In univariate analysis, patients with EBV-negative LELC had significantly shorter overall, disease-specific, and recurrencefree survival than those with EBV-positive LELC. The 5-year overall survival rates were 81.0 % for patients with EBVnegative LELC and 96.2 % for patients with EBV-positive LELC. In a Cox proportional hazards model, EBV infection, age, and AJCC tumor stage were identified as independent predictors of overall survival. MSI-high, MSI-low, and microsatellite-stable tumors accounted for 25, 10, and 65 % of EBV-negative LELC cases, respectively. MSI status did not affect the prognosis of EBV-negative LELC cases. Conclusions EBV infection serves as an independent predictor of survival in patients with LELC. EBV-negative LELC exhibited clinicopathologic features and prognosis distinct from those of EBV-positive LELC.

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“…However, the Prevalence rates of EBV in gastroesophageal cancer vary between 5 and 20%, which may depend on the patient groups in different studies [16][17][18]. EBV-associated tumori-genesis appears to be rather restricted to gastric cancer while the role of EBV in other parts such as esophageal carcinomas appears to be insignificant in most parts of the globe [19]. To the best of our knowledge there no study investigated the role of the EBV in the etiology of EC from Sudan.…”

Section: Discussionmentioning

confidence: 85%

Esophageal Cancer in the Sudan: Focus on the Screening for EBV and the Surgical Management

Ahmed

Beely

Aziz

et al. 2017

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Objective: The aim of this study was to screen for the existence of Epstein Barr Virus (EBV) in esophageal cancer (EC) tissue samples obtained from Sudanese patients and to review the available literature associated with surgical management. Methodology:In this retrospective study 102 formalin fixed paraffin wax embedded tissue's blocks were retrieved from histopathology laboratories in Khartoum City, Sudan and subsequently tested by Immunohistochemical methods for the presence of EBV. All specimens were previously diagnosed as having esophageal carcinoma. Results:As regards Immuno histochemistry (IHC) staining for EBV, positive findings were revealed in 22 (21.5%) and 79/ (78.5%) of the study subjects were negative. Of the 55 males with esophageal cancer, 15/55 (27%) were identified with EBV infection and the remaining 40/55(73%) found without EBV infection. Of the 46 females with esophageal cancer, 7/46(13%) were found positive for EBV immuno staining and the remaining 39/46(87 %) were found negative for EBV. Conclusion:EBV might have some etiological effects contributing to the occurrence of esophageal cancer in Sudan. Crucial preventive strategies are extremely needed to reduce the burden of esophageal cancer in Sudan.

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Meta-analysis Shows That Prevalence of Epstein–Barr Virus-Positive Gastric Cancer Differs Based on Sex and Anatomic Location

Cited by 410 publications

References 63 publications

A protein and mRNA expression-based classification of gastric cancer

A protein and mRNA expression-based classification of gastric cancer

Epstein-Barr virus infection serves as an independent predictor of survival in patients with lymphoepithelioma-like gastric carcinoma

Esophageal Cancer in the Sudan: Focus on the Screening for EBV and the Surgical Management

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