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Epstein-Barr virus associated gastric carcinoma

About: Epstein-Barr virus associated gastric carcinoma is a research topic. Over the lifetime, 132 publications have been published within this topic receiving 17400 citations.


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Journal ArticleDOI
Adam J. Bass1, Vesteinn Thorsson2, Ilya Shmulevich2, Sheila Reynolds2  +254 moreInstitutions (32)
11 Sep 2014-Nature
TL;DR: A comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project is described and a molecular classification dividing gastric cancer into four subtypes is proposed.
Abstract: Gastric cancer was the world’s third leading cause of cancer mortality in 2012, responsible for 723,000 deaths1. The vast majority of gastric cancers are adenocarcinomas, which can be further subdivided into intestinal and diffuse types according to the Lauren classification2. An alternative system, proposed by the World Health Organization, divides gastric cancer into papillary, tubular, mucinous (colloid) and poorly cohesive carcinomas3. These classification systems have little clinical utility, making the development of robust classifiers that can guide patient therapy an urgent priority. The majority of gastric cancers are associated with infectious agents, including the bacterium Helicobacter pylori4 and Epstein–Barr virus (EBV). The distribution of histological subtypes of gastric cancer and the frequencies of H. pylori and EBV associated gastric cancer vary across the globe5. A small minority of gastric cancer cases are associated with germline mutation in E-cadherin (CDH1)6 or mismatch repair genes7 (Lynch syndrome), whereas sporadic mismatch repair-deficient gastric cancers have epigenetic silencing of MLH1 in the context of a CpG island methylator phenotype (CIMP)8. Molecular profiling of gastric cancer has been performed using gene expression or DNA sequencing9–12, but has not led to a clear biologic classification scheme. The goals of this study by The Cancer Genome Atlas (TCGA) were to develop a robust molecular classification of gastric cancer and to identify dysregulated pathways and candidate drivers of distinct classes of gastric cancer.

4,583 citations

Journal Article
TL;DR: The authors investigated the possibility that EBV may be present not only in the rare gastric cancers that resemble nasopharyngeal lymphoepithelioma, but also in typical gastric adenocarcinoma, and found some cases of gastric carcinoma are EBV-associated.
Abstract: The Epstein-Barr virus (EBV) has been detected in certain types of lymphoma and some epithelial neoplasms including nasopharyngeal lymphoepithelioma, and rare lymphoepithelioma-like carcinomas occurring in a variety of organs including, most recently, the stomach. The authors investigated the possibility that EBV may be present not only in the rare gastric cancers that resemble nasopharyngeal lymphoepithelioma, but also in typical gastric adenocarcinoma. EBV sequences were detected in 22 of 138 (16%) cases of typical gastric adenocarcinoma by polymerase chain reaction and in situ hybridization (ISH) techniques. The EBV genomes were specifically present within the gastric carcinoma cells in an even distribution. The EBV genomes were also present in adjacent dysplastic epithelium but were absent in surrounding lymphocytes, other normal stromal cells, intestinal metaplasia, and normal gastric mucosa. The EBV genomes in the infected gastric carcinoma cells are expressed as EBV RNA was detected by ISH. EBV was most often detected in gastric tumors from men (21%) compared with women (3%). Thus some cases of gastric adenocarcinoma are EBV-associated.

581 citations

Journal ArticleDOI
TL;DR: Findings strongly suggest a causal relation between a significant proportion of gastric carcinoma and EBV, and the virus-carrying carcinoma cells may evade immune surveillance.
Abstract: In 1000 primary gastric carcinomas, 70 (7.0%) contained Epstein-Barr virus (EBV) genomic sequences detected by PCR and Southern blots. The positive tumors comprised 8 of 9 (89%) undifferentiated lymphoepithelioma-like carcinomas, 27 of 476 (5.7%) poorly differentiated adenocarcinomas, and 35 of 515 (6.8%) moderately to well-differentiated adenocarcinomas. In situ EBV-encoded small RNA 1 hybridization and hematoxylin/eosin staining in adjacent sections showed that the EBV was present in every carcinoma cell but was not significantly present in lymphoid stroma and in normal mucosa. Two-color immunofluorescence and hematoxylin/eosin staining in parallel sections revealed that every keratin-positive epithelial malignant cell expressed EBV-determined nuclear antigen 1 (EBNA1) but did not significantly express CD45+ infiltrating leukocytes. A single fused terminal fragment was detected in each of the EBNA1-expressing tumors, thereby suggesting that the EBV-carrying gastric carcinomas represent clonal proliferation of cells infected with EBV. The carcinoma cells had exclusively EBNA1 but not EBNA2, -3A, -3B, and -3C; leader protein; and latent membrane protein 1 because of methylation. The patients with EBV-carrying gastric carcinoma had elevated serum EBV-specific antibodies. The EBV-specific cellular immunity was not significantly reduced; however, the cytotoxic T-cell target antigens were not expressed. These findings strongly suggest a causal relation between a significant proportion of gastric carcinoma and EBV, and the virus-carrying carcinoma cells may evade immune surveillance.

450 citations

Journal ArticleDOI
TL;DR: EBV-positive gastric cancers greatly differ from other gastric carcinomas based on sex, anatomic subsite, and surgically disrupted anatomy, indicating that it is a distinct etiologic entity.

385 citations

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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20216
20205
20196
20184
20174
20164