Epstein-Barr Virus (EBV)-associated gastric carcinoma

Abstract

The ubiquitous Epstein-Barr virus (EBV) is associated with several human tumors, which include lymphoid and epithelial malignancies. It is known that EBV persistently infects the memory B cell pool of healthy individuals by activating growth and survival signaling pathways that can contribute to B cell lymphomagenesis. Although the monoclonal proliferation of EBV-infected cells can be observed in epithelial tumors, such as nasopharyngeal carcinoma and EBV-associated gastric carcinoma, the precise role of EBV in the carcinogenic progress is not fully understood. This review features characteristics and current understanding of EBV-associated gastric carcinoma. EBV-associated gastric carcinoma comprises almost 10% of all gastric carcinoma cases and expresses restricted EBV latent genes (Latency I). Firstly, definition, epidemiology, and clinical features are discussed. Then, the route of infection and carcinogenic role of viral genes are presented. Of particular interest, the association with frequent genomic CpG methylation and role of miRNA for carcinogenesis are topically discussed. Finally, the possibility of therapies targeting EBV-associated gastric carcinoma is proposed.

Figure 1

Lymphoepithelioma-like subtype of Epstein-Barr virus-associated gastric carcinomas (EBVaGC). A. Hematoxylin-Eosin Staining. B.EBV-encoded small ribonucleic acid-in situ hybridization (EBER1-ISH) demonstrates positive nuclei in the carcinoma cells, which are surrounded by infiltrating lymphocytes.

Figure 2

Endoscopic image of an early EBVaGC in the upper gastric body. The tumor shows protruded shape probably because of the abundant lymphocyte infiltration.

Figure 3

Cell-to-cell contact-mediated EBV transmission to epithelial cells. In cell-free infection, EBV preferentially infects B cells using CD21 receptor. EBV also infects CD21-negative epithelial cells as part of its normal life cycle, however much less efficiently. EBV transfer mediated by cell-to-cell contact with B cells increases the infection efficiency 1,000 to 10,000-fold compared with cell-free virus infection.

Figure 4

EBVaGC by site in the stomach. A. Distribution of EBVaGC. EBV prevalence was more frequent in the cardia and middle stomach than in the antrum, where over half of EBV-negative gastric cancers were located. B. EBV involvement in remnant cancer by site. Note that frequency of EBV infection in the non remnant cardiac cancer was 10.5% [22].