Epstein-Barr virus-associated gastric carcinoma: a newly defined entity.

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a recently recognized entity, which is defined by the presence of EBV in the gastric carcinoma cells. EBVaGC represents about 10% of gastric carcinoma worldwide, and >80,000 patients are estimated to develop EBVaGC annually. EBVaGC shows some distinct clinicopathologic characteristics, such as male predominance, predisposition to the proximal stomach, and a high proportion in diffuse-type gastric carcinomas. Besides, EBVaGC also shows characteristic molecular abnormality, that is, global and nonrandom CpG-island methylation of the promoter region of many cancer-related genes, which causes downregulation of their expression. Moreover, EBVaGC has a relative favorable prognosis. The uniform presence of EBV-encoded small RNA in tumor cells but not in the surrounding normal epithelial cells, and the detection of monoclonal EBV episomes in EBVaGC, strongly suggests that EBV play an etiological role in gastric carcinogenesis. Therefore, EBVaGC should be regarded as a distinct entity of gastric carcinoma, although it only accounts for a relatively small fraction of total gastric carcinomas. In this review, the epidemiological and clinicopathologic features of EBVaGC and the genetic abnormalities of EBVaGC cell including chromosomal and epigenetic abnormalities are described. The roles of EBV in gastric carcinogenesis are discussed. We make an emphasis on the EBV latency pattern and genome polymorphisms as well as local immunity in EBVaGC. In addition, the treatment of EBVaGC is also briefly discussed. Taken together, this review aims to give the reader a full understanding of a newly defined entity of gastric carcinoma, EBVaGC.