Epstein-Barr virus and gastric carcinoma.

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC), which accounts for most lymphoepithelioma-like gastric carcinoma and 10% or less of ordinary gastric carcinoma, is found worldwide and is the most common EBV-associated neoplasm. The pathologic features of EBVaGC are male predominance, occurrence primarily in the proximal stomach, multiplicity, moderately or poorly differentiated histological type, and association with lymphocytic infiltration. Virologically, EBV in EBVaGC is monoclonal or oligoclonal in the intramucosal or early invasive stage, and invariably monoclonal in advanced carcinomas. Latency type of gene expression in EBV is the same as that in Burkitt lymphoma (latency type I). Thus, EBVaGC is a unique type of gastric carcinoma, which is derived from a single or a few EBV-infected epithelial cells. However, there are still some unanswered questions, such as the mechanism of EBV infection of epithelial cells, the primary target in the gastric epithelium, the molecular events underlying EBVaGC, and the interaction of EBV with cytokine genes in cancer cells, as well as the predisposing factors for EBVaGC. To develop an experimental model, we recently established a transplantable EBVaGC - in severe combined immunodeficiency (SCID) mice - which retains the original EBV and the same pattern of latency gene expression as the original carcinoma. The development of a new therapeutic approach using this model, such as a gene therapy specific to EBV-associated neoplasm, will make EBVaGC not only a pathologically but also a clinically distinct gastric carcinoma entity.