EPSTEIN-BARR VIRUS-ASSOCIATED GASTRIC-CARCINOMA AND EPSTEIN-BARR-VIRUS INFECTION OF THE STOMACH

BACKGROUND: Epstein-Barr virus (EBV) has been found to be associated w ith a type of gastric carcinoma (EBVaGC). However, many questions rema in unanswered, such as epidemiology, and pathologic features of EBVaGC and the significance of EBV in the genesis of EBVaGC. EXPERIMENTAL DE SIGN: Gastric carcinoma and non-neoplastic mucosa were evaluated to re veal the following issues: the incidence of EBVaGC in Japanese populat ion, pathologic features and EBV genotype, clonality, and gene-express ion in EBVaGC, localization of EBV in nonneoplastic stomach, and serum titer of anti-EBV antibodies in EBVaGC-carrying patients. RESULTS: Us ing PCR and EBER1 in situ hybridization, EBVaGC (definitely amplifiabl e EBV-DNA and positive EBER1-signal in the nuclei of carcinoma cells) was found in 8 of 72 gastric carcinomas (11%). The dominant genotype o f EBV was type A (7/8), with type C (6/8), and F (8/8) restriction enz yme polymorphism, which are the predominant type of EBV found in throa t washing of the general population in Japan. EBVaGC was found in the cardia (4/8) or body (4/8) of the stomach, and consisted of 7 advanced and 1 intramucosal carcinoma. By Southern blot analysis of EBVaGC hyb ridized with right- and left-side probe adjacent to the terminal repea ts, EBV was present in a monoclonal episomal form in all of the EBVaGC . EBVaGC lacked expression of EBNA2 (0/8) and LMP1 (0/8) by immunocyto chemistry. In non-neoplastic mucosa, EBER1 signal was identified in th e infiltrating lymphocytes and shedding epithelial cells predominantly in fundic gland mucosa of patients with EBVaGC (8/8). Patients with E BVaGC showed high titers of anti-VCA IgG (8/8), anti-VCA IgA (2/8) and anti-EA IgG (7/8) antibodies just before surgery. CONCLUSIONS: EBV ma y infect the surface epithelium of the stomach through the reactivated EBV-carrying lymphocytes. EBV may be a factor initiating EBVaGC, Anti -EBV antibodies or EBER1 in situ hybridization may help to identify pa tients at high risk for EBVaGC.