Low rate of apoptosis and overexpression of bcl-2 in Epstein-Barr virus-associated gastric carcinoma

Aims: Epstein-Barr virus (EBV) has been demonstrated in about 10% of gastric carcinomas. However, the pathogenetic role of EBV in gastric carcinoma is uncertain. We compared the rate of apoptotic cell death, cell proliferation and the expression of apoptosis-related proteins in gastric carcinomas with or without EBV. Methods and results: Epstein-Barr virus was detected in 40 gastric carcinomas by EBV-encoded small RNA-1 insitu hybridization. Apoptotic cell death, MIB-1, p53, bcl-2 and bcl-x were examined by the terminal deoxynucleotidyl-mediated dUTP-nick end labelling method and immunohistochemistry. We also included 40 age-, sex- and disease stage-matched EBV-negative cases as a control. The number of apoptotic cells was significantly lower in EBV-positive (20+/-15,1/1000 cells) and bcl-2-positive (17+/-12.9/1000 cells) tumours than in EBV-negative (43+/-37.1) and bcl-2-negative tumours (38+/-32.1, P<0.001, P<0.001, respectively), bcl-2 immunostaining was significantly higher in EBV-positive tumours (24 cases) than in EBV-negative tumours (12 cases, P<0.05), There was no significant difference in bcl-x and p53 expression between EBV-positive and -negative tumours, The number of MIB-1-positive cells in EBV-positive tumours (237+/-161/1000) was significantly lower than in EBV-negative tumours (480+/-208/1000 cells, P<0.001), Conclusions: A low rate of apoptosis and high bcl-2 expression were recognized in EBV-positive gastric carcinomas, suggesting that bcl-2 protein is the main inhibitor of apoptosis in EBV-positive carcinomas. In addition, the low apoptotic and proliferative activities may reflect a low biological activity in EBV-positive gastric carcinomas.