Apoptosis And Expression Of Bcl-2 In Epstein-Barr Virus-Associated Gastric Carcinoma

Objective EBV has been found in most cases of rare gastric lymphoepithelioma-like carcinoma and a small but significant proportion of common gastric adenocarcinoma. EBV DNA could be detected in about 7-10% gastric adenocarcinomas. However, the pathoge-netic role of EBV in gastric carcinoma is uncertain. In order to explore the potential pathogenic role of EBV-encoded proteins and bcl-2 protein in the oncogenic pathway, we detected the expression of some EBV-encoded proteins in EBV-associated gastric carcinoma (EBVaGC), compared the rate of apoptotic cells and the expression of bcl-2 protein in EB-VaGC and clinicopathological data matched EBV-negative gastric carcinoma (EBVnGC).Methods The apoptotic index(AI) and the expression of bcl-2 protein were tested by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labelling (TUNED and immunohistochemistry respectively in 13 EBVaGCs and 45 EBVnGCs. The expression of related genes of EBV was tested by RT-PCR and Southern blotting.Results (1)AI of EBVaGCs, EBVnGCs and the corresponding adjacent tissues of EBVaGCs were 0. 9692 +0. 4131,2. 0333 +0. 6000 and 3. 2538 +0. 4594 respectively. AI of EBVaGC was significantly lower than that of EBVnGC(t=5. 9795, P=0) and corresponding adjacent tissues of EBVaGC(t=13. 2229, P=0). (2)The number of apoptotic cells was significantly lower in bcl-2-postive(l. 5793+0. 6946)tumours than bcl-2-negative tumours (2. 0103+0. 6842,P<0. 05). (3)The expression of bcl-2 protein was detectded in 29 of 58 (50. 00%) gastric carcinomas and in 17(29. 31%) of 58 adjacent tissues. There was significant difference between the two groups(x2 =4. 3214, P=0. 0376). The expression of bcl-2 protein was detectded in 7 of 13(53. 85%) EBVaGCs and in 22 of 45 (48. 89%) EBVnGCs. The difference between the two groups was not significant (x2 = 0. 0991, P = 0. 7529). (4) EBNA1 mRNA was detected in all of 13 EBVaGCs, while both EBNA2 and LMP1 mRNA were not detected in 13 cases. Of the 13 EBV-positive samples, 6 exhibited BARF1 transcripts and 2 exhibited BHRF1 transcripts.Conclusions (1) bcl-2 expression did not correlate with the presence of EBV in EBVaGC. (2)Significant low rate of apoptosis in EBVaGC suggested that EBV infection could inhibit cell apoptosis. However, the mechanism by which EBV inhibit cell apoptosis did not induce bcl-2 expression. (3)No expression of EBNA2 and LMP1 proteins in EBVaGCsuggested that EBNA2 and LMP1 did not correlate with the cell apoptosis and bcl-2 expression. Early genes BARFl and BHRFl might play an important role in the development and progression of gastric carcinomas by the mechanisms of immortalizing epithelial cells and inhibiting cell apoptosis.