A Study Of Epstein-Barr Virus-Associated Gastric Carcinoma And Mdm2, P53 And P21 Gene Abnormality

Objective To understand p53 gene mutation the expression of mdm2, p53 and p21 protein in EBV-associated gastric carcinoma (EBVaGC) , EBV-negative gastric carcinoma (EBVnGC) with matched clinicopathological parameters and corresponding adjacent tissues of gastric carcinoma. To analyse the potential pathogenic role of EBV infection and mdm2,p53 and p21 gene abnormality in the development of gastric carcinoma.Methods p53 gene mutation in exon 5~8 was tested by PCR-SSCP assay. mdm2,p53 and p21 protein expression were tested by the immunohistochemistry in 13 EBVaGCs, 45 EBVnGCs with matched clinicopathological parameters and 58 corresponding adjacent tissues of gastric carcinoma .Results (1) The expression of p53 protein was detected in 39 of 45 EBVnGCs (86. 67%) and 11 of 13 EBVaGCs(84. 62%) respectively. The overexpression of p53 protein was demonstrated in only 2 of 13 EBVaGCs(15. 38%). This was in marked contrast to the frequency of 57. 78%(26/45)in EBVnGC (P = 0. 0085). But the expression of p53 in EBVaGC and EBVnGC was similar(P=0. 7912). (2) p21 immunoreactivity was detected in 36 of 58 gastric carcinomas and 52 of 58 corresponding adjacent normal tissues. There were significant difference between the two groups(x2 = 12. 5, P = 0. 0004). The expression of p21 protein was detected in 26 of 45 EBVnGCs(57. 78%) and 10 of 13 EBVaGCs (76. 92%) respectively. The expression of p21 in EBVaGC and EBVnGC was similar(P= 0. 3531). (3) mdm2 immunoreactivity was detected in 17 of 58 gastric carcinomas and absent in 58 corresponding adjacent normal tissues. There were significant difference between the two groups (x2 = 15. 059,P=0. 0001). The expression of mdm2 protein was detected in 14 of 45 EBVnGCs(31.11%) and 3 of 13 EBVaGCs(23. 08%) respectively. The expression of mdm2 in EBVaGC and EBVnGC was similar(x2 =0. 04609,P=0. 8300). (4) There was significant correlation between mdm2 expression and p53 overexpression (x2 = 11. 1839,P=0. 0008,r=0. 4391) ,but there was no significant correlation between p21 and p53 expression(x2 = 1. 3228,P = 0. 2501,r=0. 2025). (5)p53 gene mutation was found in only 2 cases of EBVnGCs and both were exon 5. No p53 gene mutation was detected in 13 EBVaGCs and 58 corresponding adjacent tissues.Conclusion (1) The abnomal expression of mdm2,p53 and p21 protein is related withthe oncogenesis of gastric carcinoma. (2) p53 protein expression and overexpression are common in gastric carcinoma,but p53 protein abnormal accumulation might not result from p53 gene mutation. (3) There is no relation between the infection of EBV and the abnomal expression of mdm2 and p21 proteins in gastric carcinoma tissues . (4) The co-expression positive rate of p21 and p53 was high, but there was no significant correlation between p21 and p53 expression, suggesting that expression of p21 protein was induced by p53-depend-ent pathway as well as p53-independent pathway. (5) The rate of p53 protein overexpression in EBVaGCs was much lower than that in EBVnGCs. The rate of p21 protein expression in EBVaGCs was higher than that in EBVnGCs,but there was no significant difference between them. This suggest that the function of wild-p53 were suppressed by EBV. ㏕he expression of mdm2 was significantly associated with high levels of p53 protein, suggesting that mdm2 protein may play an important role in the pathogenesis of gastric carcinoma through suppressing the function of wide type p53 protein.