Epstein-Barr virus and aberrant expression of mdm2 and p53 in pathogenesis and development of gastric carcinoma

Abstract

AIM: To investigate the role of p53 and mdm2 gene abnormality in oncogenesis and development of Epstein-Barr virus (EBV) -associated gastric carcinoma (EBVaGC) and to explore the relationship between EBV infection and P53 and mdm2 protein expression. METHODS: p53 gene mutation in exon 5-8 was detected by polymerase chain reaction and single strand conformation polymorphism analysis (PCR-SSCP), and DNA sequencing. p53 and mdm2 protein expression was tested by immunohistochemistry in EBVaGCs (n=13), EBVnGCs (EBV negative gastric carcinomas, n = 45) with matched clinicopathological parameters and corresponding adjacent tissues of gastric carcinoma (n=58). RESULTS: The positive rates of p53 and mdm2 protein in gastric carcinomas were significantly higher than those in corresponding adjacent normal tissues (86.2%, 29.3% vs 0%, 0% respectively; P0.01). There were no significant difference between the positive rates of p53 and mdm2 protein in EBVnGCs and EBVaGCs. The overexpression rate of p53 protein was 15.4% (2/13) in EBVaGCs. This was in marked contrast to the rate of 57.8% (26/45) in EBVnGCs (X2=7.2593, P=0.0 0850.01). There was significant positive correlation between mdm2 expression and p53 overexpression (X2 =11.1839, P= 0.0 0080.01, r= 0.4 391). p53 gene mutation was found in only 2 cases of EBVnGCs and both occurred at exon 5. No p53 gene mutation was detected in 13 cases of EBVaGCs and 58 corresponding adjacent tissues. CONCLUSION: Abnormal accumulation of p53 protein might not result from p53 gene mutation. mdm2 protein may play an important role in the pathogenesis of gastric carcinoma through suppressing the function of wild type p53 protein. The infection of EBV relates to the abnomal expression of p53 protein, but not to the abnomal expression of mdm2 protein and p53 gene mutation in gastric carcinoma