The Overexpression Of P53 Protein In Epstein-Barr Virus-Associated Gastric Carcinoma

Objective To understand the expression of p53 protein in EBV-associated gastric car-cinomas(EBVaGC) and EBV-negative gastric carcinomas(EBVnGC) with matched clinico-pathological data,and to investigate the role of EBV infection and the expression of p53 protein in the genesis and development of gastric carcinoma.Methods 185 gastric carcinoma tissues and 185 corresponding adjacent tissues of gastric carcinoma were tested for EBV DNA genome by polymerase chain reaction (PCR)-Southern blotting. The presence of EBV was further confirmed by in situ hybridization (ISH) in paraffin-embedded sections for EBV-encoded small RNA (EBERs) among the positive samples of PCR. 13 EBVaGC, 45 EBVnGC with matched clinicopathological data and 58 corresponding adjacent tissues of gastric carcinoma were tested for the expression of p53 protein by immunohistochemical method. The related genes of EBV were tested by RT-PCR.Results (1) EBERs was detected in 13 (7. 03%) of the 185 gastric carcinoma tissues, but absent in the corresponding adjacent tissues of gastric carcinoma. The difference of the EBV positivity was significant between carcinoma and adjacent tissues (X2= 11. 0709, P = 0. 0009). (2) p53 immunoreactivity was detected in 50 of 58 gastric carcinomas and absent in the 58 corresponding adjacent tissues. There were significant difference between the two groups (P=0. 0000). (3) The expression of p53 protein was detected in 39 of 45 EBVnGC (86. 7%) and 11 of 13 EBVaGC (84. 6%) respectively. The overexpression of p53 protein was demonstrated in only 2 of 13 EBVaGC (15. 4%). This was in marked contrast to the frequency of 57. 8% (26/45) in EBVnGC (P = 0. 0085). But the expression of p53 in EBVaGC and EBVnGC was similar (P=0. 7912). (4) The transcripts of EBNA1 was detected in all of 13 EBVaGC,BZLF1 was detected in 6 of 13 EBVaGC (46. 2%), but no LMP1 transcripts was detected in 13 cases.Conclusion (1) The expression of p53 protein is related with the genesis of gastric carcinoma. (2) The infection of EBV in gastric carcinoma tissues is related with the abnormal expression of p53 protein. EBV-encoded proteins can interact with p53 gene or p53 protein in different ways, and may play different roles in the genesis or development ofEBVaGC. (3) EBERs signals were restricted to a localized area of the tumour in one cases of EBVaGC, which could have been secondarily infection. (4) The weak to moderate p53 protein expression in EBVaGC is suggestive of a non-mutational mechanism. While the homogeneous intense staining of most tumour nuclei in EBVnGC perhaps represents muta-tional mechanism of p53 gene.