title: Expression of c-myc and PCNA in Epstein-Barr virus-associated gastric carcinoma.
abstract: The aim of this study was to detect the expression of proliferatng cell nuclear antigen (PCNA) and c-myc in Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC), as well as the expression of EBV-encoded proteins in EBVaGC and their effect on carcinogenesis and the development of gastric cancer. The PCNA and c-myc protein levels were assessed by immunohistochemistry in 13 EBVaGC and 45 EBVnGC specimens. The expression of related genes of EBV, including EB nuclear antigen (NA)-1 and EBNA2 genes, latent membrane protein 1 (LMP1) and early genes BARF1 and BHRF1 were tested by reverse transcription-polymerase chain reaction (RT-PCR) and southern blotting. The PCNA labeling index (LI) of EBVaGCs, EBVnGCs and the corresponding adjacent tissues of EBVaGCs were 49.3768±12.1832, 14.839±7.1847, 35.613±8.3831 and 24.2735±10.1332, respectively. The PCNA LI was significantly different between EBVaGC and EBVnGC of EBVaGC (t=4.686, P<0.01). The difference between EBVaGC and corresponding adjacent tissues of EBVaGC was also significant (t=8.805, P<0.01). The expression of c-myc protein was detected in 33 of 58 (55.39%) gastric carcinomas and in 21 of 58 (36.21%) adjacent tissues. There was a significant difference between the two groups (χ2=4.989, P<0.05). The expression of the c-myc protein was detected in 8 of 13 (61.54%) EBVaGCs and in 25 of 45 (55.56%) EBVnGCs. The difference between the two groups was not significant (χ2=0.147, P>0.05). EBNA1 mRNA was detected in all 13 EBVaGC cases, while EBNA2 and LMP1 mRNA was not detected in these cases. Of the 13 EBV-positive samples, 6 exhibited BARF1 transcripts and 2 exhibited BHRF1 transcripts. c-myc expression did not correlate with the presence of EBV in EBVaGC. EBV infection may induce PCNA expression. The lack of EBNA2 and LMP1 protein expression in EBVaGC suggests that EBNA2 and LMP1 do not correlate with cell apoptosis and c-myc expression. Early genes BARF1 and BHRF1 may play an important role in the development and progression of gastric carcinomas by immortalizing epithelial cells.
authors.affiliation: Department of Oncology, Yantai Yuhuangding Hospital, Yantai, Shandong 264000;
authors.forename: Shiguang
authors.initials: S
authors.lastname: Zhu
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Liping
authors.initials: L
authors.lastname: Yan
authors.forename: Bing
authors.initials: B
authors.lastname: Luo
keywords: Epstein-Barr virus; c-myc; immunohistochemistry; progressive genes; proliferating cell nuclear antigen; reverse transcription-polymerase chain reaction; stomach neoplasm