EBV Encoded RNA 양성 위암에서 EBV Latent Membrane Protein 1 유전자 변화와 TGF-β1, TGF-βRII, p21,p16, E2F1, Thymidylate Synthase 및 NF-κB 단백 발현에 대한 면역조직화학적 연구

Abstract

Background : Although clinicopathologic differences have been described between Epstein- Barr virus (EBV)-positive and negative gastric adenocarcinomas, the pathogenetic basis for these differences remains unclear. In this study, efforts were made to confirm that expression of EBV-latent membrane protein (LMP1) and immunohistochemical characteristics of EBVpositive gastric adenocarcinomas. Methods : We investigated genomic deletion, and RNA & protein expression of the EBV-LMP1, as well as immunohistochemical protein expression of transforming growth factor (TGF)-β1, TGF-βRII, p21, p16, E2F1, thymidylate synthase, and NF-κB in relation to EBV positive gastric adenocarcinoma. Results : A total of 38 Epstein-Barr Virus Encoded RNA-positive and 80 negative gastric carcinomas were examined. A 30 bp DNA deletion in the EBV-LMP1 gene, initiating at codon 342, was detected in 94.4% of EBVpositive cases. By RT-PCR and western blotting, EBV-LMP1 mRNA and protein expressions were absent in all cases, re- gardless of DNA deletion. No significant differences in TGF-β1, TGF-βRII, p21, NF-κB, E2F1, or thymidylate synthase expression were identified. However, the decreased expression of p16 was found in 84.2% of EBV-positive carcinomas, relative to only 57.5% of EBV-negative tumors (p=0.024). Conclusion : EBV-LMP1 DNA deletion, mRNA and protein losses are highly prevalent in EBV-positive gastric adenocarcinoma among Korean patients, along with decreased p16 expression.