Genetic Analysis of Epstein-Barr Virus Latent Membrane Protein 1 and Immunohistochemical Expression of Transforming Growth Factor (TGF)-beta1, TGF-betaRII, p21, p16, E2F1, Thymidylate Synthase, and NF-kappaB in Epstein-Barr Virus Encoded RNA-positive Gast.
- Author:
Mee Yon CHO
;
Minseob EOM
;
Kwang Hwa PARK
;
Mee Dong KIM
;
Seung Hoon SUNG
;
Myoung Soo KIM
;
Dae Sung KIM
;
Sun Ju CHOI
- Publication Type:Original Article
- Keywords:
Stomach neoplasms;
Epstein-Barr virus;
EBV-Associated Membrane Antigen;
Protein p16
- MeSH:
Adenocarcinoma*;
Blotting, Western;
Codon;
DNA;
Herpesvirus 4, Human*;
Humans;
Membrane Proteins*;
Membranes*;
NF-kappa B*;
RNA;
RNA, Messenger;
Stomach Neoplasms;
Thymidylate Synthase*;
Transforming Growth Factors*
- From:Korean Journal of Pathology
2006;40(3):176-184
- CountryRepublic of Korea
- Language:English
-
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)-beta1, TGF-bata RII, p21, p16, E2F1, thymidylate synthase, and NF-kappaB 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-bata1, TGF-betaRII, p21, NF-kappaB, 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.