Korean J Pathol.  2006 Jun;40(3):176-184.

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 Gastric Adenocarcinoma

Affiliations
  • 1Department of Pathology, Yonsei University, Wonju College of Medicine, Wonju, Korea. meeyon@ yonsei.ac.kr
  • 2Department of Surgery, Yonsei University, Wonju College of Medicine, Wonju, Korea.
  • 3Department of Microbiology, Yonsei University, Wonju College of Medicine, Wonju, Korea.

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.

Keyword

Stomach neoplasms; Epstein-Barr virus; EBV-Associated Membrane Antigen; Protein p16

MeSH Terms

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*
Codon
DNA
Membrane Proteins
NF-kappa B
RNA
RNA, Messenger
Thymidylate Synthase
Transforming Growth Factors
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