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. 2004 May;57(5):487-91.
doi: 10.1136/jcp.2003.014068.

Epstein-Barr virus in gastric carcinomas and gastric stump carcinomas: a late event in gastric carcinogenesis

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Epstein-Barr virus in gastric carcinomas and gastric stump carcinomas: a late event in gastric carcinogenesis

A Zur Hausen et al. J Clin Pathol. 2004 May.

Abstract

Background: To determine at what stage during gastric carcinogenesis Epstein-Barr virus (EBV) enters the gastric epithelial cells, the presence of EBV was investigated in two pathogenetically related but distinct forms of adenocarcinoma of the stomach-gastric carcinoma of the intact stomach (GCIS) and gastric stump carcinoma (GSC)-and their presumed precursor lesions.

Patients and methods: Eleven patients with EBV positive GCIS and eight patients with EBV positive GSC, demonstrated by the highly sensitive EBV encoded RNA 1/2 (EBER1/2) RNA in situ hybridisation (RISH) technique, were studied. Paraffin wax embedded tissue available from preoperative gastric biopsies and tumour adjacent tissue from the resection specimens containing normal gastric mucosa, inflamed gastric mucosa, and preneoplastic lesions (intestinal metaplasia and dysplasia) was investigated by EBER1/2 RISH, in addition to EBV nuclear antigen 1 (EBNA-1) and latent membrane protein 1 (LMP-1) immunohistochemistry (IHC).

Results: In both GCIS and GSC and their precursor lesions EBER1/2 transcripts were restricted to the carcinoma cells. In addition, positivity of EBNA-1 IHC was also restricted to the tumour cells. IHC for LMP-1 was negative in all cases tested.

Conclusions: The absence of EBER1/2 transcripts in preneoplastic gastric lesions (intestinal metaplasia and dysplasia) and their presence in two distinct types of gastric carcinoma strongly suggest that EBV can only infect neoplastic gastric cells and thus is a late event in gastric carcinogenesis.

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Figures

Figure 1
Figure 1
(A) Epstein-Barr virus (EBV) encoded RNA 1/2 (EBER1/2) RNA in situ hybridisation in a gastric carcinoma of the intact stomach revealing specific EBER1/2 transcripts (dark) in the nuclei of the tumour cells. A corresponding slide shows (B) tumour cells with specific nuclear expression of EBV nuclear antigen 1 (dark brown), whereas (C) staining for latent membrane protein 1 is negative. (D) Expression of CD21 (brown) is restricted to dendritic cells, whereas the overlying gastric epithelium is negative.
Figure 2
Figure 2
(A) Epstein-Barr virus (EBV) encoded RNA 1/2 (EBER1/2) positive tumour cells (dark brown) of a gastric stump carcinoma (GSC) adjacent to EBER1/2 negative gastric epithelium with intestinal metaplasia. (B) EBER1/2 positive tumour cells (dark brown) of a GSC adjacent to EBER1/2 negative overlying gastric epithelium

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