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


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.
Zur Hausen
A
A
Department of Pathology, Vrije Universiteit Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
van Rees
B P
BP
van Beek
J
J
Craanen
M E
ME
Bloemena
E
E
Offerhaus
G J A
GJ
Meijer
C J L M
CJ
van den Brule
A J C
AJ
D000230:Adenocarcinoma / Q000473:pathology / Q000821:virology*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D018450:Disease Progression; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000032:analysis; D005260:Female; D018530:Gastric Stump; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008679:Metaplasia / Q000821:virology; D011230:Precancerous Conditions / Q000821:virology; D012367:RNA, Viral / Q000032:analysis; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000473:pathology / Q000821:virology*
D019309:Epstein-Barr Virus Nuclear Antigens; C099537:Epstein-Barr virus encoded RNA 1; C106732:Epstein-Barr virus encoded RNA 2; D012367:RNA, Viral; C417029:EBV-encoded nuclear antigen 1