Interrelationship between Epstein-Barr virus infection in gastric carcinomas and the expression of apoptosis-associated proteins.
OBJECTIVE
Epstein-Barr virus (EBV) and its associated proteins may be protective against the occurrence of apoptosis that would normally inhibit cancer development and progression. Alternatively, the viral infection may cause altered or mutated expression of oncogenes or tumour suppressor genes that are necessary for tumour development, an action that may also involve apoptosis. In this study, a relationship was sought between occurrence of EBV infection, expression of apoptosis-associated proteins (tumour suppressor gene p53 and oncogenes c-myc and bcl-2) and levels of cell death (apoptosis or necrosis) in 119 cases of gastric carcinoma.


RESULTS
The EBV status of the gastric carcinomas (using the EBV-encoded small RNA I (EBER-1) and in-situ hybridization), stage and grade of tumour and sex of patients were compared for bcl-2, p53 and c-myc expression patterns. EBER-1 was detected in approximately 20% of cases studied. There was no significant correlation between levels of cell death in the tumour tissue and EBV status. In the protein analyses, development and progression of gastric carcinoma, with or without EBV infection, was independent of bcl-2 expression. However, in gastric cancers with EBV infection, p53 overexpression was inhibited and c-myc expression was increased in early stage cancers, in comparison with decreased c-myc expression in late stage cancers.


CONCLUSIONS
The p53 and c-myc expression patterns indicate that EBV-infected gastric carcinomas are less likely to have a natural regression via apoptosis at an early stage and explain, in part, the resistance to treatment of late stage of gastric cancers.
Ishii
H
H
Second Department of Pathology, Tokyo Medical University, Japan. hhishii@tokyo-med.ac.jp
Gobé
G
G
Kawakubo
Y
Y
Sato
Y
Y
Ebihara
Y
Y
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020031:Epstein-Barr Virus Infections / Q000378:metabolism* / Q000473:pathology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D004268:DNA-Binding Proteins; C099537:Epstein-Barr virus encoded RNA 1; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D012334:RNA, Neoplasm; D012367:RNA, Viral; D016159:Tumor Suppressor Protein p53