Low rate of apoptosis and overexpression of bcl-2 in Epstein-Barr virus-associated gastric carcinoma.
OBJECTIVE
Epstein-Barr virus (EBV) has been demonstrated in about 10% of gastric carcinomas. However, the pathogenetic role of EBV in gastric carcinoma is uncertain. We compared the rate of apoptotic cell death, cell proliferation and the expression of apoptosis-related proteins in gastric carcinomas with or without EBV.


RESULTS
Epstein-Barr virus was detected in 40 gastric carcinomas by EBV-encoded small RNA-1 in-situ hybridization. Apoptotic cell death, MIB-1, p53, bcl-2 and bcl-x were examined by the terminal deoxynucleotidyl-mediated dUTP-nick end labelling method and immunohistochemistry. We also included 40 age-, sex- and disease stage-matched EBV-negative cases as a control. The number of apoptotic cells was significantly lower in EBV-positive (20 +/- 15. 1/1000 cells) and bcl-2-positive (17 +/- 12.9/1000 cells) tumours than in EBV-negative (43 +/- 37.1) and bcl-2-negative tumours (38 +/- 32.1, P < 0.001, P < 0.001, respectively). bcl-2 immunostaining was significantly higher in EBV-positive tumours (24 cases) than in EBV-negative tumours (12 cases, P < 0.05). There was no significant difference in bcl-x and p53 expression between EBV-positive and -negative tumours. The number of MIB-1-positive cells in EBV-positive tumours (237 +/- 161/1000) was significantly lower than in EBV-negative tumours (480 +/- 208/1000 cells, P < 0.001).


CONCLUSIONS
A low rate of apoptosis and high bcl-2 expression were recognized in EBV-positive gastric carcinomas, suggesting that bcl-2 protein is the main inhibitor of apoptosis in EBV-positive carcinomas. In addition, the low apoptotic and proliferative activities may reflect a low biological activity in EBV-positive gastric carcinomas.
Kume
T
T
First Department of Pathology, School of Medicine, Fukuoka University, Fukuoka, Japan.
Oshima
K
K
Shinohara
T
T
Takeo
H
H
Yamashita
Y
Y
Shirakusa
T
T
Kikuchi
M
M
D000328:Adult; D000368:Aged; D017209:Apoptosis; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D005260:Female; D006566:Herpesviridae Infections / Q000378:metabolism* / Q000473:pathology*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D014412:Tumor Virus Infections / Q000378:metabolism* / Q000473:pathology*
D019253:Proto-Oncogene Proteins c-bcl-2