Role and prognostic significance of proapoptotic proteins in Epstein-Barr virus-infected gastric carcinomas.
BACKGROUND
The purposes of the present study were to evaluate the role and the prognostic values of proapoptotic proteins involved in the death receptors (Fas and TRAIL receptors) and mitochondrial pathways (Bax) in Epstein-Barr virus (EBV)-infected gastric carcinomas.


METHODS
Fifty-five EBV-infected gastric carcinomas were identified by in situ hybridization for EBV-encoded small RNAs. Immunohistochemistry was performed for Fas, Fas-ligand, FADD, TRAIL, DR4, DR5 and Bax. Apoptotic indices (AIs) were determined using TUNEL assay and assessed.


RESULTS
No remarkable differences in protein expressions were observed between EBV-infected gastric carcinomas and conventional gastric carcinomas. Bax positivity tended to be associated with higher AI (p = 0.068), whereas Fas and FADD positivities were related to lower AI (p = 0.006 and 0.059, respectively). Proteins involved in TRAIL pathways showed no statistical significant relationship with AI. TNM stage and Fas and FADD expressions were related to overall survival (p < 0.05), but TNM stage was the only independent prognostic factor.


CONCLUSIONS
Apoptosis in EBV-infected gastric carcinomas probably occurs via the mitochondrial pathway through Bax, rather than via the death receptor pathways. Fas and FADD expressions, and pathological tumor stage (TNM stage) may be the prognostic factors.
Chang
Mee Soo
MS
Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Seoul 110-799, South Korea.
Lee
Hye Seung
HS
Jung
Eun Ji
EJ
Kim
Chul Woo
CW
Lee
Byung Lan
BL
Kim
Woo Ho
WH
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D015996:Survival Rate; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; D053222:Fas Ligand Protein; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D051028:bcl-2-Associated X Protein