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.

MATERIALS AND 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.

CONCLUSION

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.