Abstract
OBJECTIVE: The expression of B-cell lymphoma 2 (Bcl-2) seems to be influenced by the endocrine environment. Numerous reports demonstrate the diverse expression of Bcl-2 family members under sex steroid regulation. With the exception of estrogen-related tumors, androgen-related tumors have shown their characteristics in Bcl-2 expression. In this study, the status of Bcl-2 expression in male hepatocellular carcinoma (HCC) patients was examined to verify the high incidence of HCC in males. METHODS: Tumor tissue microarray was used to examine Bcl-2 expression levels in 374 HCC cases including 306 males and 68 females. Kaplan-Meier method, log-rank test, and Cox proportional hazards model were applied to investigate the predictive value of Bcl-2 in HCC patients. RESULTS: Immunohistochemistry analysis showed that male patients with higher Bcl-2 levels had significantly longer median survival time and recurrence time than those with lower levels. However, no significant differences in outcomes were found between different Bcl-2 levels in female patients. When the male patients were stratified into several age points, the level of Bcl-2 expression showed poorer predictive efficiency in the 45-49 and 55-60 age groups in andropause-age patients compared with other age groups. Bcl-2 was an independent prognostic factor for both overall survival (P < 0.0001) and recurrence time (P = 0.0001) in male patients. After excluding male patients in the 45-60 age group, the predictive efficiency was enhanced (n = 147, OS, P = 0.0002, TTR, P < 0.0001). CONCLUSIONS: Bcl-2 expression is an independent predictor of survival and recurrence in male HCC. Bcl-2 levels may also be regulated by androgens or androgen receptors in male HCC patients. Bcl-2 levels change and exhibit poor predictive efficiency when androgen levels vary dramatically (andropause age).