Hepatocellular carcinoma and markers of apoptosis (bcl-2, bax, bcl-x): Prognostic significance

Patients with tumors expressing promoters of apoptosis (bax) versus inhibitors of apoptosis (bcl-2, bcl-x) may have increased survival. The purpose of this study was to determine the frequency of expression of apoptotic markers in hepatocellular carcinoma (HCC) and their relationship with prognosis. Seventy HCC were immunostained for bcl-2, bax, and bcl-x. Staining intensity in tumor cells was graded 0 to 3+. Follow-up data were available for mean survival (57 cases) and death rates (58 cases). These values and clinical parameters were related to prognosis. Staining frequency for bcl-2, bax, and bcl-x was 20%, 66%, and 60%, respectively. Immunostaining intensity of bax correlated with overall survival and death rates: of 57 patients, the 37% with 0 to 1+ intensity had a median survival of 6.6 months, the 63% with 2 to 3+ intensity had a median survival of 31.9 months (P = 0.05); 86% of 19 patients with 0 to 1+ intensity died, and 50% of 36 patients with 2 to 3+ intensity died (P < 0.05). Intensity of bcl-x staining tended to correlate with survival: of the 57 patients with 0 to 1+, 42% had a median survival of 32.7 months compared with 5.8 months in the 58% with 2 to 3+ intensity (P = 0.06). By multivariate analysis, this relationship held for bax (P = 0.011) and bcl-x (P = 0.048). There was no correlation between bcl-2 expression, stage, or gender and prognosis. Patients with baxexpressing HCC experience improved survival compared with those with no or low bax expression, in uni- and multivariate models. Patients with no or low bcl-x tended toward improved survival compared with patients with more bcl-x in their HCC. bcl-2 expression did not correlate with prognosis.