Renal cell carcinoma MIB-1, Bax and Bcl-2 expression and prognosis

Proliferation and programmed cell death (apoptosis) are key factors in oncogenesis and tumor progression. In carcinogenesis important regulators of apoptosis are members of the Bcl-2 family. In this family the Bcl-2 gene has an inhibitory effect on apoptosis, while Bax promotes cell death. In renal cell carcinoma (RCC) the associations between Bcl-2 proteins and RCC prognosis have been controversial. We evaluated Bax and Bcl-2 levels in RCC, and their associations with prognosis, proliferation and traditional prognostic factors.

Our prospective study population comprised 138 consecutive patients who underwent radical nephrectomy for RCC. Immunostaining and semiquantitative indices for Ki-67 (MIB-1), Bax and Bcl-2 were estimated. Their associations with prognosis were explored.

On univariate analysis according to survival statistically significant differences were achieved by Bax (positive vs negative HR 3.04, 95% CI 1.27 to 7.23), Bcl-2 (positive vs negative HR 0.43, 95% CI 0.23 to 0.81), MIB-1 (continuous HR 1.03, 95% CI 1.001 to 1.064), Fuhrman nuclear class (4 vs 1 plus 2 HR 8.15, 95% CI 3.13 to 21.20) and stage (4 vs 1 HR 60.04, 95% CI 13.99 to 257.68). Only stage (HR 47.96, 95% CI 10.85 to 212.03) and Fuhrman classification (HR 4.32, 95% CI 1.60 to 11.65) attained statistical significance on Cox regression multivariate analysis.

In our prospective study Bax and Bcl-2 showed a statistically significant association with prognosis in RCC but did not achieve the status of independent prognostic factors. Further studies are needed to clarify the role of the apoptotic process in tumor progression and prognosis.