Original article Conventional (clear cell) renal carcinoma metastases have greater bcl-2 expression than high-risk primary tumors

Bcl-2 antagonizes p53-induced apoptosis and may contribute to chemoresistance. In renal cell carcinoma (RCC), the role of bcl-2 is not well-defined, though its expression is reportedly low in primary tumors and lacks prognostic value. This study evaluates patterns of bcl-2 expression in high-risk (pT3) primary tumors and in matched patient metastases. Immunohistochemical analysis of bcl-2 was performed on 149 cases of conventional (clear cell) RCC (112 pT3 primaries, 37 metastases). Paraffin-embedded tissues were obtained from nephrectomies and metastatic resections. Median follow up was 48 months in the entire cohort and 69 months in living patients. We evaluated associations between bcl-2 expression and tumor recurrence or patient survival with the Cox regression test, and used the t-test and Pearson correlation methods to evaluate bcl-2 expression in primary and metastatic cases. Bcl-2 expression was observed at a higher frequency in metastases (21/37 cases; 57%) compared to primary tumors (24/112 cases; 21%; P 0.001). The percentage of cells stained was greater in metastases than primary tumors (P 0.003). This finding was also noted when expression in metastatic cases was compared with matched primaries (P 0.05). Bcl-2 expression did not predict disease-free ( P 0.30), disease-specific (P 0.90), or overall (P 0.51) survival. Most RCC primary tumors have low-to-absent levels of bcl-2 protein, whereas most RCC metastases display greater protein levels. Bcl-2 expression in primary tumors does not predict clinical outcome. However, expression of bcl-2 protein occurs at a high frequency in RCC metastases when compared to primary tumors. It may be reasonable to target RCC patients displaying altered bcl-2 levels for molecular therapies, such as anti-bcl2, should metastatic disease develop. © 2003 Elsevier Inc. All rights reserved.