P53, BCL-2, AND BAX EXPRESSION IN RENAL-CELL CARCINOMA

Objectives, Renal cell carcinomas often show a high degree of resistan ce to chemotherapy and radiation despite expressing normal function of the protein p53. The loss of control of apoptosis may also contribute to progression and resistance to treatment modalities and can be attr ibuted to an interaction between p53 and the apoptotic regulators bcl- 2 and Bax. To determine whether the expression of p53, bcl-2, or Bar c ould be correlated with outcome, we analyzed the expression pattern of these proteins in renal cell tumor samples, Methods. We examined 28 p atients with clear cell renal cell carcinomas along with 7 patients wi th papillary renal cell carcinomas and 4 with renal oncocytomas. All r enal cell carcinomas were clinically localized Stage pT2 with tumor si ze ranging from 4.0 to 10.3 cm (mean 6.23). Immunohistochemistry was p erformed on all samples and correlated with markers of outcome, includ ing tumor grade, metastasis, recurrence, and overall survival rate. Re sults. In all clear cell tumors, the detection level of p53 expression was below the sensitivity of the assay, consistent with the reported infrequent incidence of p53 mutations in renal cell cancers. bcl-2 exp ression showed a significant correlation (P = 0.018) with higher tumor grade but could not be significantly correlated with other parameters examined including tumor recurrence, metastasis, or survival rate. Th e expression of Bar could similarly be correlated with higher tumor gr ade but with none of the other parameters. Conclusions. At the present time, the combination of both tumor grade and stage represents the be st prognostic markers available. Adjunctive use of bcl-2 and Bar stain ing currently plays a minimal role in helping to further stratify pati ents at high risk for disease progression or recurrence. (C) 1998, Els evier Science Inc. All rights reserved.