Clinical significance of p53, mdm2, and bcl-2 proteins in renal cell carcinoma.

ABSTRACT

OBJECTIVES: To improve our understanding of the clinical relevance of p53, mdm2, and bcl-2 protein overexpression in renal cell carcinoma, we retrospectively investigated the immunohistochemical expression of p53, murine double minute 2 (mdm2), and bcl-2 and the relationship of this expression to clinicopathologic characteristics. p53 regulates the transcription of downstream effectors such as the oncoprotein mdm2, and bcl-2 has been shown to inhibit apoptosis triggered by wild-type p53. METHODS: The expression of p53, mdm2, and bcl-2 protein was studied by immunohistochemical methods in paraffin-embedded nephrectomy specimens from 112 patients whose clinicopathologic data confirmed renal cell carcinoma. RESULTS: The expression of the p53 and bcl-2 protein was recognized in 15 (13.4%) and 52 (42.0%) cases, respectively; the expression of the mdm2 protein, however, was seen in only 2 cases (1.8%). No correlation was noted between these three proteins and any clinicopathologic parameters, except p53 expression and Stage T1-2/T3-4 (P = 0.0208). However, in multivariate analysis, stage (hazard ratio 3.586; P = 0.0002), expression of p53 (hazard ratio 6.090; P = 0.0126) and of mdm2 (hazard ratio 22.016; P = 0.0156), and coexpression of p53/mdm2 (hazard ratio 6.146; P = 0.0005) demonstrated a statistically significant effect on prognosis by proportional hazards regression tests. CONCLUSIONS: Our results indicate that stage, p53 expression, mdm2 expression, and coexpression of p53/mdm2 are useful to predict the clinical outcome in patients with renal cell carcinoma.