mdm2 expression as a prognostic indicator in clear cell renal cell cat-cinema: Comparison with p53 overexpression and clinicopathological parameters

The present study was designed to analyze the expression of p53 and mdm2 in clear cell renal cell carcinoma with special emphasis on their association with tumor grade and clinical outcome. In particular, the value of individ ual protein overexpression as well as combined p53/mdm2 positivity was eval uated because both proteins are functionally connected, and their expressio n is controlled by an autoregulatory feedback loop. A cohort of 97 clear ce ll renal cell carcinomas was analyzed. The overexpression of mdm2 and p53 p roteins was investigated on paraffin-embedded material by using monoclonal antibodies, Eighteen tumors showed mdm2 positivity, whereas 35 of the tumor s overexpressed p53. Whereas p53 and mdm2 positivity correlated significant ly (P = 0.00004), no correlation could be found between mdm2 protein overex pression and tumor stage, lymph node involvement, and presence of distant m etastases. mdm2 positivity was found significantly more frequently in tumor s of higher grade. In univariate analysis, there was a statistically signif icant correlation between p53 and mdm2 overexpression in the same tumor and poor survival (P = 0,00179), Multivariate analysis revealed that coinciden t mdm2/p53 overexpression, the presence of distant metastases, and tumor gr ade were independent predictors for tumor progression. Our results indicate that mdm2/p53 co-overexpression, nuclear grade, and preoperative presence of distant metastasis are independent predictors for poor survival.