p53 protein expression but not mdm-2 protein expression is associated with rapid tumor cell proliferation and prognosis in renal cell carcinoma

Abstract

The clinical course of renal cell carcinoma (RCC) is highly variable. Overexpression of the p53 protein has been suggested as a possible prognostic parameter in RCC. Overexpression of the mdm-2 oncogene product has been shown to interact with the p53 function. To investigate the immunohistochemical overexpression of mdm-2 protein in comparison with that of p53 protein in RCC, 50 nonpapillary pT3 RCCs were immunostained for p53 protein (DO-7) and mdm-2 (IF2). Tumor growth fraction (Ki-67 labeling index; MIB-1) was determined by immunohistochemistry, p53 positivity was detected in 16% of tumors, mdm-2 overexpression was seen in 30% of RCCs. There was a significant association between p53 and mdm-2 immunostaining (P = 0.0006), suggesting that mdm-2 protein may contribute to p53 protein stabilization in RCC. p53 overexpression was associated with a high Ki-67 LI (P = 0.0002), suggesting that p53 overexpression is involved in growth control in RCC. Survival analysis showed that Ki-67 LI (P=0.04) and p53 overexpression were as sociated with poor prognosis (P = 0.0021), whereas mdm-2 overexpression was not related to patient outcome (P---0.73). A Cox regression analysis revealed tumor stage (P<0.001) and p53 overexpression (P<0.05) to be independent prognostic parameters. It is concluded that p53 but not mdm-2 may be of practical relevance in predicting patient prognosis in RCC.

Molecular Signatures of Localized Clear Cell Renal Cell Carcinoma to Predict Disease-Free Survival after Nephrectomy

“…Mutant p53 forms are detectable by immunohistochemistry due to its extended half-life. Mutant p53 expression is found in 20% to 50% of renal tumors and varies by histologic subtype (27,42,43). Our study confirms that higher p53 protein staining is associated with poor prognosis (27,42,44).…”

Selected immunohistochemical features of conventional renal cell carcinomas coexpressing P53 and MDM2

“…They also observed, similar to our study, an association between P53 and Ki-67 expression. On the other hand, Moch et al reported that Ki-67 expression appeared to be related to survival; however, when evaluated using a multivariate model, only the influence of P53 and stage remained significant [37].…”

An overview of renal cell cancer: Pathology and genetics

“…The relationship of leiomyomatous renal cell carcinoma and clear cell papillary renal cancer based on the presence or absence of VHL mutation and/or 3p losses is currently controversial. Apart from the VHL inactivation as an initiating event in clear cell renal cancer, many different genetic alterations have been reported for this tumor type, some of them associated with prognosis [55][56][57][58][59][60][61][62][63][64][65][66][67].…”