title: 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 associated 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.
authors.affiliation: Institute of Pathology, University of Basel, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Moch
authors.forename: G
authors.initials: G
authors.lastname: Sauter
authors.forename: T C
authors.initials: TC
authors.lastname: Gasser
authors.forename: N
authors.initials: N
authors.lastname: Buchholz
authors.forename: L
authors.initials: L
authors.lastname: Bubendorf
authors.forename: J
authors.initials: J
authors.lastname: Richter
authors.forename: F
authors.initials: F
authors.lastname: Jiang
authors.forename: A
authors.initials: A
authors.lastname: Dellas
authors.forename: M J
authors.initials: MJ
authors.lastname: Mihatsch
mesh_terms: D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000378:metabolism*; D002455:Cell Division; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D012044:Regression Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2