p53 and MDM2 in Renal Cell Carcinoma: Biomarkers for Disease Progression and Future Therapeutic Targets?

• Published in: Cancer Vol. 116; no. 4; pp. 780 - 790
• Main Authors: NOON, Aidan P, VLATKOVIC, Nikolina, POLANSKI, Radosław, MAGUIRE, Maria, SHAWKI, Howida, PARSONS, Keith, BOYD, Mark T
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley-Blackwell 15.02.2010
• Subjects: Biological and medical sciences; Biomarkers, Tumor; Carcinoma, Renal Cell - genetics; Cell Line, Tumor; Disease Progression; Genes, p53; Humans; Kidney Neoplasms - genetics; Kidneys; Medical sciences; Mutation; Nephrology. Urinary tract diseases; Prognosis; Proto-Oncogene Proteins c-mdm2 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors; Tumors of the urinary system; Up-Regulation; Kidney disease; Urinary system disease; Carcinoma; Targeting; Targeted therapy; murine double minute 2; Biological marker; renal cancer; Malignant tumor; mdm2 Gene; p53; renal cell carcinoma; Cancerology; TP53 Gene; C-Onc gene; Kidney cancer; Grawitz tumor; Protooncogene; Cancer; Tumor suppressor gene
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.24841

Renal cell carcinoma (RCC) is the most common type of kidney cancer and follows an unpredictable disease course. To improve prognostication, a better understanding of critical genes associated with disease progression is required. The objective of this review was to focus attention on 2 such genes, p53 and murine double minute 2 (MDM2), and to provide a comprehensive summary and critical analysis of the literature regarding these genes in RCC. Information was compiled by searching the PubMed database for articles that were published or e-published up to April 1, 2009. Search terms included renal cancer, renal cell carcinoma, p53, and MDM2. Full articles and any supplementary data were examined; and, when appropriate, references were checked for additional material. All studies that described assessment of p53 and/or MDM2 in renal cancer were included. The authors concluded that increased p53 expression, but not p53 mutation, is associated with reduced overall survival/more rapid disease progression in RCC. There also was evidence that MDM2 up-regulation is associated with decreased disease-specific survival. Two features of RCC stood out as unusual and will require further investigation. First, increased p53 expression is tightly linked with increased MDM2 expression; and, second, patients who have tumors that display increased p53 and MDM2 expression may have the poorest overall survival. Because there was no evidence to support the conclusion that p53 mutation is associated with poorer survival, it seemed clear that increased p53 expression in RCC occurs independent of mutation. Further investigation of the mechanisms leading to increased p53/MDM2 expression in RCC may lead to improved prognostication and to the identification of novel therapeutic interventions.