P53 and MDM2 Over-expression and Five-year Survival of Kidney Cancer Patients Undergoing Radical Nephrectomy - Iranian Experience

Background: Relatively little is known with certainty about the status and role of p53 or MDM2 in predictingprognosis and survival of renal cell carcinoma. The present study aimed to determine the value of P53 and MDM2over-expression, alone and simultaneously, to predict five-year survival of patients with kidney cancer in Iran.Materials and
Methods: Patients with kidney cancer referred to Hasheminejad Kidney Center between 2007and 2009, underwent radical nephrectomy and had pathology reports of clear cell, papillary or chromophoberenal cell carcinoma were included in our cohort study. Other histological types of renal cell carcinoma werenot included. The patients with missed, incomplete or poor quality paraffin blocks were also excluded. Overallninety one patients met the inclusion and exclusion criteria. To assess the histopathological features of the tumor,immunohistochemical (IHC) staining of formalin fixed, paraffin-embedded tumor samples were performed.The five-year survival was determined by the patients’ medical files and telephone following-up.
Results: Intotal, 1.1% of all samples were revealed to be positive for P53. Also, 20.8% of all samples were revealed to bepositive for MDM2.The patients were all followed for 5 years. In this regard, 5-year mortality was 30.5% andthus 5-year survival was 85.3%. According to the Cox proportional hazard analysis, positive P53 marker wasonly predictor for patients’ 5-year survival that the presence of positive p53 increased the risk for long-termmortality up to 2.8 times (HR=2.798, 95%CI: 1.176-6.660, P=0.020). However, the presence of MDM2 couldnot predict long-term mortality. In this regard, analysis by the ROC curve showed a limited role for predictinglong-term survival by confirming P53 positivity (AUC=0.610, 95%CI: 0.471-.750, P=0.106). The best cutoffpoint for P53 to predict mortality was 0.5 yielding a low sensitivity (32.0%) but a high specificity (97.9%). Insimilar analysis, measurement of MDM2 positivity could not predict mortality (AUC=0.449, 95%CI: 0.316-.583,P=0.455).
Conclusions: The simultaneous presence of both P53 and MDM2 markers in our population is a rarephenomenon and the presence of these markers may not predict long-term survival in patients who undergoingradical nephrectomy.