Roles of p53 and MDM2 in tumor proliferation and determination of the prognosis of transitional cell carcinoma of the renal pelvis and ureter

Background: The significance of p53 overexpression for the prognosis of tra nsitional cell carcinoma (TCC) of the renal pelvis and ureter remains contr oversial. Simultaneous evaluation of p53 and MDM2 may enable better predict ion of tumor proliferation and patient prognosis than that obtained with ev aluation of p53 alone. Methods: Immunohistochemical detection of p53 protein, MDM2 protein and Ki- 67 antigen as proliferation markers was performed for tissue samples obtain ed from 74 patients with TCC of the renal pelvis and ureter. The correlatio ns of p53/MDM2 overexpression with conventional pathological features, Ki-6 7 labelling index (LI) and patient survival were studied. Results: Overexpression of p53 was related to progression of each of the pa thological features examined (grade, stage, type of infiltration, vascular invasion and lymphatic invasion) and Ki-67 LI was significantly higher with high p53 expression than with low p53 expression. However, overexpression of MDM2 was related to neither disease progression nor Ki-67 LI. Survival a nalyses were performed for 66 patients. Univariate analysis showed p53 to b e a useful prognostic indicator, but in a multivariate analysis only type o f infiltration and Ki-67 LI were independent survival markers, while p53 wa s not. Overexpression of MDM2 was unrelated to patient survival, and the co mbination of p53 and MDM2 for survival indication was found not to be usefu l. Conclusions: Overexpression of p53 is related to disease progression, incre ased tumor proliferation and patient survival for TCC of the renal pelvis a nd ureter, but the independent prognostic value of p53 did not reach statis tical significance. Combined analysis of MDM2 with p53 cannot be recommende d for examination of the malignant potential of TCC of the renal pelvis and ureter.