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

• Published in: International journal of urology 2000-12, Vol.7 (12), p.457-463
• Main Authors: Hashimoto, Hiroshi, Sue, Yoichi, Saga, Yuji, Tokumitsu, Masayuki, Yachiku, Sunao
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Carcinoma, Transitional Cell - metabolism; Carcinoma, Transitional Cell - pathology; Cell Division - physiology; Disease Progression; Female; Humans; Ki-67; Ki-67 Antigen - metabolism; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Kidney Pelvis; Male; MDM2; Middle Aged; Multivariate Analysis; Neoplasm Invasiveness; Neoplasm Staging; Nuclear Proteins; p53; Prognosis; Proto-Oncogene Proteins - physiology; Proto-Oncogene Proteins c-mdm2; renal pelvis and ureter; Survival Analysis; transitional cell carcinoma; Tumor Suppressor Protein p53 - physiology; Ureteral Neoplasms - metabolism; Ureteral Neoplasms - pathology
• ISSN: 0919-8172; 1442-2042
• DOI: 10.1046/j.1442-2042.2000.00230.x

Background The significance of p53 overexpression for the prognosis of transitional cell carcinoma (TCC) of the renal pelvis and ureter remains controversial. Simultaneous evaluation of p53 and MDM2 may enable better prediction of tumor proliferation and patient prognosis than that obtained with evaluation of p53 alone. Methods Immunohistochemical detection of p53 protein, MDM2 protein and Ki‐67 antigen as proliferation markers was performed for tissue samples obtained from 74 patients with TCC of the renal pelvis and ureter. The correlations of p53/MDM2 overexpression with conventional pathological features, Ki‐67 labelling index (LI) and patient survival were studied. Results Overexpression of p53 was related to progression of each of the pathological 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 analyses were performed for 66 patients. Univariate analysis showed p53 to be a useful prognostic indicator, but in a multivariate analysis only type of infiltration and Ki‐67 LI were independent survival markers, while p53 was not. Overexpression of MDM2 was unrelated to patient survival, and the combination of p53 and MDM2 for survival indication was found not to be useful. Conclusions Overexpression of p53 is related to disease progression, increased tumor proliferation and patient survival for TCC of the renal pelvis and ureter, but the independent prognostic value of p53 did not reach statistical significance. Combined analysis of MDM2 with p53 cannot be recommended for examination of the malignant potential of TCC of the renal pelvis and ureter.