The predictive value of p53, p27Kip1, and α-catenin for progression in superficial bladder carcinoma

Objective: The aim of the study was to confirm the predictive value of cell cycle regulatory proteins, p53 and p27(kip1), and the cell adhesion complex protein a-catenin, for progression in patients with superficial bladder carcinoma. Methods: Forty-one patients with progression after primary superficial bladder carcinoma were individually matched to patients with nonprogressive superficial bladder carcinoma. Matching was done for sex, age, tumor stage and grade, concomitant carcinoma in situ (CIS), and duration of follow-up. Immunohistochemical analysis of p53, p27(kip1), and alpha-catenin was performed on each primary bladder tumor. Analysis for the p53 mutation was done on 41 bladder tumor samples. Conditional logistic regression analysis was used to establish the prognostic value of immunohistochemical p53, p27(kip1), and alpha-catenin status. Results: The independent odds ratios for progression were 0.3 (95% confidence interval [CI], 0.1-1.2) for high-risk p27(kip1), 3.4 (95%CI, 0.8-15.2) for high-risk p53, and 2.5 (95%CI, 0.6-10.3) for high-risk alpha-catenin. Combinations of different markers had no synergistic effects. Two p53 mutations were found in 21 DNA samples analyzed from nonprogressive tumors (9.5%); 8 of 20 samples (40%) from progressive tumors showed a p53 mutation. The probability of high-risk p53 immunostaining was 5-fold increased in case of mutations in p53. The estimated positive predictive value of high-risk p53 or high-risk a-catenin was about 23%. Conclusions: We confirm that high-risk p53, p53 mutation, and alpha-catenin immunohistochemistry do have an additional prognostic value in primary bladder carcinoma. However, the clinical value of the investigated parameters remains limited. (c) 2005 European Association of Urology. Published by Elsevier B.V. All rights reserved.