EVALUATION OF OVEREXPRESSION OF P53 TUMOR-SUPPRESSOR PROTEIN IN SUPERFICIAL AND INVASIVE TRANSITIONAL-CELL BLADDER-CANCER - COMPARISON WITHDNA-PLOIDY

Objectives. p53 tumor suppressor gene is considered to play a signific ant role in carcinogenesis. Mutations in the p53 are the most frequent genetic abnormalities encountered in human malignancies. Our aim was to investigate the expression of p53 oncoprotein in superficial and in vasive transitional cell bladder cancer (TCC) as well as its correlati on with established prognostic factors, such as histologic grade, tumo r stage, DNA content, and survival. Methods. Forty-five patients with superficial TCC (Ta-T1) and 42 with invasive TCC (T2-T4) were included in our study. Material from transurethral biopsy was examined using a n immunohistochemical method and the monoclonal antibody Pab 1801. Res ults. p53 tumor suppressor protein was overexpressed in 48.3% of TCC c ases and more frequently in invasive than superficial TCCs (P = 0.03) and undetectable in the tumor adjacent to normal tissue. p53 positivit y was related to the degree of differentiation and with the stage of t he disease of invasive TCCs (P = 0.03 and P = 0.004, respectively), wh ereas no statistical significance was documented for superficial TCCs. Moreover, p53 overexpression demonstrated a statistical significance with DNA ploidy in superficial Ta-T1 tumors (P = 0.04) and was suggest ive in invasive T2-T4 tumors (P = 0.08). There was no correlation of r ecurrence related to p53-positive superficial tumors (P = 0.29). Patie nts with p53-positive invasive TCCs showed statistically significant w orse survival (P = 0.007), but in multivariate analysis, p53 positivit y is not independently related to poor overall survival (P = 0.30). Wh en we combined ploidy and p53 status, we realized that the subset of p atients with aneuploidy and p53 positivity had the worst prognosis (P = 0.008). Conclusions. The results suggest the involvement of p53 prot ein as a ]ate event in bladder carcinogenesis. p53 does not seem to be a prognostic marker for recurrences of superficial tumors and is not independently related to survival. The aneuploidy of tumors correlates with the p53 positivity in bladder cancer. The combined expression of aneuploidy and p53 positivity in invasive tumors has strong associati on with the survival of patients.