THE PROGNOSTIC VALUE OF P53 NUCLEAR OVEREXPRESSION AND MIB-1 AS A PROLIFERATIVE MARKER IN TRANSITIONAL-CELL CARCINOMA OF THE BLADDER

BACKGROUND, There is controversy regarding the value of biologic marke rs as prognostic indicators independent of clinicopathologic parameter s in transitional cell carcinoma (TCC) of the bladder. The authors exa mined the prognostic value of p53 tumor suppressor gene expression and the proliferative marker MIB-1 in TCC of the bladder. METHODS, Fresh frozen samples from 114 TCCs of the bladder and 13 normal bladders wer e studied by immunohistochemistry, using monoclonal antibodies MIB-1 f or proliferation and PAb 1801 for p53 nuclear overexpression. Scores w ere determined in each case by counting at least 500 nuclei per slide in 3-5 selected regions. Patients were stratified for both markers int o two groups for time-event analysis, according to the median number o f nuclei stained. Patients with nuclear staining below the median valu e of the score were considered negative in the statistical analysis. Q uantitative immunostaining was analyzed in relation to the time to rec urrence, progression, and cancer death, and compared with clinical and pathologic parameters for prognostic significance in univariate and m ultivariate analysis (stepwise logistic regression). RESULTS, Median n uclear overexpression of p53 was 22% and that of MIB-1 28%. There was a strong association between proliferation and p53 nuclear overexpress ion (P < 0.0001). Progression free and disease specific survival rate estimates (log rank test) were significantly lower in patients with p5 3 or MIB-1 scores above 22% and 28%, respectively. Multivariate analys is indicated that stage as well as p53 and MIB-1 immunostaining provid ed independent prognostic information. CONCLUSIONS, Quantitative immun ohistochemical evaluation of nuclear p53 and MIB-1 immunostaining inex pensively provides prognostic indicators in cases of TCC of the bladde r. (C) 1997 American Cancer Society.