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P53 and P21-WAF-1-CIPI are not predictors of response to bacillus calmette-guerin (BCG) therapy for superficial bladder cancer

par Zlotta, Alexandre
Référence British journal of urology, 80, SUPPL. 2, page (33)
Publication Publié, 1997

Article révisé par les pairs

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Résumé :

BCG therapy has been demonstrated to be an effective treatment in the prevention of bladder tumor recurrences. However, a significant percentage of patients do not respond to BCG therapy and there are currently very few objective markers which can predict patients who will fail to this treatment. P53 alterations have been demonstrated to be a factor of chemo- and radioresistance. Induction of the p53 tumor suppressor gene activates p21-WAF-1-CIPI which arrests cell growth. We investigated in the present study whether p53 overexpression or p21-WAF-1-CIPI expression could be predictors of response to BCG. An homogenous group of 36 patients with superficial bladder cancer at moderate or high risk for tumor recurrences (patients with pTa, pTl or carcinoma in situ (Cis) with at least one tumor recurrence in the last year, multiple tumors or large tumors) and treated with 6 weekly BCG intravesical instillations (120 mg, Pasteur strain) were included in the study. Expression of p53 (DO7) and p21-WAF-1-CIPI (Ab-1) were determined by immunohistochemistry in paraffin-embedded tissues. Tumor grade was G1, G2, G3 and Cis in 11, 19, 4 and 2 patients respectively while tumor stage was Ta and T1 in 11 and 23 patients respectively. Average follow-up was 28.2 months. Twenty-two patients had a tumor recurrence (61%) with a mean time to recurrence of 12.4 months. Seven out of 22 patients with recurrences had a later cystectomy (31.8%). P53 positive staining (cut-off 10%) occurred in 7/36 patients (19.4%), 2 without and 5 with recurrences (not statistically different). A cut-off of 20% for p53 positive staining resulted in the same absence of statistically significant difference. P53 and p211-WAF-1-CIPI expressions were not correlated. P53 nor p21-WAF-1-CIPI were not significant predictors of time to recurrence or progression to invasive disease. overexpression of p53 is not a common event in superficial bladder cancer and is not a predictor of tumor recurrence or tumor progression to invasive disease in patients who received BCG therapy.