Correlation and prognostic significance of p53, A21WAF1/CIP1 and Ki-67 expression in patients with superficial bladder tumors treated with bacillus Calmette-Guerin intravesical therapy

被引:102
作者
Zlotta, AR [1 ]
Noel, JC
Fayt, I
Drowart, A
Van Vooren, JP
Huygen, K
Simon, J
Schulman, CC
机构
[1] Erasme Univ Hosp, Dept Urol, B-1070 Brussels, Belgium
[2] Erasme Univ Hosp, Dept Pathol, B-1070 Brussels, Belgium
[3] Erasme Univ Hosp, Dept Chest & Immunodeficiency Dis, B-1070 Brussels, Belgium
[4] Pasteur Inst Brussels, Dept Mycobacterial Immunol, B-1070 Brussels, Belgium
关键词
bladder cancer; BCG; p53; p21; Ki-67;
D O I
10.1016/S0022-5347(01)61770-1
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose: We determine if, before intravesical bacillus-Calmette Guerin (BCG) therapy, p53, p21(WAF-1-CIP1) (a critical downstream effector of p53 pathway of cell growth control, inhibiting cyclin dependent kinases) and the cell proliferation marker Ki-67 (MIB-1) could be used as prognostic markers of response to BCG in patients with superficial bladder tumors. Materials and Methods: The study included 47 patients with superficial bladder tumors at high risk for recurrence or progression treated with 6 weekly intravesical BCG instillations. We analyzed p53, p21 and Ki-67 on paraffin embedded samples by immunohistochemistry and the percentage of positive cells was determined in a blinded fashion. Quantitative immunostaining was analyzed in relation to time to recurrence and progression using univariate or multivariate analysis and the Kaplan-Meier method. Results: During a mean followup of 24.6 months 23 of the 47 patients (48.9%) presented with tumor recurrence and 10 (21.2%) had later progression to invasive disease. A p21 over expression (greater than 10%) was observed in 23 tumors (48.9%) and positively correlated with p53 (p = 0.0097) but not with Ki-67 (p = 0.327). Of the tumors 18 (38.2%) were p53 and p21 negative. Among p21 positive tumors 15 (65.2%) were p53 and p21 positive, suggesting that p21 may also be regulated by p53 independent pathways. However, p53 did not act as a predictor of recurrence or progression. In contrast, using Kaplan-Meier curves p21 over expression (greater than 10%) and Ki-67 at a 25% cutoff were associated with shorter recurrence-free survival (both p = 0.02 log rank test) but they did not predict additional information about risk of progression. However, multivariate analysis failed to demonstrate any independent prognostic value for p21 or Ki-67 in contrast to tumor stage. Conclusions: Our results indicate that p21(WAF-1-CIP1) seems to be regulated by p53 independent pathways in superficial bladder cancer. The present study did not indicate an independent prognostic significance in patients treated with BCG for p53, p21(WAF-1-CIP1) or Ki-67 markers. Larger prospective studies are needed to evaluate further the independent value of these biological markers in superficial bladder cancer management.
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收藏
页码:792 / 798
页数:7
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