© 1998 by Oxford University Press
Journal Of The National Cancer Institute, Vol 90, 1072-1079, Copyright © 1998 by Oxford University Press
JP Stein, DA Ginsberg, GD Grossfeld, SJ Chatterjee, D Esrig, MG Dickinson, S Groshen, CR Taylor, PA Jones, DG Skinner and RJ Cote
BACKGROUND: Altered expression of p53 protein is an important predictor of
progression in bladder cancer. The action of p53 on cell cycle regulation
is mediated, in part, through expression of the cyclin- dependent kinase
inhibitor p21WAF/CIP1 (p21). Loss of p21 expression may, therefore,
contribute to tumor progression. We sought to determine the relationship
between p21 expression in bladder cancer and disease progression. METHODS:
Tumor specimens were obtained from 242 patients who underwent cystectomy
for bladder cancer. Median follow-up was 8.5 years (range, 0.1-11.8 years).
Nuclear p21 status was determined by immunohistochemistry and was then
analyzed in relationship to the probability of tumor recurrence, overall
survival, and tumor p53 status. Reported P values are two-sided. RESULTS:
Nuclear p21 expression was detected in the tumors of 156 (64%) of the 242
patients. Patients with p21-positive tumors had a decreased probability of
tumor recurrence (P<.00001) and an increased probability of overall
survival (P<.00001) in comparison with patients with p21-negative
tumors. In a multivariable analysis, p21 expression was an independent
predictor of tumor recurrence (P = .0017) and of survival (P = .006) when
assessed with tumor grade, tumor stage, lymph node status, and p53 status.
p21 expression was associated with p53 status (P<.001); 56% of tumors
with p53 alterations showed loss of p21 expression, whereas 79% of tumors
expressing wild-type p53 were p21 positive. Patients with p53-
altered/p21-negative tumors demonstrated a higher rate of recurrence and
worse survival compared with those with p53-altered/p21-positive tumors
(P<.0001). Patients with 53-altered/p21-positive tumors demonstrated a
similar rate of recurrence and survival as those with p53-wild type tumors.
CONCLUSION: Loss of p21 expression is a statistically significant and
independent predictor of bladder cancer progression. Maintenance of p21
expression appears to abrogate the deleterious effects of p53 alterations
on bladder cancer progression.
ARTICLES
Effect of p21WAF1/CIP1 expression on tumor progression in bladder cancer
Department of Pathology, University of Southern California School of Medicine and Kenneth Norris Jr. Comprehensive Cancer Center, Los Angeles 90033, USA.
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