Evaluation of p21^WAF1/CIP1 and cyclin D₁ expression in the progression of superficial bladder cancer

Immunoreactivity of p21(WAF1/CIP1) and cyclin D-1 proteins was assessed in a cohort of 207 patients with superficial (pTa-pT(1)) bladder cancer followed up for a mean of 4.9 years. The results of the immunostainings were compared with T category, WHO grade, tumor cell proliferation rate (MIB-1 score), the expressions of p53 and bcl-2 as well as survival. Sixty-eight percent and 75% of the tumors were p21(WAF1/CIP1) positive (greater than or equal to5% of cells positive) and cyclin D-1 positive (greater than or equal to 10% of cells positive), respectively. The p21(WAF1/CIP1) expression was related to cyclin D-1 immunolabelling (P < 0.001) but not to the other variables studied. The expression of cyclin D-1 was inversely associated with T category (P = 0.001), WHO grade (P = 0.006), MIB-1 score (P = 0.014), p53 expression (P = 0.001), and bcl-2 (P = 0.011) immunoreactivity. In univariate analysis, T category (P = 0.0001), WHO grade (P < 0.0001), MIB-1 score (P < 0.0001) bcl-2 (P = 0.0092), p53 (P = 0.0016) and p21(WAF1/CIP1) (P = 0.009) expressions were significant prognostic factors with regard to tumor progression, whereas cyclin D-1 was without any prognostic significance (P = 0.1). Out of 123 p21 positive tumors 21 progressed, whereas only 2 out of 58 p21 negative tumors progressed. In multivariate analysis, the MIB-1 score was the only independent predictor of cancer-specific survival (P = 0.03), whereas tumor grade (P = 0.002) and cyclin D-1 expression (P = 0.04) were independent predictors of tumor recurrence. Only the WHO grade (P = 0.04) retained its prognostic value indicating the risk of progression. We suggest that in superficial bladder cancer p21(WAF1/CIP1) and cyclin D-1 immunohistochemistry provide no additional prognostic information compared with already established prognostic factors for predicting the risk of progressive disease.