Prognostic significance of p27Kip1 expression in bladder cancer

Objective To define the prognostic significance of p27(Kip1) expression in bladder cancer for overall, disease-specific, metastasis-free and pelvic recurrence-free survival, and to identify clinical and pathological correlates of p27(Kip1) immunophenotypes. Patients and methods Tumour samples from 128 evaluable patients with bladder cancer were assessed by immunohistochemistry for p27(Kip1) and E2F-1 expression. Immunoreactivity of p27(Kip1) was correlated with clinicopathological variables, E2F-1 immunoreactivity, and outcome. Multivariate analysis was used to assess predictors of outcome. The median follow-up was 30.9 months overall and 105.7 months in the 32 patients alive at the last follow-up. ResultsThe fraction of tumour cells with p27(Kip1) nuclear immunoreactivity was < 5% in 15, 5-25% in 30, 25-50% in 19, 50-75% in 51, and >= 75% in 13 patients. High-grade tumours and those with lower E2F-1 nuclear reactivity had a lower mean percentage p27(Kip1) reactivity (P = 0.047 and 0.011, respectively). On multivariate analysis, the percentage p27(Kip1) reactivity was a significant independent predictor of pelvic recurrence (P = 0.017), progression to metastases (P = 0.046), death from disease (P = 0.008), and death from any cause (P = 0.017), with a low expression portending a worse prognosis. Suspicion of vascular invasion was a significant independent predictor of progression to metastases (P = 0.002), death from disease, and death from any cause (both P < 0.001). Lymph node involvement was a significant independent predictor of progression to metastases (P = 0.006). Conclusions Low expression of p27(Kip1) was a significant independent predictor of pelvic recurrence, progression to metastasis, death from disease and death from any cause, in patients with bladder cancer.