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. RESULTS: The 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.