Prognostic value of p27(Kip1) and p21(WAF/Cip) protein expression in muscle invasive bladder cancer

Two genes, namely p27(Kip1) and p21(WAF/Cip1) that reveal distinct structur al homology, have been identified as inductors of cell cycle arrest at the G1-checkpoint to prevent entry of somatic cells into the S phase of the cel l cycle when substantial DNA damage has occurred. It was demonstrated that the p21(WAF/Cip1) gene is induced by pathways dependent and independent fro m a functionally intact p53 tumour suppressor protein. It has been suggeste d that decreased expression both of the p21(WAF/Cip1) and p27(Kip1) protein may contribute to the development of human malignancies due to loss of cri tical antiproliferative mechanisms. So far, the role of altered p21(WAF/Cip 1) mainly of a decreased p27(Kip1) protein expression in patients with musc le invasive bladder cancer has not been investigated. In the present study, 50 tumour specimens from 50 patients undergoing radical cystectomy (T2-T4) were investigated for different biological and clinical characteristics as possible prognostic factors: age, depth of tumour infiltration (T-stage), histological grading (G), lymph node status as well as immunohistochemical staining for the p21(WAF/Cip1) and p27(Kip1) proteins. The median recurrenc e-free survival for patients with and without retained p21(WAF/Cip1) protei n expression was 54 months (3-86 months) and 13 months (1-40 months), respe ctively (p=0.07). During univariate analysis, loss of p21(WAF/Cip1) protein expression (p=0.02), T-stage (p=0.02) and histological grading (p=0.03) we re significant prognostic factors for survival, among which a negative reac tion for the p21(WAF/Cip1) protein (p=0.02) as well as T-stage (p=0.005) re mained independent significant predictors during multivariate analysis. Los s of p27(Kip1) protein expression was not correlated with the recurrence-fr ee or the overall survival of the patients. Prospective studies are needed to confirm the independent prognostic potential of cell-cycle associated pr oteins such as p21(WAF/Cip1) in patients with muscle invasive bladder cance r. The availability of more refined prognostic factors should assist decisi on making regarding the value of more aggressive treatment options, such as adjuvant or neoadjuvant chemotherapy, for defined subgroups of patients.