Prognostic significance of cell cycle-associated genes p27(Kipf) and p21(WAF/Cip) for muscle-invasive carcinoma

Purpose: The p27(Kopl) and p21(WAF/Clp) genes have been identified as induc tors of cell cycle arrest at the G1-checkpoint to prevent entry of somatic cells into the S phase of the cell cycle. it has been suggested that decrea sed expression both of the p21(WAF/Clp) and p27(Kip1) protein may contribut e to the development of human malignancies due to loss of critical antiprol iferative mechanisms. The role of an altered p21(WAF/Clp) and mainly of a d ecreased p27(Kip1) protein expression in patients with muscle invasive blad der cancer has not been investigated to date. Material and Methods: In the present study 50 tumour specimens from 50 patients undergoing radical cyste ctomy (T2-T4) for the treatment of muscle invasive bladder cancer were inve stigated for different biological and clinical characteristics as possible prognostic factors: age, depth of tumour infiltration (T-stage), histologic al grading (G), lymph node status as well as immunohistochemical staining f or the p21(WAF/Clp) and p27(Kip1) proteins. Results: The median recurrence- free survival for patients with and without retained p21(WAF/Clp) protein e xpression was 54 months (3-86 months) and 13 months (1-40 months), respecti vely (p=0.07). Therefore, regarding loss of p21(WAF/Clpl) protein expressio n as a predictor of the recurrence-free survival since radical cystectomy, the level of statistical significance was hardly missed. In univariate anal ysis the toss of p21(WAF/Clp) protein expression (p=0.02), T-stage (p=0.02) and histological grading (p=0.03) were significant prognostic factors for survival, of which a negative reaction for the p21(WAF/Clp) protein (p = 0. 02) as well as T-stage (p = 0.005) remained independent significant predict ors in multivariate analysis. Conclusion: The additional prognostic value o f an inactivation of the p21(WAF/Clp) gene for muscle-invasive bladder canc er should be investigated further by prospective trials.