Predictive value of altered p27(Kip1) and p21(WAF/Cip1) protein expressionfor the clinical prognosis of patients with localized prostate cancer

The p21(WAF/Cip) and the p27(Kip1) genes have been identified as inductors of cell cycle arrest at the Gl-checkpoint. Alterations of both genes have b een suggested to be involved in the development of a variety of human malig nancies due to a loss of critical antiproliferative mechanisms. To evaluate the prognostic importance of these alterations for patients with clinicall y localized prostate cancer, in 86 specimens (T1-T4) from 86 patients under going radical prostatectomy at the Department of Urology at Hannover Univer sity Medical School, were investigated. The immunohistochemical expression of the p27(Kip1) and p21(WAF/Cip) protein was correlated to recurrence-free and long-term survival, age, depth of tumour infiltration, histological gr ade and lymph node status in these patients. After a median follow-up of 71 months (1-198 months), 14 of 20 (70%) patients (Group 1) with loss of P27( Kip1) protein expression or a relative amount of < 10% of positively staine d tumour cells developed recurrent disease in contrast to 18 of 66 (27%) pa tients (Group 2) with retained p27(Kip1) protein expression (greater than o r equal to 10% of positively stained tumour cells). The median recurrence-f ree survival times were 39 (4-134) months and 67 (4-198) months for patient s in Groups I and 2 (p <0.01), respectively. In multivariate analysis, loss of p27(Kip1) protein expression was identified as the only independent pro gnostic parameter for recurrence-free survival. Univariate analysis (log-ra nk test) identified histological grading (p<0.01) and reactivity for p27(Ki p1) (p=0.046) (<greater than or equal to>10% positivity) as prognostic fact ors for disease-specific long-term survival. However, during multivariate a nalysis none of the biological variables investigated retained independent prognostic importance regarding overall survival. Neither a low or a high e xpression of p21(Waf/Cip) could be correlated with the clinical prognosis o f the patients following radical prostatectomy. This study confirms the ind ependent prognostic value of decreased p27(Kip1) protein expression in pati ents with localized prostate cancer, while a prognostic importance of p21(W af/Cip) in addition to established patients' and tumour characteristics lik e tumour stage and histological grading appears rather unlikely.