Predictive value of altered p27Kip1 and p21WAF/Cip1 protein expression for the clinical prognosis of patients with localized prostate cancer.
The p21WAF/Cip and the p27Kip1 genes have been identified as inductors of cell cycle arrest at the G1-checkpoint. Alterations of both genes have been suggested to be involved in the development of a variety of human malignancies due to a loss of critical antiproliferative mechanisms. To evaluate the prognostic importance of these alterations for patients with clinically localized prostate cancer, in 86 specimens (T1-T4) from 86 patients undergoing radical prostatectomy at the Department of Urology at Hannover University Medical School, were investigated. The immunohistochemical expression of the p27Kip1 and p21WAF/Cip protein was correlated to recurrence-free and long-term survival, age, depth of tumour infiltration, histological grade 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 p27Kip1 protein expression or a relative amount of < 10% of positively stained tumour cells developed recurrent disease in contrast to 18 of 66 (27%) patients (Group 2) with retained p27Kip1 protein expression (> or = 10% of positively stained tumour cells). The median recurrence-free survival times were 39 (4-134) months and 67 (4-198) months for patients in Groups 1 and 2 (p < 0.01), respectively. In multivariate analysis, loss of p27Kip1 protein expression was identified as the only independent prognostic parameter for recurrence-free survival. Univariate analysis (log-rank test) identified histological grading (p < 0.01) and reactivity for p27Kip1 (p = 0.046) (> or = 10% positivity) as prognostic factors for disease-specific long-term survival. However, during multivariate analysis none of the biological variables investigated retained independent prognostic importance regarding overall survival. Neither a low or a high expression of p21Waf/Cip could be correlated with the clinical prognosis of the patients following radical prostatectomy. This study confirms the independent prognostic value of decreased p27Kip1 protein expression in patients with localized prostate cancer, while a prognostic importance of p21Waf/Cip in addition to established patients' and tumour characteristics like tumour stage and histological grading appears rather unlikely.
Kuczyk
M A
MA
Department of Urology, Urologic Oncology Research Group (basic), Hannover University Medical School, D-30625 Hannover, Germany. kuczyk.markus@mh-hannover.de
Bokemeyer
C
C
Hartmann
J
J
Schubach
J
J
Walter
C
C
Machtens
S
S
Knuchel
R
R
Kollmannsberger
C
C
Jonas
U
U
Serth
J
J
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000368:Aged; D015415:Biomarkers; D018797:Cell Cycle Proteins / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D015415:Biomarkers; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27