Expression of cyclin A and D proteins in prostate cancer and their relation to clinopathological variables and patient survival

BACKGROUND. Cell proliferation and its regulation are important determinant s of the prognosis of prostate cancer patients. Cyclins are important regul ators of cell proliferation in human cancer, but their prognostic value has not been previously analyzed in prostate cancer. METHODS. The immunohistochemical expression and prognostic value of cyclins A and D were studied in prostate cancer in a cohort of 213 patients follow ed-up for a mean of 12 years. RESULTS. The expression of cyclin A was both cytoplasmic and nuclear, where as the expression of cyclin D was nuclear. The mean (SD) fraction of cyclin A- and cyclin D-positive cells was 2.1 (7.9)% and 16.3 (23.4)%, respective ly. The expression of cyclin A was related to TM-category, histological dif ferentiation, perineural invasion, S-phase fraction, and expression of Ki67 and bcl-2 (for all, P < 0.05). The expression of cyclin D was related to c lassification, histological differentiation, perineural invasion, DNA ploid y, S-phase fraction, expression of Ki67, and mitotic index (for all, P less than or equal to 0.01). In survival analysis, expression of cyclin A predi cted cancer-related survival in the entire cohort (P < 0.001). Expression o f cyclin D predicted cancer-related survival in the entire cohort (P < 0.00 01), in MO (P = 0.0007), and in T1-2NxM0 tumors (P = 0.0003). in Cox multiv ariate analysis, T-category, M-category, patient age, and the fraction of c yclin A-positive cells were independent predictors of survival in the entir e series. In local tumors, T-category, Gleason score, DNA ploidy, or S-phas e fraction were independent prognostic factors, and cyclins had no independ ent prognostic value. CONCLUSIONS. The results show that the expression of cyclins A and D is rel ated to several malignant cellular features in prostate cancer, but they ha ve no independent prognostic value. (C) 1999 Wiley-Liss, Inc.