BACKGROUND: Cell proliferation and its regulation are important determinants of the prognosis of prostate cancer patients. Cyclins are important regulators 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 followed-up for a mean of 12 years. RESULTS: The expression of cyclin A was both cytoplasmic and nuclear, whereas 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)%, respectively. The expression of cyclin A was related to TM-category, histological differentiation, 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 TM-classification, histological differentiation, perineural invasion, DNA ploidy, S-phase fraction, expression of Ki67, and mitotic index (for all, P< or =0.01). In survival analysis, expression of cyclin A predicted cancer-related survival in the entire cohort (P<0.001). Expression of cyclin D predicted cancer-related survival in the entire cohort (P<0.0001), in MO (P = 0.0007), and in T1-2NxM0 tumors (P = 0.0003). In Cox multivariate analysis, T-category, M-category, patient age, and the fraction of cyclin A-positive cells were independent predictors of survival in the entire series. In local tumors, T-category, Gleason score, DNA ploidy, or S-phase fraction were independent prognostic factors, and cyclins had no independent prognostic value. CONCLUSIONS: The results show that the expression of cyclins A and D is related to several malignant cellular features in prostate cancer, but they have no independent prognostic value.
BACKGROUND: Cell proliferation and its regulation are important determinants of the prognosis of prostate cancerpatients. Cyclins are important regulators of cell proliferation in humancancer, 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 followed-up for a mean of 12 years. RESULTS: The expression of cyclin A was both cytoplasmic and nuclear, whereas 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)%, respectively. The expression of cyclin A was related to TM-category, histological differentiation, 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 TM-classification, histological differentiation, perineural invasion, DNA ploidy, S-phase fraction, expression of Ki67, and mitotic index (for all, P< or =0.01). In survival analysis, expression of cyclin A predicted cancer-related survival in the entire cohort (P<0.001). Expression of cyclin D predicted cancer-related survival in the entire cohort (P<0.0001), in MO (P = 0.0007), and in T1-2NxM0 tumors (P = 0.0003). In Cox multivariate analysis, T-category, M-category, patient age, and the fraction of cyclin A-positive cells were independent predictors of survival in the entire series. In local tumors, T-category, Gleason score, DNA ploidy, or S-phase fraction were independent prognostic factors, and cyclins had no independent prognostic value. CONCLUSIONS: The results show that the expression of cyclins A and D is related to several malignant cellular features in prostate cancer, but they have no independent prognostic value.
Authors: Craig J Burd; Christin E Petre; Lisa M Morey; Ying Wang; Monica P Revelo; Christopher A Haiman; Shan Lu; Cecilia M Fenoglio-Preiser; Jiwen Li; Erik S Knudsen; Jiemin Wong; Karen E Knudsen Journal: Proc Natl Acad Sci U S A Date: 2006-02-06 Impact factor: 11.205