title: Expression of cyclins A and D and p21(waf1/cip1) proteins in renal cell cancer and their relation to clinicopathological variables and patient survival.
abstract: We have studied 118 renal cell carcinomas to analyse the expressions of cyclins A and D1 and p21(waf1/cip1), and their relationship to clinical and histopathological parameters as well as to clinical outcome. Cyclins A and D1 and cyclin-dependent kinase inhibitor p21 (waf1/cip1) were not expressed in normal renal tissue. Staining signals of cyclin D1 and p21(waf1/cip1) were always nuclear but cyclin A was also expressed in the cytoplasm of the tumour cells. The mean (range) fractions of cyclin A, cyclin D1 and p21(waf1/cip1)-positive tumour cells were 2.2% (range 0-20%), 23.3% (range 0-90%) and 6.8% (range 0-70%) respectively. The expression of cyclin A was related to venous invasion, high nuclear grade, high mitotic rate, high Ki-67 and high PCNA expressions (P < or = 0.006 for all). The expression of cyclin D1 was linked with age over 65 years, low nuclear grade and high p53 expression (P < or = 0.05 for all). An inverse correlation was present between p21(waf1/cip1) and cyclin D1 (P = 0.011). Cyclin A predicted survival in the entire study group (P = 0.0014), in T1-4/N0-2/M0 (P = 0.0007) and in T1-2/N0/M0 tumours (P = 0.0007). Cyclin A was also a powerful predictor of disease-free survival in T1-4/N0/M0 (P = 0.0027) tumours (P = 0.0007). Cyclin D1 and p21(waf1/cip1) were not significantly related to survival or disease-free survival in any of the groups. In the entire material the independent prognostic factors were the presence of distant metastases (relative risk (RR) 5.16, P < 0.001), T category (RR 2.68, P < 0.001), Ki-67 expression (RR 1.02, P = 0.026) and cyclin A expression (RR 1.12, P = 0.001). The independent predictors in T1-4/N0/M0 tumours were T-category (RR 2.67, P = 0.001) and cyclin A (RR 1.21, P < 0.001), and in T1-2/N0/M0 tumours the only significant predictor was cyclin A (RR 1.19, P = 0.0002). In renal cell carcinoma, cyclin A is a powerful and independent prognostic factor in all clinical stages of the disease, whereas cyclin D1 and p21(waf1/cip1) have no prognostic value.
authors.affiliation: Department of Urology, Kuopio University Hospital, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Aaltomaa
authors.forename: P
authors.initials: P
authors.lastname: Lipponen
authors.forename: M
authors.initials: M
authors.lastname: Ala-Opas
authors.forename: M
authors.initials: M
authors.lastname: Eskelinen
authors.forename: K
authors.initials: K
authors.lastname: Syrjänen
authors.forename: V M
authors.initials: VM
authors.lastname: Kosma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D019925:Cyclin A / Q000032:analysis*; D056741:Cyclin D; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis*; D004791:Enzyme Inhibitors / Q000032:analysis; D005500:Follow-Up Studies; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008875:Middle Aged; D008940:Mitotic Index; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D019925:Cyclin A; D056741:Cyclin D; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53