Expression of cyclins A and D and p21((waf1/cip1)) proteins in renal cell cancer and their relation to clinicopathological variables and patient survival

We have studied 118 renal cell carcinomas to analyse the expressions of cyc lins 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 express ed 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 r elated to venous invasion, high nuclear grade, high mitotic rate, high Ki-6 7 and high PCNA expressions (P less than or equal to 0.006 for all). The ex pression of cyclin D1 was linked with age over 65 years, low nuclear grade and high p53 expression (P less than or equal to 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 = 0.00 27) tumours (P = 0.0007). Cyclin D1 and p21((waf1/cip1)), were not signific antly related to survival or disease-free survival in any of the groups. In the entire material the independent prognostic factors were the presence o f 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 express ion (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 independ ent prognostic factor in all clinical stages of the disease, whereas cyclin D1 and p21((waf1/cip1)) have no prognostic value.