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We have studied 118 renal cell carcinomas to analyse the expressions of cyclins A and D1 and p21[SUP(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[SUP(waf1/cip1)]were not expressed in normal renal tissue. Staining signals of cyclin D1 and p21[SUP(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[SUP(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 ≤ 0.006 for all). The expression of cyclin D1 was linked with age over 65 years, low nuclear grade and high p53 expression (P ≤ 0.05 for all). An inverse correlation was present between p21[SUP(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[SUP(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... [ABSTRACT FROM AUTHOR]

Normally functioning cell-cell adhesion plays an important role in the maintenance of tissue architecture and cell cohesion. E-cadherin is an important adhesion molecule of epithelial cells. In many types of cancer the expression of E-cadherin is reduced leading to increased risk of disease progression. alpha-Catenin is one of the intracellular elements of the E-cadherin-catenin complex. The abnormalities in the expression of alpha-catenin seem to associate with malignant cellular features and disease progression in prostate cancer. To further analyse the significance of alpha-catenin expression, we studied 215 cases of prostate cancer by immunohistochemistry and the results were related to other known prognostic factors and patient survival during a mean follow-up period of 13 years. alpha-Catenin expression was down-regulated in 19% of the cases and 3% of the tumours were totally alpha-catenin-negative. The abnormal alpha-catenin expression and cytoplasmic signal were significantly linked with high T-category, metastatic disease, high Gleason score, perineural growth, high mitotic rate, high S phase fraction and DNA aneuploidy (P < 0.05 for all). In the survival analysis, reduced alpha-catenin expression (P = 0.06) and cytoplasmic signal (P = 0.04) were related to unfavourable patient outcome. In the multivariate analysis, including TM-classification and Gleason score, alpha-catenin expression had independent prognostic value in T1-2 M0 tumors. In the M0 tumours, abnormal alpha-catenin signal was independently associated with recurrence-free survival as well. The results indicate that down-regulation of alpha-catenin is related to several malignant cellular features, and it seems to have prognostic significance in the early phases of cancer progression. We suggest that alpha-catenin expression can provide prognostic information in early prostate cancer.