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The aim of the study is to assess the value of carbonic anhydrase isozyme IX (CA IX) expression as a predictor of disease-free survival (DFS) and disease-specific survival (DSS) in rectal cancer treated by preoperative radio- or chemoradiotherapy or surgery only. Archival tumour samples from 166 patients were analysed for CA IX expression by three different evaluations: positive/negative, proportion of positivity and staining intensity. The results of immunohistochemical analysis were confirmed by demonstrating CA IX protein in western blotting analysis. Forty-four percent of the operative samples were CA IX positive, of these 34% had weak and 66% moderate/strong staining intensity. In univariate survival analysis, intensity of CA IX expression was a predictor of DFS (P=0.003) and DSS (P=0.034), both being markedly longer in tumours with negative or weakly positive staining. In multivariate Cox model, number of metastatic lymph nodes and CA IX intensity were the only independent predictors of DFS. Carbonic anhydrase isozyme IX intensity was the only independent predictor of DSS, with HR=9.2 for dying of disease with moderate-intense CA IX expression as compared with CA IX-negative/weak cases. Negative/weak CA IX staining intensity is an independent predictor of longer DFS and DSS in rectal cancer. [ABSTRACT FROM AUTHOR]

The 52-kDa activator protein (AP)-2 is a DNA-binding transcription factor which has been reported to have growth inhibitory effects in cancer cell lines and in human tumours. In this study the expression of AP-2α was analysed in 303 epithelial ovarian carcinomas by immunohistochemistry (IHC) with a polyclonal AP-2α antibody and its mRNA status was determined by in situ hybridization (ISH) and reverse transcriptase-polymerase chain reaction (RT-PCR). The immunohistochemical expression of AP-2α was correlated with clinicopathological variables, p21/WAF1 protein expression and survival. In normal ovaries, epithelial cells expressed AP-2α protein only in the cytoplasm. In carcinomas nuclear AP-2α expression was observed in 28% of the cases although cytoplasmic expression was more common (51%). The expression of AP-2α varied according to the histological subtype and differentiation. AP-2α and p21/WAF1 expressions did not correlate with each other. Both in univariate (P = 0.002) and multivariate analyses (relative risks (RR) 1.6, 95% confidence interval (CI) 1.13-2.18, P = 0.007) the high cytoplasmic AP-2α expression favoured the overall survival. In contrast, the nuclear AP-2α expression combined with low cytoplasmic expression increased the risk of dying of ovarian cancer (RR = 2.10, 95% CI 1.13-3.83,P = 0.018). The shift in the expression pattern of AP-2α (nuclear vs cytoplasmic) in carcinomas points out to the possibility that this transcription factor may be used by oncogenes in certain histological subtypes. Based on the mRNA analyses, the incomplete expression and translation of AP-2α in ovarian cancer may be due to post-transcriptional regulation. [ABSTRACT FROM AUTHOR]

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]