β-catenin expression, DNA ploidy and clinicopathological features in ovarian cancer: A study in 253 patients

Abstract

The CTNNB1 gene and its product β-catenin, a regulator of the Wnt signalling pathway, is often mutated and deregulated in human malignancies. Down stream targets of the Wnt signalling pathway are linked to genomic instability. In this study, the impact of β-catenin expression on genomic instability in ovarian carcinoma, as determined by DNA ploidy, was investigated. Expression of β-catenin was examined by immunohistochemistry in 253 ovarian carcinomas. The results were related to genomic instability and clinicopathological features of the patients. Membrane associated staining of β-catenin was detected in nearly all cases with no correlation to clinical parameters. Most of the samples also had cytoplasmic (84%), while only 13% had nuclear β-catenin localisation. A significant association between β-catenin expression (cytoplasmic and nuclear) and histological subtype and degree of differentiation was observed. Nuclear β-catenin was almost exclusively present in endometroid carcinomas. 53% of all endometroid tumours were positive for nuclear β-catenin expression ( P < 0.0001). Mucinous carcinomas had the highest degree of cytoplasmic β-catenin expression (92%), followed by endometroid (92%), mixed (90%), serous (82%), unclassified adenocarcinomas (81%), carcinomas clear cell and (70%), ( P = 0.01). Tumours with differentiation grade 1 (16%) and 2 (24%) had higher nuclear β-catenin expression than grade 3 and clear cell carcinomas (6%) ( P = 0.012). Better prognostic outcome was found for patients with nuclear β-catenin localisation as compared to the cases without ( P = 0.027). In conclusion, the study showed no correlation between β-catenin expression in ovarian carcinoma and FIGO stage and genomic instability as determined by DNA ploidy status. However, nuclear β-catenin expression was strongly associated with endometroid histological subtype. Finally, in ovarian cancer, although β-catenin staining seems to be of prognostic importance with respect to nuclear staining in univariate analysis, only DNA ploidy status, histological grade and FIGO staging were of independent prognostic significance in multivariate analysis.