Expression of non-membranous beta-catenin and gamma-catenin, c-Myc and cyclin D1 in relation to patient outcome in human colon adenocarcinomas.

Non-membranous beta-catenin and gamma-catenin, c-Myc and cyclin D1 are key participants in the Wnt cell signalling pathway, in which aberrancies have been associated with malignant cell transformation. We assessed the independent prognostic value of these proteins in a clinical material. Tumours from a series of 162 patients operated on for Dukes' stage A, B and C colonic adenocarcinomas were analysed using semiquantitative immunohistochemistry and the results were related to patient outcome. Patients expressing nuclear beta-catenin in the primary tumour showed reduced survival compared to other patients (log rank p=0.028) and there was also an association with development of metastases follow-up (logistic regression p=0.024). Using multivariate analysis (Cox regression) co-expression of nuclear beta-catenin and c-Myc turned out to be the strongest marker of impaired prognosis (p=0.001, HR 5.26, 95% CI 1.93-14.36). Expression of non-membranous gamma-catenin, cyclin D1 and c-Myc alone failed to have independent prognostic significance in our study.