Large-scale genomic instability in colon adenocarcinomas and correlation with patient outcome

The purpose of this study was to evaluate the association between DNA content in colon adenocarcinomas using high-resolution image cytometry and patient outcome. Tumours from 219 patients operated for colon adenocarcinoma were analysed using high-resolution image cytometry. Proteins involved in cell cycle propulsion (cyclins A, D1, D3 and E) and cell proliferation (c-Myc and non-membranous beta-catenin) have previously been reported in the same cohort and were included in this study. The results were related to disease-free survival and to cancer-specific death. Patients with aneuploid tumours showed shorter relapse-free survival than patients with euploid tumours (univariate log-rank test, p = 0.004 and multivariate Cox regression model p = 0.009, HR 0.51, 95% CI 0.31-0.84). Also the risk of death from cancer was greater in patients with aneuploid tumours (log-rank test, p = 0.006 multivariate Cox regression model p = 0.014, HR 0.47, 95% CI 0.26-0.86). When analysing patients with Dukes stages A and B, nuclear expression of beta-catenin was highly significantly associated with both shorter relapse-free survival (p < 0.005, HR 5.0, 95% CI 1.6-15.5) and cancer-specific death (p = 0.036, HR 6.9, 95% CI 1.1-42.1). DNA content in colon adenocarcinomas measured by image cytometry is an independent predictor of prognosis in our patients operated for colon adenocarcinoma.