VEGFR2 Signaling in Intestinal Epithelial Cells Drives Development of Colitis-Associated Colon Cancer

Abstract

with ploidy status and the effect of ploidy status on survival in patients with CRC-IBD are not well defined. Aim: To evaluate the association between DNA content in colon adenocarcinoma cells and clinicohistological risk factors as well as survival in patients with CRC-IBD. Method: Ploidy status of colon adenocarcinoma cells in 50 patients with CRCIBD (44 CRC in ulcerative colitis, 6 CRC in Crohn`s colitis) selected by matching the Norwegian Cancer Registry with IBD cohorts of three university hospitals in Oslo was measured by high-resolution image cytometry. Clinicohistological factors as previously described in this cohort were included. The association of clinicohistological factors and ploidy status were analyzed by non-parametric tests (Mann-Whitney) and the effect of ploidy status on survival by an adjusted Cox regression model. Results: 18/50 (36 %) patients with CRC-IBD showed euploid (13 diploid, 5 tetraploid) and 32/50 (64%) patients aneuploid tumors. Fifteen patients died of CRC related causes, four patients of CRC unrelated causes, four of unknown cause and 27 patients were alive at the end of the study. Adjusted for age at diagnosis of CRC and stage of CRC (stage 1,2,3 versus stage 4), patients with aneuploid CRC showed poorer overall survival compared to patients with euploid CRC (OR=3.275, 95%CI: 1.07-10.04, p=0.038), and, as a tendency, poorer CRC-specific survival (OR=3.252, 95%CI: 0.86-12.27,p=0.082).Median age at diagnosis of IBDwas higher in euploid compared to aneuploid CRC-IBD patients (30y and 24y, respectively, p=0.045). Duration and type of IBD, active colonic inflammation and extent of inflammation at diagnosis of CRC, medication (5ASA compounds), concomitant primary sclerosing cholangitis, localization of the tumor in the colon (right versus left), the extent of neoplasia in the colon (multifocal versus unifocal), type and differentiation grade of adenocarcinomas were not associated with ploidy status, nor did they influence the effect of the ploidy status on survival. Conclusion: DNA content in colon adenocarcinomas measured by image cytometry is an independent predictor of prognosis in patients with CRC-IBD in our cohort. Patients with aneuploid CRC-IBD showed poorer survival than patients with diploid CRC. We could not identify clinical or histological risk factors for aneuploid CRC in our material.