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P329. Large scale genomic instability in patients with colorectal cancer in inflammatory bowel disease – Association with clinico­histological factors and survival

S.A. Brackmann1,2, M. Einarsen Pretorius3,4, S. Norheim Andersen5, F. Langmark6, O.P. Fraas Clausen7, M. Vatn1, H. Danielsen3,4

1Department of Clinical Molecular Biology, Institute of Clinical Medicine, Akershus University Hospital, Nordbyhagen, Norway; 2Lovisenberg Diakonale Hospital, Oslo, Norway; 3Institute Medical Informatics, Oslo University Hospital, Oslo, Norway; 4Centre for Cancer Biomedicine, Oslo University Hospital, Oslo, Norway; 5Department of Pathology, Akershus University Hospital, Nordbyhagen, Norway; 6The Cancer Registry of Norway, Oslo, Norway; 7Division of Pathology, Section for Carcinogenesis, Oslo University Hospital, Oslo, Norway

Background: The risk of colorectal cancer (CRC) in inflammatory bowel diseases (IBD) is increased compared to the background population (sporadic CRC). Risk factors for CRC-IBD include clinicohistological factors. DNA content (ploidy status) is an independent riskfactor for survival in patients with sporadic CRC in whom large scale genomic instability (aneuploidy) is associated with poorer prognosis. The association of clinicohistological factors 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 CRC-IBD (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 (MannWhitney) 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 of CRC unrelated causes, four of unknown cause and 27 patients were alive at end of study.

Adjusted for age at CRC diagnosis and stage (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 IBD diagnosis was higher in euploid compared to aneuploid CRC-IBD patients (30 y and 24 y, respectively, p = 0.045).

Age at diagnosis and duration of IBD, IBD type, active and extent of inflammation, medication (5ASA) and concomitant primary sclerosing cholangitis were not associated with ploidy status or survival.

Localization of the tumor in the colon (right, left), the extent of neoplasia in the colon (multifocal, unifocal), type and differentiation of adenocarcinomas were not associated with ploidystatus, 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 clinicalohistological risk factors for aneuploid CRC.