Colorectal Cancer in Colonic Crohn's Disease - High Frequency of DNA-Aneuploidy

Abstract

Background: The risk of colorectal cancer (CRC) in colonic Crohn's disease (CCD) seems to be of the same magnitude as in extensive, longstanding ulcerative colitis (UC) and colonoscopic surveillance has been advocated. Mucosal dysplasia and DNA-aneuploidy are early warning markers of malignant transformation in UC. Data concerning the occurrence of such premalignant lesions in CCD are scarce. Aims: The objective of this study was to investigate the DNA ploidy pattern in CCD-patients with manifest CRC, both in the tumour, as well as in the adjacent and distant colorectal mucosa. The results from DNA-flow cytometry analyses (FCM) prior to the development of a CRC in CCD were also investigated. Materials and Methods: Biopsies obtained at colonoscopy and surgical specimens from 43 patients with colonic or ileocolonic CD developing CRC between 1988 and 1998 were reviewed. The CRC histological phenotype, and the occurrence of dysplasia were registered. CRC-tissue and tissue from areas with dysplasia adjacent to and/or distant from the tumour were obtained from paraffin-embedded blocks and were analysed by FCM after preparation. Results: Twenty-four CRCs in 21 patients (14 men) were suitable for FCM-analyses. The median age at CRC-diagnosis was 53 years (21-73) and the median CCD-duration was 14.5 years (1-50). A predominance of CRC was found either in the cecum (9/24) or in the rectum (7/24). DNA-aneuploidy was found in 62.5% (15/24) of the tumours, in 25% (2/8) in adjacent and/or distant mucosa, and in 50% (2/4) of the patients that had been subjected to colonoscopic surveillance prior to the CRC-diagnosis. In 7 patients (29%), definite dysplasia was detected adjacent to and/or distant from the tumour. Of the 6 patients undergoing colonoscopic surveillance, 3 (50%) displayed definite dysplasia prior to the colectomy. Conclusion: Since DNA- aneuploidy is a common feature in CRCs in CCD and precede the development of invasive carcinoma, inclusion of FCM-analyses of colorectal biopsies may enhance the sensitivity of identifying high-risk CCD-patients prone to develop CRC within the frame of colonoscopic surveillance programs.