The distribution of chromosomal and microsatellite instability in colorectal cancers related to inflammatory bowel disease.

Abstract

3607 Background: Surveillance for colorectal cancer (CRC) in inflammatory bowel disease (IBD) has so far not been effective. Mucosal or fecal biomarkers may be useful in the selection of high risk patients. The yield may depend on the underlying carcinogenic pathway. In IBD associated CRC (IBD-CRC) the distribution of chromosomal instability (CIN) and microsatellite instability (MSI) is not well documented. Our objective was to determine the distribution of CIN and MSI and the association to clinico-histological factors in a cohort of patients with IBD-CRC. Methods: Ploidy was measured by high-resolution image cytometry and MSI by using two markers (BAT 25 and BAT26) in 62 patients with 72 CRC-IBD selected by matching the Norwegian Cancer Registry with IBD cohorts of three university hospitals in Oslo. The association between ploidy/MSI status and clinicohistological factors were analyzed by non-parametric tests. Results: Ploidy status was analyzed in 67 (93%), microsatellite stability in 68 (94%) tumors. Fourty-nine (73.1%) were non-diploid (43 aneuploid, 1 polyploid, 5 tetraploid), 13 (19.4 %) diploid, five (7.5%) indeterminate. Forty-three (63.2%) were microsatellite stable (MSS), four (5.8%) microsatellite instable (MSI). One tumor was MSI in BAT25 but MSS in BAT26. Twenty (29.5%) tumors showed no PCR-product in at least one of the markers. In 46 tumors, both ploidy and MSI status were available. All non-diploid tumours (36, 78.3%) were MSS and all MSI tumors (4, 8.7%) were diploid. Six (13%) tumors were diploid and MSS. Four patients were treated with 5-ASA prior to diagnosis of CRC. Three developed diploid, one aneuploid cancers. Of the untreated patients, 31 developed aneuploid, 7 diploid cancers (p=0.036). We did not find an association between age, gender, type of IBD, duration of IBD, localisation of CRC,TNM-stage and CIN or MSI. Conclusions: The majority of CRC-IBD in our cohort seem to present CIN and only a minority MSI. Some CRC-IBD patients present neither CIN nor MSI. Future studies should determine whether these display the CpG island methylator phenotype. Biomarkers for CRC-IBD should be derived from all three pathways.