Carcinoma in Crohn's Disease: Mucinous Histology Is Not Associated with Microsatellite Instability or Mismatch Repair Protein Deficiency.
Andrea Grin, Paul Ryan, Aaron Pollett, Robert Riddell. St. Michael's Hospital, Toronto, Canada; Bon Secours Hospital, Cork, Ireland; Mount Sinai Hospital, Toronto, Canada; University of Toronto, ON, Canada
Background: The risk of malignancy in Crohn's disease (CD) depends on disease duration, severity and extent. The proportion of tumors with morphology and molecular features of microsatellite instability which may have better stage for stage outcome has not been described in such patients. We retrospectively reviewed gastrointestinal malignancies occurring in CD patients from the records of a tertiary referral centre for these features.
Design: Only tumors occurring in bowel sites known to be involved by CD were included. Clinicopathological characteristics were recorded and the tumor was tested for immunohistochemical expression of mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) and for microsatellite instability (MSI) at 2 loci (BAT25, BAT26).
Results: 21 tumors in 20 patients were identified (17 resections, 4 biopsies), with equal gender distribution at a median age of 52.0 yrs (range 31-85 yrs). Only 2 tumors occurred in small bowel, and 3 in the right colon. The remainder were all in the sigmoid colon or rectum (11) within sigmoidoscopic range, but 6 occurred in anal fistula tracts. Mucinous predominant (7) or partial differentiation (5) occurred in 60%, with other features suggestive of MSI seen in an additional 2 cases. Of 17 cases available for testing, all 4 MMR proteins were intact and tumors were microsatellite stable in 8 of 10 (80%) cases with and 6 of 7 (86%) cases without MSI-type features. The other 3 tumors were MLH1 and PMS2 deficient and were MSI-high.
Conclusions: Carcinoma complicating CD occurs in younger patients, most commonly in the distal large bowel, and often shows MSI-type features, but usually without concomitant loss of mismatch repair genes or MSI. The relative paucity of small bowel tumors may reflect surgery before malignancy occurs, or may reflect a major change in the distribution of carcinoma in CD.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 41, Wednesday Morning