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Chromosomal and Microsatellite Instability of Adenocarcinomas and Dysplastic Lesions (DALM) in Ulcerative Colitis

van Dieren, Jolanda M. MD*; Wink, Josiane C. MT; Vissers, Kees J. MT; van Marion, Ronald MT; Hoogmans, Monique M.C.P. MT; Dinjens, Winand N.M. PhD; Schouten, W. Ruud MD, PhD; Tanke, Hans J. PhD§; Szuhai, Karoly PhD§; Kuipers, Ernst J. MD PhD*; van der Woude, C. Janneke MD, PhD*; van Dekken, Herman MD, PhD

Diagnostic Molecular Pathology: December 2006 - Volume 15 - Issue 4 - pp 216-222
doi: 10.1097/01.pdm.0000213470.92925.18
Original Articles
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Longstanding ulcerative colitis (UC) is associated with a high risk of developing UC-related colonic adenocarcinoma (UCC). These carcinomas originate from nonadenomatous dysplastic regions referred to as dysplasia associated lesion or mass (DALM). We evaluated chromosomal and microsatellite instability (MSI) in 21 DALM/UCCs. Chromosomal instability was determined by high-resolution array comparative genomic hybridization with a 3500-element BAC-PAC array. MSI was assessed with markers BAT25 and BAT26 and by immunohistochemical analysis of mismatch repair genes. Comparative genomic hybridization revealed frequent losses of array clones (>20% of tumors) at chromosome arms 4p, 5q, and 18q, frequent gains of array clones (>20% of tumors) were found at 1q, 5p, 6p, 7p, 7q, 8p, 8q, 11p, 11q, 12q, 14q, 17q, 19q, 20p, and 20q. The pattern of alterations is dominated by gains on 5p and 20q with loss of 4p, all of which were already present in a patient with carcinoma in situ. Immunohistochemical analysis of mismatch repair genes MLH1, PMS2, MSH2, and MSH6 showed negative immunostaining in 1 neoplasm (5%). MSI of BAT25 and BAT26 was seen in 3 tumors (14%) including the neoplasm with aberrant immunostaining. In conclusion, we constructed a genomic profile of DALM/UCC including several novel genetic alterations. Further, we found a low percentage of MSI. Thus, DALM/UCCs display profound chromosomal instability, but this is not associated with concurrent MSI.

Departments of *Gastroenterology and Hepatology

Pathology

Surgery, Erasmus Medical Center, Rotterdam

§Laboratory of Cytochemistry and Cytometry, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands

Reprints: Herman van Dekken, MD, Department of Pathology, Erasmus MC, University Medical Center Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands (e-mail: h.vandekken@erasmusmc.nl).

Received for publication August 4, 2006; accepted September 6, 2006

© 2006 Lippincott Williams & Wilkins, Inc.