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Originally published online as doi:10.2353/ajpath.2008.080250 on November 6, 2008

Published online before print November 6, 2008
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(American Journal of Pathology. 2008;173:1853-1860.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.080250

Genomic Biomarkers to Improve Ulcerative Colitis Neoplasia Surveillance

Mary P. Bronner*, Jacintha N. O'Sullivan{dagger}, Peter S. Rabinovitch{ddagger}, David A. Crispin{ddagger}, Lu Chen§, Mary J. Emond, Cyrus E. Rubin|| and Teresa A. Brentnall||

From the Department of Anatomic Pathology,* Cleveland Clinic, Cleveland, Ohio; the Departments of Pathology,{ddagger} Medicine in the Division of Gastroenterology,|| and Biostatistics, University of Washington, Seattle, Washington; the Department of Preventive Medicine,§ University of Southern California, Los Angeles California; and the Education and Research Centre,{dagger} Centre for Colorectal Disease, St. Vincent’s University Hospital, Dublin, Ireland

No adequate means exist to identify the minority of ulcerative colitis (UC) patients destined to undergo neoplastic progression. Recognition of this subset would advance UC cancer surveillance by focusing the available management options onto the highest risk patients. Three different assays of genomic alterations in nondysplastic UC biopsies show promise for distinguishing patients with neoplasia (UC progressors) from those without (UC nonprogressors), including assays of telomere length, anaphase bridges, and chromosomal fluorescence in situ hybridization. Expanding the number of patients and testing of assays simultaneously in the same biopsy further validated their utility. A panel approach also improved testing outcome. A total of 14 UC progressors was readily separable from 15 UC nonprogressors and 6 normal controls. Chromosomal entropy (ie, the extent of alteration diversity) proved to be the most useful test. By receiver-operating characteristic analysis, mean chromosomal entropy in 28 patients over all four chromosomes yielded 100% sensitivity and 92% specificity for distinguishing progressors from nonprogressors with optimum choice of threshold. Moreover, separation was achieved using only nondysplastic and predominantly rectal (82.8%) biopsies that were remote from neoplasia, suggesting that full colonoscopy with extensive biopsies might be avoided for the majority of UC patients, the nonprogressors. These data further strengthen the concept that genomic biomarkers can distinguish UC progressors from nonprogressors and improve cancer surveillance in UC.






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