Dysplastic lesions in inflammatory bowel disease show increased positivity for the stem cell marker aldehyde dehydrogenase

Abstract

The chronic inflammatory state in patients with inflammatory bowel disease places them at a substantially elevated risk for developing colorectal carcinoma. Moreover, distinguishing an inflammatory phenotype from dysplasia in inflammatory bowel disease can be difficult and has significant patient management implications. To this end, we studied the expression of the cancer stem cell marker aldehyde dehydrogenase to determine whether expression is increased in dysplastic lesions arising in inflammatory bowel disease. We studied 54 patients with inflammatory bowel disease who underwent surgical resection. Of the 54 patients, 13 exhibited high-grade dysplasia or adenocarcinoma, 19 exhibited low-grade dysplasia, and 22 displayed only inflammatory atypia. Staining for aldehyde dehydrogenase was evaluated in the cytoplasm of epithelial and stromal cells. We determined the intensity of staining (0 to 3+) and the percentage of cells staining positively. Positive staining for aldehyde dehydrogenase was observed in 92% (12/13) of cases with high-grade dysplasia/adenocarcinoma and in 95% (18/19) of cases with low-grade dysplasia. Cases with inflammatory atypia showed positive staining in 45% (10/22) of cases. The sensitivity for aldehyde dehydrogenase in epithelial cells as a marker for dysplasia was 95%; specificity was 55%. For stromal cells adjacent to dysplasia, sensitivity was 44%; and specificity was 68%. Although the sensitivity of aldehyde dehydrogenase for dysplasia was excellent, specificity was less than ideal. Our findings support the hypothesis that dysplasia in inflammatory bowel disease is associated with increased aldehyde dehydrogenase positivity, which supports the cancer stem cell hypothesis.