Expression of Aldehyde Dehydrogenase in Dysplastic Lesions Arising from Inflammatory Bowel Disease.
Adam D Toll, Bruce Boman, Juan P Palazzo. Thomas Jefferson Hospital, Philadelphia; Thomas Jefferson University, Philadelphia
Background: The cancer stem cell hypothesis proposes a relatively small population of neoplastic cells have the unique ability to initiate and sustain tumoral growth. Detection of cancer stem cells has been performed with a variety of markers, most notably aldehyde dehydrogenase (ALDH), responsible for catalyzing the irreversible oxidation of aromatic aldehydes to their corresponding carboxylic acids. Prior work has shown increased ALDH expression in carcinomas is an independent predictor of poor prognosis. We hypothesize cancer stem cells are present in pre-neoplastic lesions as well, and examined this within the context of dysplasia arising from inflammatory bowel disease (IBD). The distinction between inflammatory change and dysplasia can be difficult, and has significant patient management implications. Increasing levels of ALDH may help identify dysplasia, and confirm the role of stem cells in cancer progression.
Design: Fifty-four surgical resections of IBD were studied. All diagnoses were confirmed by at least two experienced pathologists. The diagnostic categories were as follows: 13 high-grade dysplasia / adenocarcinoma, 19 low-grade dysplasia, and 22 inflammatory atypia / negative for dysplasia. Immunohistochemical staining for ALDH was evaluated in the cytoplasm of epithelial cells both on intensity (0-3+), and percentage of cells staining. Criteria for positive staining was modeled after previous work, requiring at least 1+ staining in >10% of cells to be considered positive.
Results: Positive staining was seen in 100% of cases with high-grade dysplasia / adenocarcinoma (13/13), and 95% (18/19) of cases with low-grade dysplasia. Staining was homogeneous in the cytoplasm of dysplastic mucosa. Adjacent benign mucosa showed patchy focal positivity mainly in the crypt base. Staining of invasive adenocarcinoma was strongest in the advancing front. Cases with inflammatory atypia / negative for dysplasia showed positive staining in 32% (7/22) of cases. The sensitivity and specificity of ALDH for dysplasia was 97% and 68%, respectively.
Conclusions: Our study demonstrates ALDH is significantly expressed in dysplastic lesions arising from IBD. ALDH-expression in cancer stem cells suggests an important causative role in the progression to cancer in IBD. Although we found high sensitivity for dysplasia, the specificity was poor. In addition to neoplasia, ALDH-expressing stem cells proliferate in response to chronic inflammation, accounting for the cases of inflammatory atypia with positive ALDH expression.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 25, Wednesday Morning