Relationship of Colorectal Adenoma Recurrence to Stem-Like Cell Populations in Crypt Epithelium and Adenomas.
Angela N Bartley, Patricia Thompson, Julie A Buckmeier, Denise J Roe, Chiu-Hsieh Hsu, Peter Lance, Stanley R Hamilton. The University of Texas MD Anderson Cancer Center, Houston; University of Arizona, Tucson
Background: Metachronous development, termed recurrence, of colorectal adenomas after polypectomy is a target for prevention strategies. Markers for adenoma recurrence are needed to identify patients with risk of progression to cancer. Colorectal epithelial stem cells in the near-basal region of crypts are the source of the crypt column, and stem-like cells are known to occur in neoplasms. We characterized the population of crypt stem cells in non-neoplastic mucosa for their possible role in the field defect responsible for adenoma recurrence, and stem-like cells in adenomas as a potential marker for metachronous development.
Design: An initial exploratory coded set of 11 non-neoplastic mucosal biopsy specimens and 20 baseline tubular adenoma (TA) polypectomy specimens was selected from patients with and without recurrence in a Phase III prevention trial. Expression of the stem cell marker aldehyde dehydrogenase-1 (ALDH1) was evaluated by immunohistochemistry, and morphometry was used to enumerate stem-like cells in crypt columns and adenomas. An additional 95 coded adenomas from 82 patients were then analyzed for ALDH1 expression using image analysis with a quantitative nuclear algorithm, and logistic regression analysis was performed.
Results: No differences in stem cell populations were found between the non-neoplastic mucosa of patients with and without adenoma recurrence. However, TAs had higher ALDH1 indices in patients with recurrence than those without recurrence in the exploratory set (53.8% vs. 11.9%, p=.002, for deep glands; 34.5% vs. 6.7%, p=.001, for middle glands; 8.2% vs. 2.1%, p=.03, for surface epithelium). In the larger set of specimens, ALDH1 indices in TAs of patients with recurrence (n=45) were statistically significantly higher than in the 37 patients without recurrence (21.6% vs. 15.2%, p=0.03; OR 1.04, 95%CI= 1.00, 1.08).
Conclusions: We report for the first time the association between higher percentages of stem-like cells in baseline colorectal adenomas and the development of metachronous adenomas. These findings suggest that a larger stem-like cell population in a baseline adenoma may be a marker for propensity of patients to develop a recurrent adenoma. Understanding of the factors inducing stem-like cells in adenomas may lead to mechanism-based prevention strategies.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 29, Wednesday Morning