Molecular Correlates with “Corkscrew” and Microglandular Architecture in Colorectal Adenomas
AN Bartley, JA Buckmeier, P Thompson, P Lance, SR Hamilton. The University of Texas MD. Anderson Cancer Center, Houston, TX; University of Arizona, Tucson, AZ
Background: The classification of polyps of the colorectum is important; particularly the differences in the histopathologic and molecular characteristics of advanced adenomas and serrated polyps relative to subsequent development of colorectal adenocarcinoma. We evaluated the molecular characteristics of a subset of conventional adenomas with “corkscrew” or microglandular budding architecture.
Design: Adenomas with an infolded corkscrew glandular pattern or microglandular budding were selected from 3500 participants in a phase III chemoprevention trial. Areas of tubular adenoma within the same polyps and separate conventional tubular adenomas (TA), traditional serrated adenomas (TSA), and adjacent and separate non-neoplastic mucosa were selected as controls. Sixty-eight polyps from 56 patients were studied, including 40 adenomas with corkscrew or microglandular budding architecture, six TSA, and 22 conventional TA. Polyps ranged from 3 to 32 mm (mean 14.7 mm, SD 6.9). Histopathologic characteristics also included dilated glands with mucinous epithelium, dystrophic goblet cells, and gastric foveolar-type epithelium. Expression of p53, caspase-3 apoptosis marker, Ki-67, beta-catenin with membranous, cytoplasmic and nuclear localization, and MLH1, MSH2, MSH6, and PMS2 mismatch repair gene products were evaluated by immunohistochemistry in the pre-selected histopathologic regions.
Results: There were significant differences among subtypes of polyps for expression of p53, MLH1, and beta-catenin among the markers evaluated. p53 expression was significantly greater in the corkscrew and microglandular budding areas than in mucosa (p<.006), and in microglandular budding as compared to TSA (p<.03). MLH1 expression was greater in corkscrew areas than in mucosa (p=.04), but less in microglandular budding and dilated glands with mucinous epithelium than in TSA (p=.02). Membranous beta-catenin expression was lower in corkscrew areas than in TSA (p=.05), and cytoplasmic beta-catenin was slightly greater in corkscrew areas than in mucosa (p=.05).
Conclusions: Corkscrew configuration and microglandular budding in conventional adenomas are associated with altered expression of p53 and MLH1 and compartmental localization of beta-catenin. These differences suggest divergence in key molecular progression pathways within conventional adenomas that influence glandular architecture.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 114, Tuesday Morning