Expression of Gastric Mucin MUC6 in Colonic Serrated Polyps
AN Bartley, PA Thompson, JA Buckmeier, P Lin, CY Kepler, CH Hsu, MP Lance, A Bhattacharyya, SR Hamilton. University of Arizona, Tucson, AZ; The University of Texas MD Anderson Cancer Center, Houston, TX
Background: Serrated lesions of the colon are a heterogeneous category for which consistent application of diagnostic histologic criteria remains challenging. Previous studies have shown variable reproducibility in the distinction of serrated lesions based on molecular and immunohistochemical features. Recently, gastric-type mucin MUC6 expression has been reported to distinguish serrated lesions for improved diagnosis. We compared the expression of MUC6 in proximal and distal serrated polyps.
Design: We identified and described the histologic features and location of serrated lesions obtained from 3792 participants from two large Phase III chemoprevention trials. Immunohistochemistry for MUC6, beta-catenin, p16, hMLH-1, and O-6-methylguanine-DNA methyltransferase (MGMT) were performed on 92 serrated lesions. Distribution of positivity was assessed using percentage expression and a grading scale was used for staining intensity.
Results: Forty-nine hyperplastic polyps (HP), 29 sessile serrated adenomas (SSA), 12 traditional serrated adenomas (TSA), and two mixed lesions (one SSA/HP and one SSA with areas of cytologic dysplasia, SSAD) were included in the study. The mean lesion size was 5mm, ranging from 1-20mm. Seven SSA's (24%), one TSA (8%), and six HPs (12%) were positive for MUC6, but none of the mixed lesions were positive. Immunostaining for MUC6 was limited to the lower crypts in all lesions with the exception of one SSA that had greater staining intensity on the surface. Positive staining of cells in the basal crypts ranged from 5-100% and was independent of histologic type. The difference in MUC6 expression was not significant based on location or size. Beta-catenin expression was primarily cytoplasmic and membranous with no nuclear localization. There was no significant beta-catenin expression differences between the lesions, or glandular versus surface location. Only the SSAD showed loss of hMLH-1. Expression of p16 and MGMT were not significantly different between lesions.
Conclusions: In contrast to previous studies, site-specific or selective expression of MUC6 could not be used to distinguish between serrated adenomas or hyperplastic polyps. No significant differences were found among serrated lesions with regard to loss of hMLH-1, or beta-catenin, p16 or MGMT expression.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 79, Wednesday Morning