Expression of Gastric Pyloric Mucin MUC6 in Colorectal Serrated Polyps

Serrated polyps of the colorectal mucosa represent a heterogeneous and controversial taxonomic category with variation in histopathologic, molecular, and immunohistochemical characteristics and with incomplete understanding of pathogenesis. A previous study reported that expression of gastric pyloric-type mucin MUC6 characterized sessile serrated adenomas. We therefore evaluated the expression of MUC6 in serrated polyps identified among 2,502 participants in a Phase III chemoprevention trial within the Arizona Cancer Center Colorectal Cancer Prevention Trials Program and characterized the associated histopathologic features and location. We performed immunohistochemistry for MUC6 on 146 serrated lesions and 87 conventional tubular adenomas and assessed the percentage of cells with expression and the grade of staining intensity. Ninety-two hyperplastic polyps, 43 sessile serrated adenomas, and 11 traditional serrated adenomas were included. Polyps ranged in size from 1 to 150 millimeters. The association of MUC6 staining with serrated polyp category was evaluated using classification and regression tree (CART) analysis and two-sided Fisher’s exact test. 53% of sessile serrated adenomas (n=23), 17 % of hyperplastic polyps (n=16), and 18% of traditional serrated adenomas (n=2) but none of 87 tubular adenomas expressed MUC6. Expression was limited to the lower crypts in all serrated polyps. Extent of positive staining ranged from 2–100% of crypt cells and was independent of histopathologic type. MUC6 expression had relatively high specificity for sessile serrated adenoma (82%) but low sensitivity (54%). In CART analysis, proximal location was found to be the best partitioning factor for MUC6, followed by classification as sessile serrated adenoma. We conclude that MUC6 expression is strongly associated with proximal location of serrated polyps but has only modest utility as a tissue biomarker for sessile serrated adenoma.