TY - JOUR
T1 - Expression of gastric pyloric mucin, MUC6, in colorectal serrated polyps
AU - Bartley, Angela N.
AU - Thompson, Patricia A.
AU - Buckmeier, Julie A.
AU - Kepler, Carole Y.
AU - Hsu, Chiu Hsieh
AU - Snyder, Manuel S.
AU - Lance, Peter
AU - Bhattacharyya, Achyut
AU - Hamilton, Stanley R.
N1 - Funding Information:
We thank Dr Ray Nagle and staff for carrying out the immunostaining for this project, and Kim-Anh Vu for color figures. This work was supported by National Cancer Institute grant CA-41108. Immunohistochemical data were generated by the TAC-MASS Core (Tissue Acquisition and Cellular/ Molecular Analysis Shared Service) that is supported by the Arizona Cancer Center Support Grant, NIH CA023074.
Funding Information:
Dr Hamilton is supported by the Frederick F. Becker Distinguished University Chair for Cancer Research.
PY - 2010/2
Y1 - 2010/2
N2 - Serrated polyps of the colorectal mucosa represent a heterogeneous and controversial taxonomic category with variation in histopathological, molecular, and immunohistochemical characteristics and with an incomplete understanding of pathogenesis. A previous study reported that the expression of gastric pyloric-type mucin, MUC6, characterized sessile serrated adenomas. We therefore evaluated the expression of MUC6 in serrated polyps identified among 2502 participants in a Phase III chemoprevention trial within the Arizona Cancer Center Colorectal Cancer Prevention Trials Program and characterized the associated histopathological features and location. We carried out 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. In all 92 hyperplastic polyps, 43 sessile serrated adenomas, and 11 traditional serrated adenomas were included. Polyps ranged in size from 1-150 mm. 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. A total of 53% of sessile serrated adenomas (n23), 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. The extent of positive staining ranged from 2-100% of crypt cells and was independent of the histopathological 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 only has modest utility as a tissue biomarker for sessile serrated adenoma.
AB - Serrated polyps of the colorectal mucosa represent a heterogeneous and controversial taxonomic category with variation in histopathological, molecular, and immunohistochemical characteristics and with an incomplete understanding of pathogenesis. A previous study reported that the expression of gastric pyloric-type mucin, MUC6, characterized sessile serrated adenomas. We therefore evaluated the expression of MUC6 in serrated polyps identified among 2502 participants in a Phase III chemoprevention trial within the Arizona Cancer Center Colorectal Cancer Prevention Trials Program and characterized the associated histopathological features and location. We carried out 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. In all 92 hyperplastic polyps, 43 sessile serrated adenomas, and 11 traditional serrated adenomas were included. Polyps ranged in size from 1-150 mm. 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. A total of 53% of sessile serrated adenomas (n23), 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. The extent of positive staining ranged from 2-100% of crypt cells and was independent of the histopathological 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 only has modest utility as a tissue biomarker for sessile serrated adenoma.
KW - Colonic neoplasm
KW - Hyperplastic polyp
KW - MUC6
KW - Serrated adenoma
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U2 - 10.1038/modpathol.2009.155
DO - 10.1038/modpathol.2009.155
M3 - Article
C2 - 19855374
AN - SCOPUS:76349109035
SN - 0893-3952
VL - 23
SP - 169
EP - 176
JO - Modern Pathology
JF - Modern Pathology
IS - 2
ER -