Original Article

Modern Pathology (2008) 21, 660–669; doi:10.1038/modpathol.2008.55; published online 21 March 2008

Selective expression of gastric mucin MUC6 in colonic sessile serrated adenoma but not in hyperplastic polyp aids in morphological diagnosis of serrated polyps

Scott R Owens1, Simion I Chiosea1 and Shih-Fan Kuan1

1Department of Pathology, Gastrointestinal Pathology Center of Excellence, The University of Pittsburgh Medical Center, Pittsburgh, PA, USA

Correspondence: SR Owens, MD, Department of Pathology, University of Pittsburgh, A610.1 Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA, 15213, USA. E-mail: owenssr@upmc.edu

Received 24 November 2007; Revised 11 February 2008; Accepted 11 February 2008; Published online 21 March 2008.

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Abstract

Colonic sessile serrated adenoma, in contrast to hyperplastic polyp, is thought to be related to sporadic colorectal cancers with high microsatellite instability. However, the morphological distinction between these entities is difficult and subject to observer and sampling variation. Therefore, we elected to investigate the expression of gastric mucin MUC6 as a potential marker to separate the two in the hope of finding an objective and reproducible adjunct to morphological diagnosis. Endoscopic biopsies of colonic polyps with serrated architecture, but without cytological dysplasia were studied and categorized as sessile serrated adenoma or hyperplastic polyp, using previously published morphological criteria. Smaller groups of serrated polyps with cytological dysplasia (traditional serrated adenomas, filiform serrated adenomas and sessile serrated adenomas with cytological dysplasia) were also included. In total, 94 polyps were immunohistochemically stained with antibodies to MUC6 and to MLH-1. MUC6 was found to have 100% specificity in distinguishing sessile serrated adenoma (N=26; positive staining) from hyperplastic polyp (N=48; negative staining). Traditional serrated adenomas and filiform serrated adenomas were also negative for MUC6. Sessile serrated adenomas with cytological dysplasia were found to lose expression of MLH-1 in dysplastic areas, while retaining MUC6 expression. Neither anatomic location in the right or left colon nor polyp size appears to account for the differences in MUC6 expression.

Keywords:

sessile serrated adenoma, hyperplastic polyp, serrated neoplasia pathway, microsatellite instability, MUC6

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