Sporadic Microsatellite Instability-High Colon Cancers Rarely Display Immunohistochemical Evidence of Wnt Signaling Activation. (March 2015)

• Record Type: Journal Article
• Authors: Panarelli, Nicole C.; Vaughn, Cecily P.; Samowitz, Wade S.; Yantiss, Rhonda K.
• Is Part Of: American journal of surgical pathology. Volume 39:Number 3(2015)
• Publication Date: 2015-03
• Subjects: Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000000380
• Languages: English
• ISSNs: 0147-5185

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>Most sporadic colonic adenocarcinomas are microsatellite stable (MSS) and arise from conventional adenomas by dysregulation of the APC/β-catenin/Wnt signaling pathway. Sporadic adenocarcinomas with a high degree of microsatellite instability (MSI) likely arise from sessile serrated polyps through the serrated neoplastic pathway. These polyps contain <italic>BRAF</italic> mutations and are prone to epigenetic methylation that ultimately silences <italic>MLH1</italic>, leading to MSI and heralding progression of dysplasia to invasive adenocarcinoma. Most investigators believe that these 2 models of cancer progression are mutually exclusive, although recent studies describe Wnt signaling activation in serrated polyps and propose that it plays a role in the development of sporadic colonic adenocarcinomas with MSI. We sought to test this hypothesis by evaluating β-catenin immunoexpression in 44 sporadic microsatellite unstable adenocarcinomas and 44 MSS colon cancers. We defined sporadic MSI-high carcinomas as those with loss of MLH1 and PMS2 immunostaining and <italic>BRAF</italic> V600E mutations that occurred in patients 50 years of age or older without a family history of colonic adenocarcinoma or Lynch syndrome. Forty-one (93%) of these carcinomas displayed membranous β-catenin staining only, compared with 28 (64%) site-matched MSS tumors with abnormal nuclear β-catenin staining.</p> </sec> </abstract>