Sporadic microsatellite instability-high colon cancers rarely display immunohistochemical evidence of Wnt signaling activation

Nicole C. Panarelli, Cecily P. Vaughn, Wade S. Samowitz, Rhonda K. Yantiss

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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 BRAF mutations and are prone to epigenetic methylation that ultimately silences MLH1, 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 BRAF 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.

Original languageEnglish (US)
Pages (from-to)313-317
Number of pages5
JournalAmerican Journal of Surgical Pathology
Volume39
Issue number3
DOIs
StatePublished - Feb 28 2015
Externally publishedYes

Keywords

  • APC
  • BRAF
  • serrated neoplastic pathway
  • sessile serrated polyp
  • β-catenin

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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