Sessile Serrated Polyps are Precursors of Colon Carcinomas With Deficient DNA Mismatch Repair

Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association
Seth SweetserFrank A Sinicrope

Abstract

We investigated whether sessile serrated adenomas/polyps (SSA/Ps) are direct precursors of colorectal carcinomas. We identified colon carcinomas that arose from SSA/Ps among 2646 colorectal cancers included in the surgical pathology database at the Mayo Clinic (2006-2012). Molecular features of the serrated neoplasia pathway were analyzed in these tumors by immunohistochemical analyses of mutant BRAF (V600E) and MLH1 proteins. Among the 33 identified SSA/P-associated colonic adenocarcinomas (median patient age, 75 y), 24 developed in women (73%), 31 were located in the proximal colon (94%), and 23 (69%) were TNM stage I or II. Thirty-one of the tumors (94%) expressed mutant BRAF; of these, 26 also had loss of MLH1 (79%), indicating deficient DNA mismatch repair of sporadic origin. Twenty-two of the tumors (67%) were interval cancers that were more common in women and did not differ significantly in TNM stage, BRAF mutation, or loss of MLH1. By histopathology, SSA/Ps that were associated with colon carcinomas contained frequent dysplasia (48%). Most cancers that arose from SSA/Ps were located on the right side of the colon and had mutant BRAF and loss of MLH1. These findings indicate that SSA/Ps are precursors of most sporadic c...Continue Reading

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Citations

Nov 17, 2016·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Joseph C Anderson, Douglas J Robertson
Jun 3, 2020·International Journal of Molecular Sciences·Rina Fujiwara-TaniHiroki Kuniyasu
Dec 5, 2019·World Journal of Gastrointestinal Oncology·Shui-Ming WangYu Wang
Jul 16, 2017·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Z BaiZ Zhang
Mar 23, 2017·Cancer Prevention Research·Shahrooz RashtakFrank A Sinicrope
Mar 21, 2020·The Lancet. Gastroenterology & Hepatology·Mingyang SongJonas F Ludvigsson
Feb 9, 2021·Endoscopy International Open·Aasma ShaukatWilliam Brugge
Mar 23, 2020·Gastroenterology·Reinier G S MeesterUri Ladabaum

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