title: Sessile Serrated Polyps are Precursors of Colon Carcinomas With Deficient DNA Mismatch Repair.
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 colon carcinomas with deficient DNA mismatch repair.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Seth
authors.initials: S
authors.lastname: Sweetser
authors.affiliation: Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Andrea
authors.initials: A
authors.lastname: Jones
authors.affiliation: Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Smyrk
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota. Electronic address: sinicrope.frank@mayo.edu.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Sinicrope
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000473:pathology*; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000473:pathology*; D053843:DNA Mismatch Repair; D045643:DNA Repair Enzymes / Q000172:deficiency*; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008853:Microscopy; D008875:Middle Aged; D000070957:MutL Protein Homolog 1 / Q000032:analysis; D011127:Polyps / Q000150:complications* / Q000473:pathology*; D048493:Proto-Oncogene Proteins B-raf / Q000032:analysis
chemical_list: C501486:MLH1 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1; D045643:DNA Repair Enzymes
keywords: Colon Cancer; Genetics; MMR; Progression