title: Sessile serrated adenomas with low- and high-grade dysplasia and early carcinomas: an immunohistochemical study of serrated lesions "caught in the act".
abstract: Sessile serrated adenomas (SSAs) show serrations typical of hyperplastic polyps but display architectural differences and lack traditional dysplasia. SSAs with foci of low- (LGD) or high-grade dysplasia (HGD) or early invasive carcinoma are seldom biopsied and, thus, are not well studied. Immunohistochemical analysis for MLH1, MSH2, MSH6, and PMS2 (mismatch repair gene products) was performed on colon biopsy specimens from 11 patients (age range, 54-87 years; 4 men and 7 women) showing SSA with LGD (n = 1), HGD (n = 5), or focal invasive carcinoma (n = 5). All 11 cases showed intact nuclear staining for MSH2 and MSH6 in the SSA component; in foci of LGD, HGD, or carcinoma; and in background normal mucosa. In contrast, there was tandem loss of MLH1 and PMS2 in zones of LGD (1/1) or HGD (3/5) and early carcinoma (2/4; with concordant loss in associated HGD) but retention in SSA areas (11/11) and normal mucosa (11/11). No patient was known to have hereditary nonpolyposis colorectal cancer/Lynch syndrome. This study offers additional strong evidence that SSA is truly a precursor to at least a subset of sporadic microsatellite-unstable colorectal cancer.
authors.affiliation: Department of Pathology, Johns Hopkins Hospital, Baltimore, MD 21231-2401, USA.
authors.forename: Todd B
authors.initials: TB
authors.lastname: Sheridan
authors.forename: Hubert
authors.initials: H
authors.lastname: Fenton
authors.forename: Marc R
authors.initials: MR
authors.lastname: Lewin
authors.forename: Ashlie L
authors.initials: AL
authors.lastname: Burkart
authors.forename: Christine A
authors.initials: CA
authors.lastname: Iacobuzio-Donahue
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Frankel
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Montgomery
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000236:Adenoma / Q000737:chemistry / Q000473:pathology*; D000251:Adenosine Triphosphatases / Q000032:analysis; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002278:Carcinoma in Situ / Q000737:chemistry / Q000473:pathology*; D002352:Carrier Proteins / Q000032:analysis; D002467:Cell Nucleus / Q000737:chemistry / Q000473:pathology; D003111:Colonic Polyps / Q000737:chemistry / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000473:pathology*; D045643:DNA Repair Enzymes / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D011230:Precancerous Conditions / Q000737:chemistry / Q000473:pathology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes