Identification of histologically distinct conventional adenomas that arise predominately in patients with sessile serrated adenomas.
We have recently shown that a study population of patients with at least 1 sessile serrated adenoma (SSA) are 4 times more likely to harbor synchronous serrated polyps [SSAs, traditional serrated adenomas (TSAs) and right sided hyperplastic polyps] than a unselected population of patients. However, 35% of the polyps in the study patients were conventional adenomas (CAds). We hypothesized that the CAds in these study patients would have histologic and molecular differences compared with CAds from a control population without sessile serrated adenomas. To this end, 104 study and 79 control CAds were analyzed according to 9 histologic criteria. A subset of these polyps was also screened for BRAF mutations, KRAS mutations, CpG island methylation, and MUC6 expression. A total of 31 study CAds and 2 control CAds had atypical histologic features (bright cytoplasmic eosinophilia +/- focal serrations and crypt dilatation). None of the adenomas tested had mutations in BRAF or KRAS. Evidence of low levels of CpG island methylation was seen in 35% of the atypical CAds and in only 4.5% of the typical CAds. In addition, these atypical CAds were more likely to express MUC6. Thus, the presence of cytoplasmic eosinophilia with or without focal serrations and crypt dilatation identifies a subset of CAds with characteristics of the serrated neoplasia pathway. These atypical CAds occur more commonly in patients predisposed to developing SSAs and suggest the presence of a mucosal field defect in these patients.
Pai
Rish K
RK
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110-1093, USA. rpai@path.wustl.edu
Mackinnon
Alexander Craig
AC
Joseph
Loren
L
Noffsinger
Amy
A
Hart
John
J
D000236:Adenoma / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000473:pathology*; D000368:Aged; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000473:pathology*; D003111:Colonic Polyps / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000473:pathology*; D018899:CpG Islands; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004108:Dilatation, Pathologic; D004802:Eosinophilia / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055272:Mucin-6 / Q000032:analysis; D009154:Mutation; D011230:Precancerous Conditions / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
C117307:KRAS protein, human; C524734:MUC6 protein, human; D055272:Mucin-6; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins