title: Morphologic and molecular characterization of traditional serrated adenomas of the distal colon and rectum.
abstract: Of the serrated polyps, the origin, morphologic features, molecular alterations, and natural history of traditional serrated adenomas (TSAs) are the least understood. Recent studies suggest that these polyps may arise from precursor lesions. The frequencies of KRAS and BRAF mutations vary between these studies, and only 1 small study has measured CpG island methylation using current markers of methylation. Mutations in GNAS, a gene commonly mutated in colorectal villous adenomas, have not been fully evaluated in TSAs. Finally, the expression of annexin A10 (ANXA10), a recently discovered marker of sessile serrated adenomas/polyps, has not been studied in these polyps. To further characterize these polyps, 5 gastrointestinal pathologists reviewed 55 left-sided polyps diagnosed as TSA at a single institution. Pathologists assessed various histologic features including cytoplasmic eosinophilia, ectopic crypt foci, presence of conventional dysplasia, and presence of precursor serrated lesions. KRAS, BRAF, and GNAS mutational analysis was performed, as well as CpG island methylation and ANXA10 immunohistochemistry. Ectopic crypt foci were seen in 62% of TSAs. Precursor lesions were seen in 24% of the study polyps, most of which were hyperplastic polyps. KRAS and BRAF mutations were common and were present in 42% and 48% of polyps, respectively. GNAS mutations occurred in 8% of polyps, often in conjunction with a BRAF mutation. Unlike sessile serrated adenomas/polyps, TSAs rarely had diffuse expression of ANXA10. Importantly, BRAF-mutated TSAs had more widespread methylation of a 5-marker CpG island panel compared with KRAS-mutated polyps. However, ectopic crypt foci, a proposed defining feature of TSA, were not associated with any specific molecular alteration.
authors.affiliation: Departments of *Anatomic Pathology †Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH.
authors.forename: Homer O
authors.initials: HO
authors.lastname: Wiland
authors.forename: Bonnie
authors.initials: B
authors.lastname: Shadrach
authors.forename: Daniela
authors.initials: D
authors.lastname: Allende
authors.forename: Paula
authors.initials: P
authors.lastname: Carver
authors.forename: John R
authors.initials: JR
authors.lastname: Goldblum
authors.forename: Xiuli
authors.initials: X
authors.lastname: Liu
authors.forename: Deepa T
authors.initials: DT
authors.lastname: Patil
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Rybicki
authors.forename: Rish K
authors.initials: RK
authors.lastname: Pai
mesh_terms: D000236:Adenoma / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017302:Annexins / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001706:Biopsy; D002864:Chromogranins; D003110:Colonic Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D003111:Colonic Polyps / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009820:Ohio; D010641:Phenotype; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012004:Rectal Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D018631:ras Proteins / Q000235:genetics
chemical_list: C121387:ANXA10 protein, human; D017302:Annexins; D014408:Biomarkers, Tumor; D002864:Chromogranins; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins