title: Serrated tubulovillous adenoma of the large intestine.
abstract: OBJECTIVE
  Most colorectal polyps are classified readily, but a subset of tubulovillous adenomas (TVA) with prominent serrated architecture causes diagnostic confusion. We aimed to (i) identify histological features that separate serrated TVAs from both conventional TVAs and traditional serrated adenomas (TSA) and (ii) perform a clinicopathological and molecular analysis to determine if the serrated TVA has unique features.
  
  
  RESULTS
  We collected 48 serrated TVAs, 50 conventional TVAs and 66 BRAF wild-type TSAs for analysis. For each polyp we performed a clinicopathological assessment, BRAF and KRAS mutation profiling, cytosine-phosphate-guanosine (CpG) island methylator phenotype status, MGMT methylation and immunohistochemical assessment of seven markers [MutL homologue 1 (MLH1), p16, p53, β-catenin, Ki67, CK7 and CK20]. We found that serrated TVAs can be diagnosed reliably, and have features distinct from both conventional TVAs and TSAs. Compared to conventional TVAs, serrated TVAs are larger, more often proximal, more histologically advanced, show more CpG island methylation and more frequent KRAS mutation. Compared to TSAs they are more often proximal, show less CpG island methylation, more frequent MGMT methylation and more frequent nuclear staining for β-catenin.
  
  
  CONCLUSIONS
  The serrated TVA can be diagnosed reliably and has unique features. It represents a precursor of KRAS mutated, microsatellite stable colorectal carcinoma.
authors.affiliation: The Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.|School of Medicine, The University of Queensland, Brisbane, QLD, Australia.|Envoi Specialist Pathologists, Brisbane, QLD, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Bettington
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, QLD, Australia.|Envoi Specialist Pathologists, Brisbane, QLD, Australia.
authors.forename: Neal
authors.initials: N
authors.lastname: Walker
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, QLD, Australia.|Envoi Specialist Pathologists, Brisbane, QLD, Australia.|Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Carlton, Vic., Australia.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rosty
authors.affiliation: Envoi Specialist Pathologists, Brisbane, QLD, Australia.|Department of Anatomical Pathology, Pathology Queensland, Brisbane, QLD, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Brown
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, QLD, Australia.|Envoi Specialist Pathologists, Brisbane, QLD, Australia.|Department of Anatomical Pathology, Pathology Queensland, Brisbane, QLD, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Clouston
authors.affiliation: The Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: Diane
authors.initials: D
authors.lastname: McKeone
authors.affiliation: The Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: Sally-Ann
authors.initials: SA
authors.lastname: Pearson
authors.affiliation: Statistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: Kerenaftali
authors.initials: K
authors.lastname: Klein
authors.affiliation: The Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.|School of Medicine, The University of Queensland, Brisbane, QLD, Australia.|The Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Leggett
authors.affiliation: The Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.|School of Medicine, The University of Queensland, Brisbane, QLD, Australia.|Department of Chemical Pathology, Pathology Queensland, Brisbane, QLD, Australia.
authors.forename: Vicki
authors.initials: V
authors.lastname: Whitehall
mesh_terms: D018253:Adenoma, Villous / Q000235:genetics / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor
keywords: adenoma; colonic polyps; serrated; traditional serrated adenoma; tubulovillous adenoma