title: Phenotype and polyp landscape in serrated polyposis syndrome:  a series of 100 patients from genetics clinics.
abstract: Serrated polyposis syndrome (SPS), also known as hyperplastic polyposis, is a syndrome of unknown genetic basis defined by the occurrence of multiple serrated polyps in the large intestine and associated with an increased risk of colorectal cancer (CRC). There are a variety of SPS presentations, which may encompass a continuum of phenotypes modified by environmental and genetic factors. To explore the phenotype of SPS, we recorded the histologic and molecular characteristics of multiple colorectal polyps in patients with SPS recruited between 2000 and 2010 from genetics clinics in Australia, New Zealand, Canada, and the United States. Three specialist gastrointestinal pathologists reviewed the polyps, which they classified into conventional adenomas or serrated polyps, with various subtypes, according to the current World Health Organization criteria. Mutations in BRAF and KRAS and mismatch repair protein expression were determined in a subset of polyps. A total of 100 patients were selected for the study, of whom 58 were female and 42 were male. The total polyp count per patient ranged from 6 to 150 (median 30). The vast majority of patients (89%) had polyposis affecting the entire large intestine. From this cohort, 406 polyps were reviewed. Most of the polyps (83%) were serrated polyps: microvesicular hyperplastic polyps (HP) (n=156), goblet cell HP (n=25), sessile serrated adenoma/polyps (SSA/P) (n=110), SSA/P with cytologic dysplasia (n=28), and traditional serrated adenomas (n=18). A further 69 polyps were conventional adenomas. BRAF mutation was mainly detected in SSA/P with dysplasia (95%), SSA/P (85%), microvesicular HP (76%), and traditional serrated adenoma (54%), whereas KRAS mutation was present mainly in goblet cell HP (50%) and in tubulovillous adenoma (45%). Four of 6 SSA/Ps with high-grade dysplasia showed loss of MLH1/PMS2 expression. CRC was diagnosed in 39 patients who were more often found to have a conventional adenoma compared with patients without CRC (P=0.003). Patients with SPS referred to genetics clinics had a pancolonic disease with a high polyp burden and a high rate of BRAF mutation. The occurrence of CRC was associated with the presence of conventional adenoma.
authors.affiliation: Pathology Queensland, Royal Brisbane and Women's Hospital, Herston, QLD 4006, Australia. c.rosty@uq.edu.au
authors.forename: Christophe
authors.initials: C
authors.lastname: Rosty
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Buchanan
authors.forename: Michael D
authors.initials: MD
authors.lastname: Walsh
authors.forename: Sally-Ann
authors.initials: SA
authors.lastname: Pearson
authors.forename: Erika
authors.initials: E
authors.lastname: Pavluk
authors.forename: Rhiannon J
authors.initials: RJ
authors.lastname: Walters
authors.forename: Mark
authors.initials: M
authors.lastname: Clendenning
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Spring
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.forename: Aung K
authors.initials: AK
authors.lastname: Win
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Kevin
authors.initials: K
authors.lastname: Sweet
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Frankel
authors.forename: Melyssa
authors.initials: M
authors.lastname: Aronson
authors.forename: Steve
authors.initials: S
authors.lastname: Gallinger
authors.forename: Jack
authors.initials: J
authors.lastname: Goldblatt
authors.forename: Sonja
authors.initials: S
authors.lastname: Woodall
authors.forename: Julie
authors.initials: J
authors.lastname: Arnold
authors.forename: Neal I
authors.initials: NI
authors.lastname: Walker
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Jass
authors.forename: Susan
authors.initials: S
authors.lastname: Parry
authors.forename: Joanne P
authors.initials: JP
authors.lastname: Young
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D003082:Colectomy; D003106:Colon / Q000473:pathology*; D003111:Colonic Polyps / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004252:DNA Mutational Analysis; D045643:DNA Repair Enzymes / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D013577:Syndrome; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C117307:KRAS protein, human; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D045643:DNA Repair Enzymes