title: Molecular differences between sporadic serrated and conventional colorectal adenomas.
abstract: OBJECTIVE
  The purpose is to compare the molecular characteristics of serrated adenomas (SAs) with those of conventional adenomas (CADs) and hyperplastic polyps (HPs).
  
  
  METHODS
  We evaluated the proliferative activity and molecular alterations in 47 SAs (25 pure-type and 22 mixed-type), 71 CADs, and 23 HPs.
  
  
  RESULTS
  The proliferative activity of SAs, as evaluated by Ki-67 expression, was intermediate between CADs and HPs. There was no significant difference in the incidence of KRAS or p53 mutations between the three histological groups. In the microsatellite instability (MSI) analysis, 21% of SAs (9 of 43) showed MSI at two or more loci (MSI-H); corresponding values were 5% of CADs (3 of 64) and 8% of HPs (1 of 13; SAs versus CADs, P = 0.0125). MSI-H was more likely to be found in pure-type SAs (36%; 8 of 22) than in mixed-type SAs (5%; 1 of 21; P = 0.0212). Loss of hMLH-1 expression was found in 8 of 9 SAs with MSI-H. The incidence of BRAF or KRAS mutations was 36 and 15% of SAs, respectively; the combined incidence of BRAF and KRAS mutations occurred in 49% of SAs. However, there was no significant difference in the incidence of BRAF or KRAS mutations between SAs with and without MSI-H.
  
  
  CONCLUSIONS
  Genetic instability is more frequently implicated in the tumorigenesis of SAs, especially pure-type SAs, than in that of CADs. In contrast, activation of the Ras/Raf/MEK/MAP kinase cascade by BRAF or KRAS mutation, independently of the genetic instability, may be associated with the progression of about half of SAs.
authors.affiliation: Second Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan. konishigi@hotmail.com
authors.forename: Kazuo
authors.initials: K
authors.lastname: Konishi
authors.forename: Toshiko
authors.initials: T
authors.lastname: Yamochi
authors.forename: Reiko
authors.initials: R
authors.lastname: Makino
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kaneko
authors.forename: Taikan
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Hisako
authors.initials: H
authors.lastname: Nozawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Katagiri
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ito
authors.forename: Kentarou
authors.initials: K
authors.lastname: Nakayama
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ota
authors.forename: Keiji
authors.initials: K
authors.lastname: Mitamura
authors.forename: Michio
authors.initials: M
authors.lastname: Imawari
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf; D000070957:MutL Protein Homolog 1