title: Distinct profile of HIF1α, PTCH, EphB2, or DNA repair protein expression and BRAF mutation in colorectal serrated adenoma.
abstract: OBJECTIVE
  The serrated colorectal carcinoma (CRC) as proposed to arise from serrated adenoma (SA) is characterized by upregulation of HIF1α, suppression of PTCH or EphB2, loss of DNA repair proteins, and BRAF mutation. The aim of this study was to evaluate alterations of these candidates involved in the serrated pathway in colorectal polyps.
  
  
  METHODS
  We analyzed immunoreactivity of these proteins, methylation of PTCH and EphB2, and mutation of BRAF and Kras in sessile SAs (SSAs; n = 32), traditional SAs (n = 28), hyperplastic polyps (HPs; n = 24), and conventional adenomas (ADs; n = 21).
  
  
  RESULTS
  Increase of nuclear HIF1α expression was more frequent in SA than HP, but less frequent in SA than AD (P < 0.001). Increase of PTCH expression was not found in SSA or HP, but was evident in about half of traditional SA and all AD (P < 0.001). Decrease of EphB2 expression was more prominent in SA than HP or AD (P ≤ 0.005). Loss of hMLH1 and MGMT expression were most frequent in SSA (P < 0.001). Loss of hMSH2 showed more pronounced in SA and HP than AD (P ≤ 0.004). Methylations of PTCH and EphB2 were rare in all categories. BRAF mutation harbored frequently in SA, but not AD; only AD harbored Kras mutation.
  
  
  CONCLUSIONS
  This work provides evidence of similarity of HIF1α, EphB2 or DNA repair proteins expression, and BRAF mutation in serrated CRCs and their precursors, especially SSA, compared with AD and HP.
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan; Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Morimoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mitomi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.forename: Michiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Murakami
authors.forename: Naoto
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Yao
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004260:DNA Repair / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008297:Male; D008745:Methylation; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009154:Mutation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D036183:Receptor, EphB2 / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C117307:KRAS protein, human; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; C586310:EPHB2 protein, human; D036183:Receptor, EphB2; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: BRAF; EphB2; HIF1α; PTCH; serrated adenoma