title: p53 and K-ras status in duodenal adenomas in familial adenomatous polyposis.
abstract: BACKGROUND
  The genetic alterations in patients with familial adenomatous polyposis (FAP) and duodenal adenomas are poorly characterized when compared with data relating to colorectal tumorigenesis in the same patients.
  
  
  METHODS
  Point mutation of the K-ras oncogene and point mutation and overexpression of the TP53 tumour suppressor gene were investigated in 32 duodenal polyps (seven without mucosal pathology, 23 with mildly dysplastic adenomas and two with moderately dysplastic adenomas) from 21 patients with FAP.
  
  
  RESULTS
  K-ras mutation, TP53 mutation or positive p53 staining were not found in duodenal polyps without histological abnormality. Of 25 duodenal adenomas, K-ras mutation was found in three (two mildly dysplastic, one moderately dysplastic), 20 showed positive p53 immunostaining, and mutation of the TP53 gene was found in one moderately dysplastic adenoma. p53 protein overexpression in duodenal adenomas was significantly more frequent than mutation of either K-ras or TP53 (P < 0.01).
  
  
  CONCLUSIONS
  p53 dysfunction is a hallmark of duodenal adenomas in patients with FAP. Overexpression may indicate DNA damage and thus an early step in tumorigenesis.
authors.affiliation: Polyposis Registry, St Mark's Hospital, Harrow, Middlesex, UK.
authors.forename: H
authors.initials: H
authors.lastname: Kashiwagi
authors.forename: A D
authors.initials: AD
authors.lastname: Spigelman
authors.forename: I C
authors.initials: IC
authors.lastname: Talbot
authors.forename: H S
authors.initials: HS
authors.lastname: Debinski
authors.forename: A B
authors.initials: AB
authors.lastname: McKie
authors.forename: N R
authors.initials: NR
authors.lastname: Lemoine
authors.forename: R K
authors.initials: RK
authors.lastname: Phillips
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D001706:Biopsy; D004379:Duodenal Neoplasms / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction