title: TP53 gene mutations and p53 protein immunoreactivity in malignant and premalignant Barrett's esophagus.
abstract: OBJECTIVE
  Limited data are available regarding TP53 gene alterations in Barrett's esophagus. This study was undertaken to characterize TP53 mutations and p53 protein immunoreactivity in cancers and preinvasive lesions of Barrett's esophageal mucosa.
  
  
  METHODS
  Seventeen Barrett's adenocarcinomas were examined by polymerase chain reaction amplification, denaturant gradient gel electrophoresis, and sequencing for the presence of TP53 mutations in exons 5-8. In 9 cases, Barrett's epithelium adjacent to the cancer was investigated. p53 protein immunoreactivity was studied with PAb 1801.
  
  
  RESULTS
  Sixteen mutations were found in 15 adenocarcinomas, including 10 missense, 3 nonsense, 1 frameshift, and 2 mutations located within consensus splice donor and acceptor sequences. All nucleotide substitutions were transitions. Eight of the 12 transitions involving a GC base pair occurred within the context of a CpG dinucleotide. p53 immunostaining was present in all 10 cases with missense mutations and in 1 case without a detectable mutation. The surrounding Barrett's mucosa showed TP53 mutations identical to that observed in the carcinoma in only 3 of 5 specimens showing high-grade dysplasia.
  
  
  CONCLUSIONS
  TP53 gene mutations and p53 protein immunostaining are present in a majority of Barrett's adenocarcinomas. Our results suggest that these mutations are involved at an early stage during malignant transformation of Barrett's esophagus.
authors.affiliation: Laboratoire de Génétique des Tumeurs, Institut Curie, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Hamelin
authors.forename: J F
authors.initials: JF
authors.lastname: Fléjou
authors.forename: F
authors.initials: F
authors.lastname: Muzeau
authors.forename: F
authors.initials: F
authors.lastname: Potet
authors.forename: P
authors.initials: P
authors.lastname: Laurent-Puig
authors.forename: F
authors.initials: F
authors.lastname: Fékété
authors.forename: G
authors.initials: G
authors.lastname: Thomas
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D004938:Esophageal Neoplasms / Q000378:metabolism; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000502:physiology; D009154:Mutation; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D013194:Staining and Labeling; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53