title: Acid suppression therapy may not alter malignant progression in Barrett's metaplasia showing p53 protein accumulation.
abstract: OBJECTIVE
  Several previous studies have shown that malignant progression in Barrett's metaplasia (BM) occurs even in patients treated with fundoplication or acid suppression therapy (AST). The aim of this study was to test the hypothesis that AST may not alter malignant progression in BM if key genes involved in DNA repair and cell cycle control, particularly p53, are defective.
  
  
  METHODS
  Initial and follow-up biopsies from 21 patients with BM treated with AST and observed for 1-13 yr were entered in the study. All biopsies were graded for dysplasia and evaluated for p53 protein accumulation and oxidative DNA damage by immunohiostochemistry, using antibodies to p53 and to 8-hydroxydeoxyguanosine, respectively. DNA ploidy was determined using image analysis. Statistical analysis was performed using Kaplan-Meier curves, log rank test, and multivariate regression.
  
  
  RESULTS
  Patients with p53 positive initial biopsies were more likely to have progression in dysplasia grade (p = 0.022) and DNA ploidy status (p = 0.023) than those with p53 negative biopsies. In eight patients AST resulted in significant reduction in oxidative DNA damage in the five patients with p53-negative initial biopsies, but not the three with p53 positive ones (p = 0.0007).
  
  
  CONCLUSIONS
  We conclude that failure of AST to alter malignant progression in BM may be due, at least in part, to defects in DNA repair and cell cycle control resulting from p53 gene mutation, present before AST treatment. Although AST may be effective in preventing further DNA damage, it is unlikely to alter progression in genetically unstable cells.
authors.affiliation: Department of Pathology and Medicine, Baylor College of Medicine, Methodist Hospital, Houston, Texas 77030, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Carlson
authors.forename: Juan
authors.initials: J
authors.lastname: Lechago
authors.forename: Joel
authors.initials: J
authors.lastname: Richter
authors.forename: Richard E
authors.initials: RE
authors.lastname: Sampliner
authors.forename: Leif
authors.initials: L
authors.lastname: Peterson
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
authors.forename: John R
authors.initials: JR
authors.lastname: Goldblum
authors.forename: Gary W
authors.initials: GW
authors.lastname: Falk
authors.forename: Atilla
authors.initials: A
authors.lastname: Ertan
authors.forename: Mamoun
authors.initials: M
authors.lastname: Younes
mesh_terms: D001471:Barrett Esophagus / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001706:Biopsy; D004247:DNA / Q000235:genetics; D018450:Disease Progression; D004947:Esophagus / Q000473:pathology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D006801:Humans; D008297:Male; D008679:Metaplasia; D011003:Ploidies; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D004247:DNA