Acid suppression therapy may not alter malignant progression in Barrett's metaplasia showing p53 protein accumulation.
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.
Carlson
Nicole
N
Department of Pathology and Medicine, Baylor College of Medicine, Methodist Hospital, Houston, Texas 77030, USA.
Lechago
Juan
J
Richter
Joel
J
Sampliner
Richard E
RE
Peterson
Leif
L
Santella
Regina M
RM
Goldblum
John R
JR
Falk
Gary W
GW
Ertan
Atilla
A
Younes
Mamoun
M
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*
D016159:Tumor Suppressor Protein p53; D004247:DNA