Acid suppression therapy may not alter malignant progression in Barrett's metaplasia showing p53 protein accumulation
Acid suppression therapy may not alter malignant progression in Barrett's metaplasia showing p53 protein accumulation
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DOI：
10.1016/s0002-9270(02)04126-6
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发表时间：
2002-06-01
影响因子：
9.8
通讯作者：
Younes, M
中科院分区：
文献类型：
--
作者：
Carlson, N;Lechago, J;Younes, M
目的：先前的几项研究表明，即使在接受胃底折叠术或抑酸治疗（AST）的患者中，Barrett化生（BM）也会发生恶性进展。本研究的目的是测试的假设，AST可能不会改变恶性进展的BM，如果参与DNA修复和细胞周期控制的关键基因，特别是p53，是deficient.METHODS：初始和后续活检21例BM用AST治疗，观察1-13年进入研究。所有的活检组织进行了分级的异型增生和评估p53蛋白的积累和氧化DNA损伤的免疫组织化学，使用抗体p53和8-羟基脱氧鸟苷，分别。使用图像分析确定DNA倍性。统计分析采用Kaplan-Meier曲线，对数秩检验和多元regulation.Results：p53阳性的初始活检患者更有可能有进展的异型增生等级（p = 0.022）和DNA倍体状态（p = 0.023）比那些p53阴性活检。在8名患者中，AST导致5名p53阴性初始活检患者的氧化DNA损伤显著减少，但对3名p53阳性患者没有影响（p = 0.0007）。结论：我们得出结论，AST未能改变BM的恶性进展可能至少部分是由于p53基因突变导致的DNA修复和细胞周期控制缺陷，在AST治疗前存在。虽然AST可能有效地防止进一步的DNA损伤，但它不太可能改变遗传不稳定细胞的进展。
OBJECTIVES: 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.