Elucidation of the mechanisms involved in development and suppression ofBarrett's esophagus: Results of joint Japan-U.S. research

我们评估了几种分子改变，包括微卫星不稳定性（MSI）; hMLH 1，p16，E-cadherin和APC基因的CpG岛甲基化状态;和单克隆抗体Das-1，其特异性地与BE在特化肠化生（SIM），以及在柱状内衬上皮（CLE）没有SIM在BE粘膜。此外，我们在一项随机对照试验中研究了上述分子标志物的变化，比较了PPI给药组与PPI非给药组。我们的研究结果表明，在SIM或CLE中研究的任何基因的MSI或甲基化频率没有显著差异。相比之下，Das-1反应性在SIM中显著高于CLE。日本人中甲基化和Das-1反应性的频率与美国人群中BE的频率相似，这一发现证实了以前的报告。PPI组、MSI组和p16基因高甲基化组的E-cadherin和APC基因在干预后消失，而未PPI组则无此趋势。这些结果表明，CLE可能是一种癌前病变，以及SIM，并有没有日本和美国之间的BE的分子特征的差异。此外，PPI可促进BE中涉及的分子改变的消退。

We evaluated several molecular alterations including microsatellite instability (MSI); the CpG island methylation status of hMLH1, p16, E-cadherin and APC genes; and monoclonal antibody Das-1, which specifically reacts with BE in specialized intestinal metaplasia (SIM), as well as in columnar lined epithelium (CLE) without SIM in BE mucosa. Additionally, we investigated changes in the above molecular markers in a randomized control trial, comparing PPI administration versus PPI non-administration groups. Our results showed no significant differences in the frequency of MSI, or methylation at any genes investigated in SIM or CLE. In contrast, Das-1 reactivity was significantly higher in SIM versus CLE. The frequency of methylation and Das-1 reactivity among Japanese was similar to that of BE in the U.S. population, a finding which corroborates previous reports. In patients administered PPI, MSI and hypermethylation at p16, E-cadherin, and APC genes disappeared following interventon, while patients without PPI did not show this tendency. These results indicate that CLE may be a precancerous lesion as well as SIM, and there is no difference in the molecular characteristics of BE between Japanese and U.S. populations. Furthermore, PPI may promote regression of the molecular alterations involved in BE.