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

我们评估了一些分子改变，包括微卫星不稳定性(MSI)，hMLH1，p16，E-cadherin和APC基因的CpG岛甲基化状态，以及在特发性肠化生(SIM)中与BE特异反应的单抗Das-1，以及在BE黏膜中没有SIM的柱状衬里上皮(CLE)中。此外，我们在一项随机对照试验中调查了上述分子标志物的变化，比较了PPI给药组和非PPI给药组。我们的结果显示，在SIM或CLE研究的任何基因上，MSI或甲基化的频率没有显著差异。相比之下，SIM组的DAS-1活性显著高于CLE组。日本人的甲基化频率和Das-1活性与美国人群中的BE相似，这一发现证实了之前的报道。在接受PPI、MSI和p16高甲基化的患者中，E-cadherin和APC基因在间隔时间后消失，而没有PPI的患者没有表现出这种趋势。这些结果表明，CLE可能是一种癌前病变，也可能是SIM，并且BE的分子特征在日本和美国人群中没有差异。此外，PPI可能促进BE所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.