Department of Pathology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu 520-2192, Japan.
Cancer Lett. 2010 Nov 28;297(2):244-51. doi: 10.1016/j.canlet.2010.05.017. Epub 2010 Jun 17.
Microsatellite instability (MSI) is known to result from inactivation of mismatch repair genes largely by promoter methylation. However, the methylation usually accumulates time-dependently. To know whether MSI can be acquired later in tumorigenesis, we examined intratumoral heterogeneity of MSI and promoter methylation of hMLH1 after immunohistochemical screening for heterogeneous expression of hMLH1 in 55 cases of gastric carcinomas. We demonstrated for the first time that MSI-H can develop from MSI-L or the absence of MSI due to time-dependent accumulation of DNA methylation during progression of early-stage gastric carcinomas. The resultant replication errors may play a role in enhancing invasive activity.
微卫星不稳定（MSI）已知是由于错配修复基因的失活引起的，主要是通过启动子甲基化。然而，甲基化通常是随时间积累的。为了了解 MSI 是否可以在肿瘤发生的后期获得，我们在 55 例胃癌病例中免疫组织化学筛选 hMLH1 的异质表达后，检查了 MSI 和 hMLH1 启动子甲基化的肿瘤内异质性。我们首次证明，MSI-H 可以从 MSI-L 或由于早期胃癌进展过程中 DNA 甲基化的时间依赖性积累而导致的 MSI 缺失发展而来。由此产生的复制错误可能在增强侵袭活性中起作用。
