Microsatellite instability and loss of mismatch-repair protein expression in gastric carcinoma
- Author:
- No author available
- Journal Title:
- WORLD CHINESE JOURNAL OF DIGESTOLOGY
- Issue:
- 8
- DOI:
- 10.3969/j.issn.1009-3079.2004.08.004
- Key Word:
- No keyword available
Abstract： 目的:分析胃癌组织微卫星不稳定性、错配修复蛋白表达以及二者的关系,探讨胃癌发生的分子生物学机制.方法:胃腺癌及癌旁组织标本56例,高分化癌22例,中低分化癌34例,早期癌20例,中晚期癌36例,常规酚-氯仿法提取DNA,选取基因组上的五个微卫星位点BAT-26、D17S261、D3S1283、D2S123和D3S1611,进行PCR扩增,扩增产物加入GeneScan 500size standard共同热变性后,用60 g/L的SLPA添加8m0l/L尿素做筛分递质的毛细管电泳进行分析.被检测的五个微卫星位点如出现两个或两个以上位点的不稳定,定为微卫星的高度不稳定(MSI-H),一个位点出现不稳定、定为微卫星的低度不稳定(MSI-L),没有位点出现不稳定、定为微卫星稳定(MSS).石蜡切片常规免疫组织化学SP方法检测hMLH1和hMSH2蛋白的表达,肿瘤组织上皮细胞核不着色,而周围组织上皮细胞核着色判定为hMLH1或hMSH2蛋白表达的缺失.结果:在56例胃腺癌中,有14例(25%)表现为MSI-H,14例(25%)有错配修复蛋白表达的缺失.在14例MSI-H的胃癌组织中,11例(79%)有hMLH1或hMSH2表达的缺失,42例MSI-L/MSS的胃癌组织仅3例(7%)有hMLH1或hMSH2表达的缺失.胃癌的MSI-H与错配修复蛋白表达的缺失高度相关(P＜0.01).其中的22例高分化腺癌有7例(32%)表现为MSI-H、6例(27%)有错配修复蛋白表达的缺失,34例中低分化腺癌7例(21%)表现为MSI-H、8例(24%)有错配修复蛋白表达的缺失,20例早期腺癌有1例(5%)表现为MSI-H、3例(15%)有错配修复蛋白表达的缺失,36例中晚期腺癌13例(36%)表现为MSI-H、11例(31%)有错配修复蛋白表达的缺失.微卫星不稳定性在中晚期胃癌明显高于早期胃癌(P＜0.05),但在不同分化程度的胃癌差异不明显;MMR蛋白表达缺失在高分化与低分化以及早期与中晚期的胃癌均无显著性差异.结论:细胞错配修复功能缺陷与部分胃癌的发生有关,而与胃癌的生物学行为无关;胃癌的微卫星不稳定性随着肿瘤的演进而增加.
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