胃黏膜异型增生组织中微卫星不稳定性的检测及其意义的探讨  

Microsatellite instability in dysplasia mucosa and gastric cancer

作　　者：刘平[1] 张小勇[1] 邵耘[1] 赵志泉[1] 

机构地区：[1]南京医科大学第一附属医院消化科,江苏省南京市210029

出　　处：《世界华人消化杂志》2004年第3期512-515,共4页World Chinese Journal of Digestology

基　　金：江苏省科委社会发展基金资助项目.No.BS98028~~

摘　　要：目的:胃黏膜异型增生是胃癌的癌前病变,胃癌的发生可能是胃黏膜异型增生过程中的一系列基因变异累积引起胃黏膜细胞发生恶性转化所致.微卫星不稳定性(MSI)是DNA 基因组不稳定的重要标志,研究胃癌和癌前病变组织MSI 的存在情况,有助于从基因组不稳定的角度探讨胃癌可能的发生机制以及MSI在胃癌发生过程中的可能作用. 方法:胃癌30例、异型增生组织30例分别提取病变组织及相应正常组织的DNA,应用银染:PCR-SSCP技术检测5个微卫星位点不稳定性的存在状况. 结果:胃癌组织MSI的发生率23.3%,胃窦癌MSI的发生率显著高于贲门癌(10%vs 3.3%,P=0.044).胃黏膜异型增生组织的MSI发生率30%,MSI与异型增生的程度无明显关系. 结论:MSI是胃癌多步骤发生过程中的早期分子事件,对胃癌的发生和发展可能具有重要作用.AIM: Gastric mucosa dysplasia has been regarded as a precancerous lesion of the stomach. Abnormal gene alterations in the mucosa dysplasia of the stomach, which may lead to cell transformation, are probably of great importance in the development of gastric cancer (GC). Microsatellite instability (MSI) is a good marker of genome instability. Investigation of MSI in the cancer and precancerous lesion of the stomach will help us to search into the carcinogenesis of stomach and the potential role of MSI in the development of gastric cancer. METHODS: Silver staining single strand conformation polymorphis-polymerease chain reaction (PCR-SSCP) was used to screen MSI markers at 5 loci in formalin-fixed, paraffin-embeded tissues of GC (n =30), dysplasia (n =30) and corresponding normal gastric tissues. RESULTS: The abnormal shifting of the single-strand DNA was identified in 7 (23.3%) out of GC, in 9 (30%) out of dysplasia samples respectively. Three (10%) tumors and two (6.7%) dysplasia displayed a high-level of MSI (two or more loci altered). Low-level MSI (one loci altered) was detected in 13.3% of the tumors and in 23.3% dysplasia samples. GC with MSI was associated with distal location of the tumors (P =0.044). No association was detected between MSI and the grade of dysplasia. CONCLUSION: The accumulation of MSI in the dysplasia of gastric mucosa may be an early molecular event in the development of gastric cancer. It contributes probably to the multistep gastric carcinogenesis.

关 键 词：胃黏膜异型增生 微卫星不稳定性 胃癌 癌前病变 PCR-SSCP技术 

分 类 号：R573[医药卫生—消化系统]