Microsatellite instability in gastric intestinal metaplasia in patients with and without gastric cancer
Microsatellite instability in gastric intestinal metaplasia in patients with and without gastric cancer
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DOI：
10.1016/s0002-9440(10)64758-x
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发表时间：
2000-02-01
影响因子：
6
通讯作者：
Sepulveda, AR
中科院分区：
文献类型：
--
作者：
Leung, WK;Kim, JJ;Sepulveda, AR
微卫星不稳定性（microsatellite instability， MSI）在胃癌发生中的作用和意义尚不清楚。本研究通过检查胃癌患者和非胃癌患者的肠化生（IM）来确定MSI在胃癌发生中的年代学。从75例胃LM患者（30例胃癌，26例消化性溃疡，19例慢性胃炎）的胃标本中提取DNA，并用8个微卫星标记进行扩增。8个（26.7%）肿瘤和7个（9.3%）IM样本（3个来自无癌患者）显示高水平MSI（3个或更多位点改变）。在50%的肿瘤、40%的与癌症共存的IM样本和38%的无癌个体的IM组织中检测到低水平的MSI（一个或两个位点改变）。在30例肿瘤患者中，微卫星在LM合并MSI的肿瘤中发生的频率更高（P = 0.003）。此外，肿瘤组织中MSI水平较低的患者发生活动性幽门螺杆菌感染的可能性高于肿瘤稳定的患者（P = 0.02）。综上所述，本研究表明MSI不仅发生在胃癌患者的胃IM中，也发生在无癌个体的胃IM中。这些数据表明，MSI在IM区域的渐进式积累可能有助于胃癌的发展，代表了多步骤胃癌发生级联中的一个重要分子事件。
The role and significance of microsatellite instability (MSI) in gastric carcinogenesis remain unknown. This study determined the chronology of MSI in gastric carcinogenesis by examining intestinal metaplasia (IM) from patients with and without gastric can cer. DNA was obtained from gastric specimens of 75 patients with gastric LM (30 cancer, 26 peptic ulcer, and 19 chronic gastritis patients) and was amplified with a set of eight microsatellite markers. Eight (26.7%) tumors and seven (9.3%) IM samples (three from cancer-free patients) displayed high-level MSI (three or more loci altered). Low-level MSI (one or two loci altered) was detected in 50% of the tumors, in 40% of IM samples coexisting with cancer, and in 38% of IM tissues of cancer-free individuals. Among the 30 cancer patients, microsatellites were more frequently altered in LM coexisting with tumors that showed MSI (P = 0.003). In addition, patients with low-level MSI in the tumor tissues were more likely to have active Helicobacter pylori infection than those with stable tumors (P = 0.02). In conclusion, this study indicates that MSI occurs not only in gastric IM of patients with gastric carcinoma, but also in IM of cancer-free individuals. These data suggest that the progressive accumulation of MSI in areas of IM may contribute to gastric cancer development, representing an important molecular event in the multistep gastric carcinogenesis cascade.