Purpose: To develop a method for testing the MSI based on targeted NGS. Methods: Based on the results of previous studies, 81 microsatellite loci with high variability in MSI-H tumors were selected, and a method for calculating the MSI score was developed. Using the MSI score, we defined the MSI status in endometral (162), colon (153), and stomach (190) cancers. Accuracy of the MSI scores was evaluated by comparison with MMR immunohistochemistry for 137 endometrium (63 dMMR and 74 pMMR), 76 colon (29 dMMR and 47 pMMR), and 81 stomach (8 dMMR and 73 pMMR) cancers. Results: Classification of MSS and MSI-H tumors was performed with AUC (0.99), sensitivity (92%), and specificity (98%) for all tumors without division into types. The accuracy of MSI testing in endometrial cancer was lower than for stomach and colon cancer (0.98, 87%, and 100%, respectively). The use of 27 loci only, the most informative for endometrial cancer, increased the overall accuracy (1.00, 99%, and 99%). Comparison of MSI score values in 505 tumors showed that MSI score is significantly higher in colon (p< 10−5) and stomach (p= 0.008) cancer compared with endometrial cancer. Conclusion: The MSI score accurately determines MSI status for endometrial, colon, and stomach cancers and can be used to quantify the degree of MSI.
目的：开发一种基于靶向二代测序检测微卫星不稳定的方法。方法：基于前期研究结果，筛选出81个在MSI-H肿瘤中具有高变异性的微卫星位点，并建立微卫星不稳定性评分计算方法。应用该评分系统，我们对子宫内膜癌（162例）、结肠癌（153例）和胃癌（190例）的微卫星不稳定状态进行界定。通过对比137例子宫内膜癌（63例错配修复缺陷型，74例错配修复正常型）、76例结肠癌（29例错配修复缺陷型，47例错配修复正常型）及81例胃癌（8例错配修复缺陷型，73例错配修复正常型）的错配修复蛋白免疫组化检测结果，评估微卫星不稳定性评分的准确性。结果：在不区分肿瘤类型的情况下，微卫星稳定与微卫星高度不稳定肿瘤的区分效能达到曲线下面积0.99、敏感性92%、特异性98%。子宫内膜癌的检测准确性低于胃癌和结肠癌（分别为0.98、87%和100%）。仅使用27个对子宫内膜癌最具鉴别价值的位点可提升整体检测效能（1.00、99%和99%）。对505例肿瘤的微卫星不稳定性评分比较显示，结肠癌（p<10⁻⁵）和胃癌（p=0.008）的评分显著高于子宫内膜癌。结论：微卫星不稳定性评分能准确判定子宫内膜癌、结肠癌和胃癌的微卫星不稳定状态，可用于量化微卫星不稳定程度。
Detecting Microsatellite Instability in Endometrial, Colon, and Stomach Cancers Using Targeted NGS
肿瘤(癌症)患者之家