Abstract：
MMR gene germline mutations are considered a major genetic disorder in patients with hereditary nonpolyposis colon cancer (HNPCC) or Lynch syndrome; A total of 15% of sporadic colon carcinomas are MSI-High. MSI has also been observed in other cancers, such as endometrial, gastric, and ovarian cancer. The aim of the current study was to correlate and outline the optimal method between the molecular testing of the instability of microsatellite DNA regions (MSI status) and the loss of protein expression by immunehistochemistry (MMR). A total of 242 paraffin-embedded tissues from gastrointestinal, gynecological, genitourinary, lung, breast, and unknown primary cancer patients were analyzed for the expression of MLH1/MSH2/MSH6/PMS2 by immunohistochemistry, as well as for the molecular analysis of MSI status using PCR-based molecular fragment analysis. A total of 29 MSI-High patients were detected molecularly, while 23 patients were detected by immunohistochemistry, with rates that are comparable according to the literature. Based on the agreement coefficient of the two methods, a substantial agreement emerged (Kappa = 0.675 with standard error = 0.081, p < 0.001). Despite the substantial agreement, both methods ought to be established to determine MSI-H/dMMR status in all cancer types as a first-line screening test.
摘要：
MMR基因种系突变被认为是遗传性非息肉病结肠癌（HNPCC）或Lynch综合征患者的主要遗传疾病；散发性结肠癌中总共有15％是MSI-High。在其他癌症中也观察到MSI，如子宫内膜，胃,和卵巢癌。当前研究的目的是关联并概述微卫星DNA区域不稳定性（MSI状态）的分子测试与通过免疫组织化学（MMR）丢失蛋白质表达之间的最佳方法。共有242个石蜡包埋的组织来自胃肠道，妇科,泌尿生殖系统,肺，乳房,和未知原发癌患者通过免疫组织化学分析MLH1/MSH2/MSH6/PMS2的表达，以及使用基于PCR的分子片段分析对MSI状态进行分子分析。共29例MSI-High患者进行了分子检测，而23例患者通过免疫组织化学检测，根据文献，费率是可比的。根据两种方法的一致系数，出现了实质性的一致性(Kappa=0.675，标准误差=0.081，p<0.001)。尽管达成了实质性协议，应该建立两种方法来确定所有癌症类型的MSI-H/dMMR状态,作为一线筛查试验.
