Sfakianaki Maria, Tzardi Maria, Tsantaki Konstantina, Koutoulaki Chara, Messaritakis Ippokratis, Datseri Galateia, Moustou Eleni, Mavroudis Dimitrios, Souglakos John
Laboratory of Translational Oncology, School of Medicine, University of Crete, 71003 Heraklion, Greece.
Department of Pathology, University General Hospital of Heraklion, 71110 Heraklion, Greece.
Cancers (Basel). 2023 Jan 5;15(2):353. doi: 10.3390/cancers15020353.
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.
MMR基因种系突变被认为是遗传性非息肉病性结直肠癌（HNPCC）或林奇综合征患者的一种主要遗传疾病；散发性结肠癌中共有15%为微卫星高度不稳定（MSI-High）。在其他癌症中也观察到了MSI，如子宫内膜癌、胃癌和卵巢癌。本研究的目的是关联并概述微卫星DNA区域不稳定性的分子检测（MSI状态）与免疫组织化学检测的蛋白质表达缺失（MMR）之间的最佳方法。对来自胃肠道、妇科、泌尿生殖系统、肺、乳腺及原发癌不明患者的242份石蜡包埋组织进行免疫组织化学分析，检测MLH1/MSH2/MSH6/PMS2的表达，并使用基于聚合酶链反应（PCR）的分子片段分析对MSI状态进行分子分析。分子检测共发现29例MSI-High患者，免疫组织化学检测发现23例，根据文献，两者的检出率相当。基于两种方法的一致性系数，出现了高度一致性（Kappa = 0.675，标准误差 = 0.081，p < 0.001）。尽管一致性很高，但两种方法都应确立为所有癌症类型中确定MSI-H/dMMR状态的一线筛查检测方法。
