Department of Pathology, Landspitali University Hospital of Iceland, Reykjavik, Iceland.
Department of Internal Medicine, Landspitali University Hospital of Iceland, Reykjavik, Iceland.
Genet Med. 2022 May;24(5):999-1007. doi: 10.1016/j.gim.2022.01.012. Epub 2022 Feb 13.
Universal screening for Lynch syndrome (LS) on resected colorectal carcinomas (CRCs) and endometrial carcinomas (ECs) was implemented in Iceland in 2017 using immunohistochemistry (IHC) for mismatch repair (MMR) proteins. We examined the efficacy of the universal screening algorithm to detect LS and the diagnostic accuracy of MMR IHC by comparing results with a population-based genotype database.
All patients diagnosed with CRC or EC per the Icelandic Cancer Registry from 2017 to 2019 who had tumor MMR IHC performed were included. Pathology reports and patient charts were reviewed. MMR IHC stains were crossmatched with genotyping results obtained from the deCODE database.
IHC staining was done on 404 patients with CRC and 74 patients with EC. A total of 61 (15.1%) patients with CRC and 15 (20.3%) patients with EC were MMR-deficient. MMR IHC had 88.9% sensitivity in identifying patients with LS and a positive predictive value of 10.7%. Only 50% of individuals were appropriately referred for genetic testing, leading to underdiagnosis of LS.
Universal screening for LS using MMR protein IHC in CRC and EC accurately identified patients appropriate for genetic testing in a population with MSH6 and PMS2 LS predominance. Because of lack of referral to genetic counseling, only 50% of patients with LS were identified through the screening algorithm.
2017 年，冰岛通过免疫组织化学（IHC）检测错配修复（MMR）蛋白，对结直肠癌（CRC）和子宫内膜癌（EC）患者实施林奇综合征（LS）的广泛筛查。我们通过将免疫组化结果与基于人群的基因数据库进行比较，来评估该通用筛查算法检测 LS 的效果和 MMR IHC 的诊断准确性。
纳入 2017 年至 2019 年期间根据冰岛癌症登记处诊断为 CRC 或 EC 且进行肿瘤 MMR IHC 的所有患者。回顾病理报告和患者病历。将 MMR IHC 染色与 deCODE 数据库中获得的基因分型结果进行交叉匹配。
对 404 例 CRC 患者和 74 例 EC 患者进行了 IHC 染色。共有 61 例（15.1%）CRC 患者和 15 例（20.3%）EC 患者 MMR 缺失。MMR IHC 检测 LS 的敏感度为 88.9%，阳性预测值为 10.7%。仅有 50%的患者被适当转介进行基因检测，导致 LS 漏诊。
在 MSH6 和 PMS2 LS 占主导地位的人群中，CRC 和 EC 中使用 MMR 蛋白 IHC 进行 LS 的广泛筛查可以准确识别适合基因检测的患者。由于缺乏转介至遗传咨询，只有 50%的 LS 患者通过筛查算法被识别。
