Lynch syndrome (LS) is one of the most common genetic cancer syndromes, occurring at a rate of 1 per 250-1000 in the general population. This autosomal dominant disease is caused by a germline variant in one of the four mismatch repair genes, MSH2, MLH1, MSH6, PMS2, or the EPCAM gene. LS develops at early ages in colorectal cancer (CRC), endometrial cancer, and various other associated tumors. Accurate diagnosis of LS and utilization of various risk-reduction strategies such as surveillance, prophylactic surgery, and chemoprevention could improve clinical outcomes. The efficacy of surveillance has only been proven for CRC; however, specialists have proposed surveillance for other LS associated tumors. Universal screening for tumor tissue using microsatellite instability testing or the mismatch repair protein immunochemistry in all CRC or endometrial cancers is recommended not only as a diagnostic tool for LS, but also as a predictive, prognostic, and therapeutic marker. Next-generation sequencing methods have revealed several conditions with phenotypes similar to LS, such as Lynch-like syndrome, constitutional mismatch repair deficiency syndrome, and polymerase proofreading-associated polyposis. Distinguishing LS from these similar conditions is clinically important, since clinical management for patients differs according to the conditions. Recently, immune checkpoint inhibitors have been shown to be a promising treatment against mismatch repair-deficient (dMMR) solid tumors. The efficacy of immune-checkpoint inhibitors in LS-associated tumors has been shown to be similar to that in sporadic dMMR tumors. This review discusses current clinical topics related to LS screening, diagnosis, surveillance, and therapy.

中文翻译：

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Lynch综合征的当前临床主题。

林奇综合症（LS）是最常见的遗传癌症综合症之一，在普通人群中每250-1000人中有1人发病。这种常染色体显性疾病是由四个错配修复基因之一MSH2，MLH1，MSH6，PMS2或EPCAM基因中的种系变异引起的。LS早在大肠癌（CRC），子宫内膜癌和其他各种相关肿瘤中发展。LS的准确诊断和各种风险降低策略的利用，例如监视，预防性手术和化学预防，可改善临床疗效。监视的有效性仅在CRC中得到了证实；但是，专家们建议对其他与LS相关的肿瘤进行监视。建议在所有CRC或子宫内膜癌中使用微卫星不稳定性测试或错配修复蛋白免疫化学方法对肿瘤组织进行通用筛查，不仅建议将其作为LS的诊断工具，而且还应将其作为预测，预后和治疗的标志物。下一代测序方法已经揭示了几种与LS相似的表型，例如林奇综合征，体质错配修复缺陷综合征和聚合酶校对相关息肉病。从这些相似的疾病中区分出LS在临床上很重要，因为患者的临床管理根据这些疾病而有所不同。最近，免疫检查点抑制剂已被证明是针对错配修复缺陷（dMMR）实体瘤的一种有前途的治疗方法。免疫检查点抑制剂在LS相关肿瘤中的功效已显示与散发dMMR肿瘤相似。这篇综述讨论了与LS筛查，诊断，监测和治疗有关的当前临床主题。