Lynch综合征（LS）是一种遗传性癌症易感综合征，与结直肠和子宫内膜癌的风险明显增加相关。目前的标准做法是利用多步筛查方案（MSP）对新诊断出的结直肠或子宫内膜癌患者进行LS的普查筛查。然而，MSP可能无法总是准确识别LS病例。为了克服这个限制，我们比较了高危群体中立即遗传物系测序（IGS）与MSP的诊断表现。31名台湾女性患有异步或同步的子宫内膜和结直肠恶性肿瘤，接受了MSP，其中包括DNA错配修复（MMR）蛋白的免疫组织化学染色、MLH1启动子高甲基化分析和遗传物系测序以识别致病变异体。所有在MSP排除的患者均接受了MMR基因的遗传物系测序以模拟IGS用于LS的检测。我们的研究发现，IGS在诊断收益（29.0％对19.4％）和敏感性（90％对60％）方面胜过MSP。具体而言，IGS成功识别了九个LS病例，比MSP检测到的数量多了50％。此外，遗传性甲基化分析还发现了一个MLH1启动子高甲基化的LS病例，使总的LS病例数达到十例（32.3％）。有趣的是，在我们的研究中观察到LS患者与非LS患者在临床特征或总生存率方面没有显著差异。我们的研究表明，在高危患者中，IGS可能比MSP在识别LS方面提供了更有效的方法。这种优势在患者已通过特定的临床标准进行了预选的情况下更为明显。© 2024. 亚洲妇科肿瘤学会，韩国妇产科学会，和日本妇产科学会。

Lynch syndrome (LS) is a hereditary cancer predisposition syndrome with a significantly increased risk of colorectal and endometrial cancers. Current standard practice involves universal screening for LS in patients with newly diagnosed colorectal or endometrial cancer using a multi-step screening protocol (MSP). However, MSP may not always accurately identify LS cases. To address this limitation, we compared the diagnostic performance of immediate germline sequencing (IGS) with MSP in a high-risk group.A total of 31 Taiwanese women with synchronous or metachronous endometrial and colorectal malignancies underwent MSP which included immunohistochemical staining of DNA mismatch repair (MMR) proteins, MLH1 promoter hypermethylation analysis, and germline sequencing to identify pathogenic variants. All patients who were excluded during MSP received germline sequencing for MMR genes to simulate IGS for the detection of LS.Our findings indicate that IGS surpassed MSP in terms of diagnostic yield (29.0% vs. 19.4%, respectively) and sensitivity (90% vs. 60%, respectively). Specifically, IGS successfully identified nine LS cases, which is 50% more than the number detected through MSP. Additionally, germline methylation analysis revealed one more LS case with constitutional MLH1 promoter hypermethylation, bringing the total LS cases to ten (32.3%). Intriguingly, we observed no significant differences in clinical characteristics or overall survival between patients with and without LS in our cohort.Our study suggests that IGS may potentially offer a more effective approach compared to MSP in identifying LS among high-risk patients. This advantage is evident when patients have been pre-selected utilizing specific clinical criteria.© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.