Objectives: The objective of the study is to provide an efficient and practical screening strategy to distinguish a broader spectrum of Lynch syndrome (LS) and LS mimics-associated colorectal cancer (CRC), including Lynch-like syndrome (LLS), constitutional mismatch repair-deficiency, familial CRC type X (FCCTX), and polymerase proofreading-associated polyposis syndrome.
Materials and Methods: 1294 cases of CRC samples were detected mismatch repair (MMR) status using immunohistochemistry (IHC) staining, in which the cases with MLH1-deficient CRC underwent BRAF mutation analysis by IHC. Following the personal and/or family history survey, next-generation sequencing (NGS) was used to detect gene variants.
Results: 1294 CRC patients were dichotomized into tumors caused by a deficient MMR (dMMR) system and a proficient MMR (pMMR) system after MMR status analysis. 45 patients with suspected sporadic dMMR CRC were then separated from MLH1-deficient CRC though BRAF mutation status analysis by IHC. Following the personal and/or family history survey for 1294 patients, as well as germline genetic testing by NGS, 34 patients were diagnosed as LS (8 cases), SLS (13 cases), LLS ( 6 cases), FCCTX (3 cases), and sporadic CRC (4 cases).
Conclusions: Our screening strategy, which consists of clinical and molecular analyses, is expected to improve the screening efficiency and management for the LS and LS mimics.


中文翻译：

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林奇综合征和林奇综合征在结直肠癌中的一种实用筛查策略


目的：本研究的目的是提供一种有效且实用的筛查策略，以区分更广泛的林奇综合征 (LS) 和 LS 模拟相关结直肠癌 (CRC)，包括林奇样综合征 (LLS)、体质错配修复-缺乏，家族性CRC X型（FCCTX）和聚合酶校对相关的息肉病综合征。
材料与方法：采用免疫组织化学（IHC）染色检测1294例CRC样本的错配修复（MMR）状态，其中MLH1缺陷的CRC病例通过IHC进行BRAF突变分析。在个人和/或家族史调查之后，使用下一代测序 (NGS) 检测基因变异。
结果：1294 例 CRC 患者在 MMR 状态分析后被分为由缺陷 MMR (dMMR) 系统和精通 MMR (pMMR) 系统引起的肿瘤。然后通过 IHC 的 BRAF 突变状态分析将 45 名疑似散发性 dMMR CRC 患者与 MLH1 缺陷型 CRC 分开。经对1294例患者的个人和/或家族史调查，以及NGS生殖系基因检测，34例患者被诊断为LS（8例）、SLS（13例）、LLS（6例）、FCCTX（3例）和散发性CRC（4例）。
结论：我们的筛查策略包括临床和分子分析，有望提高 LS 和 LS 模拟物的筛查效率和管理。