Department of Clinical Oncology, Kyoto University Hospital, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto, Kyoto, 606-8507, Japan.
Department of Real World Data Research and Development, Graduate School of Medicine, Kyoto University, 54 Shogoin-kawara-cho, Sakyo-ku, Kyoto, Japan.
Int J Clin Oncol. 2024 Nov;29(11):1696-1703. doi: 10.1007/s10147-024-02609-w. Epub 2024 Aug 26.
Lynch syndrome (LS) is a hereditary cancer syndrome caused by pathogenic germline variants in mismatch repair (MMR) genes, which predisposes to various types of cancers showing deficient MMR (dMMR). Identification of LS probands is crucial to reduce cancer-related deaths in affected families. Although universal screening is recommended for colorectal and endometrial cancers, and age-restricted screening is proposed as an alternative, LS screening covering a broader spectrum of cancer types is needed. In the current study, we elucidated the rate of dMMR tumors and evaluated the outcome of LS screening in young-onset extra-colorectal LS-associated cancers.
Immunohistochemistry for MMR proteins were retrospectively performed in a total of 309 tissue samples of endometrial, non-mucinous ovarian, gastric, urothelial, pancreatic, biliary tract, and adrenal cancers in patients < 50 years of age. Clinicopathological information and the results of genetic testing were obtained from medical charts.
There were 24 dMMR tumors (7.8%) including 18 endometrial, three ovarian, two urothelial, and one gastric cancer. Co-occurrence of colorectal cancer and family history of LS-associated cancers was significantly enriched in patients with dMMR tumors. Among the 16 patients with dMMR tumors who were informed of the immunohistochemistry results, five with endometrial and one with urothelial cancer were diagnosed as LS with positive pathogenic variants in MMR genes.
We report the outcome of immunohistochemistry for MMR proteins performed in multiple types of young-onset extra-colorectal LS-associated cancers. Our study demonstrates the feasibility of a comprehensive LS screening program incorporating young-onset patients with various types of extra-colorectal LS-associated cancers.
林奇综合征（LS）是一种遗传性癌症综合征，由错配修复（MMR）基因的致病性种系变异引起，易患各种表现出 MMR 缺陷（dMMR）的癌症。LS 先证者的识别对于降低受影响家庭的癌症相关死亡率至关重要。尽管推荐对结直肠癌和子宫内膜癌进行普遍筛查，并且提出了年龄限制筛查作为替代方案，但需要涵盖更广泛癌症类型的 LS 筛查。在本研究中，我们阐明了 dMMR 肿瘤的发生率，并评估了在年轻发病的结外 LS 相关癌症中进行 LS 筛查的结果。
回顾性地对 309 例年龄<50 岁的子宫内膜、非黏液性卵巢、胃、尿路上皮、胰腺、胆道和肾上腺癌患者的组织样本进行了 MMR 蛋白免疫组织化学检测。从病历中获得了临床病理信息和基因检测结果。
共有 24 例 dMMR 肿瘤（7.8%），包括 18 例子宫内膜癌、3 例卵巢癌、2 例尿路上皮癌和 1 例胃癌。dMMR 肿瘤患者中结直肠癌和 LS 相关癌症家族史的同时发生明显更为丰富。在接受免疫组织化学结果告知的 16 例 dMMR 肿瘤患者中，5 例子宫内膜癌和 1 例尿路上皮癌被诊断为 LS，存在 MMR 基因的阳性致病性变异。
我们报告了在多种年轻发病的结外 LS 相关癌症中进行 MMR 蛋白免疫组织化学检测的结果。我们的研究表明，对年轻发病的各种结外 LS 相关癌症患者进行全面的 LS 筛查方案是可行的。
