Yamamoto Nao, Tashiro Hironori, Katabuchi Hidetaka
Dept. of Obstetrics and Gynecology, Faculty of Life Science, Kumamoto University.
Gan To Kagaku Ryoho. 2018 Nov;45(11):1577-1581.
Among gynecological cancers, microsatellite instability(MSI)is most commonly found in endometrial carcinoma. When an allelic variation is observed in multiple microsatellite regions, it is called MSI-high(MSI-H). Hereditary MSI-H endometrial cancer develops through a germline mutation ofthe mismatch repair(MMR)gene, resulting in Lynch syndrome, and increased risk ofsporadic MSI-H endometrial cancer is caused by somatic lineage mutations or methylation abnormalities. Clinical characteristics ofendometrial cancer involved in Lynch syndrome include symptoms such as onset at a younger age, a lower corpus segment at the site, earlier stage cancer, and varied histology, when compared with those ofthe sporadic cancer. Alternatively, somatic mutations ofthe MMR gene are highly heterogeneous; however, a meta-analysis showed no difference in prognosis between with and without MSI-H. MSI-H is considered to be a biomarker, showing the therapeutic effects of an immune checkpoint inhibitor. A recent randomized controlled trial(RCT)demonstrated that an immune checkpoint inhibitor was effective against colorectal cancer with MSI-H. An additional RCT proved its effectiveness for MSI-H solid cancers, regardless oforgan type, including endometrial cancer. As the number ofcases ofendometrial cancer is increasing in Japan, MSI-H may hold utility as a biomarker for new molecular-target drugs, including immune checkpoint inhibitors. Ongoing surveillance ofcarcinomas in patients and family members is important because endometrial carcinoma associated with Lynch syndrome is a hereditary tumor. However, there is currently no established surveillance method for endometrial cancer. To improve the overall prognosis ofpatients with Lynch syndrome, genetic counseling and cross-division management are necessary, and also establishing the system is urgently required.
在妇科癌症中，微卫星不稳定性（MSI）最常见于子宫内膜癌。当在多个微卫星区域观察到等位基因变异时，称为微卫星高度不稳定（MSI-H）。遗传性MSI-H子宫内膜癌通过错配修复（MMR）基因的种系突变发展而来，导致林奇综合征，散发性MSI-H子宫内膜癌风险增加是由体细胞系突变或甲基化异常引起的。与散发性癌症相比，林奇综合征相关子宫内膜癌的临床特征包括发病年龄较轻、病变部位较低、癌症分期较早以及组织学类型多样等症状。另外，MMR基因的体细胞突变具有高度异质性；然而，一项荟萃分析显示MSI-H与非MSI-H患者的预后并无差异。MSI-H被认为是一种生物标志物，可显示免疫检查点抑制剂的治疗效果。最近一项随机对照试验（RCT）表明，免疫检查点抑制剂对MSI-H结直肠癌有效。另一项RCT证明了其对MSI-H实体癌有效，无论器官类型如何，包括子宫内膜癌。由于日本子宫内膜癌病例数不断增加，MSI-H可能作为包括免疫检查点抑制剂在内的新型分子靶向药物的生物标志物。对患者及其家庭成员的癌症进行持续监测很重要，因为与林奇综合征相关的子宫内膜癌是一种遗传性肿瘤。然而，目前尚无针对子宫内膜癌的确立的监测方法。为改善林奇综合征患者的总体预后，遗传咨询和跨科室管理是必要的，而且迫切需要建立相关体系。
