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Abstract：
Germline (Lynch syndrome, LS) and somatic deficiencies of mismatch repair proteins (MMRd) are linked to colorectal and endometrial cancer; however, their prognostic impact in Asian populations remains unclear. This prospective cohort study aimed to determine the prevalence and outcome of germline and somatic MMRd in cancer patients suspected of LS. Patients with colorectal or endometrial cancer suspected of LS were enrolled and underwent gene sequencing for germline MMRd (gMMRd) and immunohistochemistry staining of MMR proteins in a subset of the pathological samples (pMMRd). Among the 451 enrolled patients, 36 patients were gMMRd (+). Compared with gMMRd (-) patients, the 10-year relapse-free survival in gMMRd (+) patients was significantly higher (100% vs. 77.9%; p = 0.006), whereas the 10-year overall survival was similar (100% vs. 90.9%; p = 0.12). Among the 102 gMMRd (-) patients with available pMMR status, 13.7% were pMMRd (+). The 5-year relapse-free survival was 62.9% in gMMRd (-) pMMRd (+) patients and 35.0% in gMMRd (-) pMMRd (-) patients, both lower than gMMRd (+) patients (100%; p < 0.001). This study showed that having LS confers a favorable outcome in colorectal and endometrial cancer patients and highlights the importance of germline genetic testing following the detection of somatic MMRd.
摘要：
种系（林奇综合征，LS）和体细胞缺陷的错配修复蛋白（MMRd）与结直肠癌和子宫内膜癌有关；然而，它们对亚洲人群的预后影响尚不清楚.这项前瞻性队列研究旨在确定怀疑LS的癌症患者中种系和体细胞MMRd的患病率和结果。纳入疑似LS的结直肠癌或子宫内膜癌患者，并对病理样本的一部分（pMMRd）进行种系MMRd（gMMRd）的基因测序和MMR蛋白的免疫组织化学染色。在451名患者中，36例患者均为gMMRd(+)。与gMMRd(-)患者相比，gMMRd(+)患者的10年无复发生存率明显较高(100%vs.77.9%；p=0.006），而10年总生存率相似(100%vs.90.9%；p=0.12）。在102名具有pMMR状态的gMMRd(-)患者中，13.7%为pMMRd(+)。gMMRd（-）pMMRd（-）患者的5年无复发生存率为62.9％，gMMRd（-）pMMRd（-）患者的5年无复发生存率为35.0％，均低于gMMRd(+)患者(100%;p<0.001)。这项研究表明，LS在结直肠癌和子宫内膜癌患者中具有良好的预后，并强调了在检测体细胞MMRd后进行种系遗传检测的重要性。
