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.
错配修复蛋白的胚系突变（林奇综合征，LS）与体细胞缺陷与结直肠癌和子宫内膜癌相关，但其在亚洲人群中的预后影响尚不明确。本前瞻性队列研究旨在确定疑似LS癌症患者中胚系与体细胞错配修复缺陷的发生率及临床结局。研究纳入疑似LS的结直肠癌或子宫内膜癌患者，对其进行胚系错配修复缺陷基因测序，并对部分病理样本进行错配修复蛋白免疫组化染色以检测体细胞缺陷。在451例入组患者中，36例存在胚系错配修复缺陷。与胚系缺陷阴性患者相比，胚系缺陷阳性患者的10年无复发生存率显著更高（100% vs. 77.9%；p=0.006），而10年总生存率相近（100% vs. 90.9%；p=0.12）。在102例可获得体细胞错配修复状态的胚系缺陷阴性患者中，13.7%存在体细胞错配修复缺陷。胚系缺陷阴性/体细胞缺陷阳性患者的5年无复发生存率为62.9%，胚系缺陷阴性/体细胞缺陷阴性患者为35.0%，两者均低于胚系缺陷阳性患者（100%；p<0.001）。本研究表明林奇综合征可为结直肠癌和子宫内膜癌患者带来更优预后，并强调在检测到体细胞错配修复缺陷后进行胚系基因检测的重要性。
肿瘤(癌症)患者之家