Background: The mismatch repair (MMR) system prevents DNA mutation; therefore, deficient MMR protein (dMMR) expression causes genetic alterations and microsatellite instability (MSI). dMMR is correlated with a good outcome and treatment response in various cancers; however, the situation remains ambiguous in cholangiocarcinoma (CCA). This study aims to evaluate the prevalence of dMMR and investigate the correlation with clinicopathological features and the survival of CCA patients after resection. Materials and Methods: Serum and tissues were collected from CCA patients who underwent resection from January 2005 to December 2017. Serum OV IgG was examined using ELISA. The expression of MMR proteins MLH1, MSH2, MSH6 and PMS2 was investigated by immunohistochemistry; subsequently, MMR assessment was evaluated as either proficient or as deficient by pathologists. The clinicopathological features and MMR status were compared using the Chi-square test. Univariate and multivariate analyses were conducted to identify prognostic factors. Results: Among the 102 CCA patients, dMMR was detected in 22.5%. Survival analysis revealed that dMMR patients had better survival than pMMR (HR = 0.50,p= 0.008). In multivariate analysis, dMMR was an independent factor for a good prognosis in CCA patients (HR = 0.58,p= 0.041), especially at an early stage (HR = 0.18,p= 0.027). Moreover, subgroup analysis showed dMMR patients who received adjuvant chemotherapy had better survival than surgery alone (HR = 0.28,p= 0.012). Conclusion: This study showed a high prevalence of dMMR in cholangiocarcinoma with dMMR being the independent prognostic factor for good survival, especially in early-stage CCA and for patients who received adjuvant chemotherapy. dMMR should be the marker for selecting patients to receive a specific adjuvant treatment after resection for CCA.
背景：错配修复（MMR）系统可防止DNA突变，因此MMR蛋白表达缺失（dMMR）会导致基因改变和微卫星不稳定性（MSI）。dMMR与多种癌症的良好预后和治疗反应相关，但在胆管癌（CCA）中的情况仍不明确。本研究旨在评估dMMR的患病率，并探讨其与胆管癌患者切除术后临床病理特征及生存期的相关性。 材料与方法：收集2005年1月至2017年12月期间接受切除术的胆管癌患者的血清和组织样本。采用ELISA法检测血清OV IgG水平。通过免疫组织化学检测MMR蛋白MLH1、MSH2、MSH6和PMS2的表达；随后由病理学家评估MMR状态为功能完整或功能缺失。采用卡方检验比较临床病理特征与MMR状态。通过单因素和多因素分析确定预后因素。 结果：在102例胆管癌患者中，dMMR检出率为22.5%。生存分析显示dMMR患者比pMMR患者生存期更长（HR=0.50，p=0.008）。多因素分析表明，dMMR是胆管癌患者良好预后的独立因素（HR=0.58，p=0.041），尤其在早期阶段更为显著（HR=0.18，p=0.027）。此外，亚组分析显示接受辅助化疗的dMMR患者比单纯手术患者生存期更长（HR=0.28，p=0.012）。 结论：本研究表明胆管癌中dMMR具有较高患病率，且dMMR是良好生存期的独立预后因素，尤其对早期胆管癌患者及接受辅助化疗的患者具有显著意义。dMMR应作为胆管癌切除术后选择特定辅助治疗患者的标志物。
肿瘤(癌症)患者之家