Yan Wen-Yue, Hu Jing, Xie Li, Cheng Lei, Yang Mi, Li Li, Shi Jiong, Liu Bao-Rui, Qian Xiao-Ping
The Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine.
The Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine; The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University.
Onco Targets Ther. 2016 Dec 8;9:7415-7424. doi: 10.2147/OTT.S117089. eCollection 2016.
Colorectal cancers (CRCs) exhibiting microsatellite instability (MSI) have special biological behavior. The clinical predictors for MSI and its survival relevance for the Chinese population were still unclear. Seven hundred ninety-five CRC patients were retrospectively assessed. Mismatch repair (MMR) proteins (MSH2, MSH6, PMS1, and MLH1) expression was detected by immunohistochemistry using tumor tissues of all patients. DNA MSI status was analyzed by polymerase chain reaction in 182 samples randomly selected from the 795 cases. Among all CRC tumor tissues, 97 cases (12.2%) were with an MMR protein-deficient (MMR-D) phenotype, whereas 698 cases (87.8%) were with an MMR proteins intact (MMR-I) phenotype. A total of 21 (11.5%) CRCs were identified as having high microsatellite instability, 156 (85.7%) tumors were having microsatellite stability (MSS), and five (2.7%) were having low microsatellite instability. Importantly, MMR status was demonstrated to be moderately consistent with MSI status (κ=0.845, 95% confidence interval [CI] 0.721, 0.969). Unconditional logistic regression analysis revealed age, number of lymph node, tumor diameter, and tumor site as predictors for MSI with a substantial ability to discriminate different MSI status by area under curve of 80.62% using receiver operation curve. Compared with MMR-I, MMR-D was an independent prognostic factor for longer overall survival (hazard ratio =0.340, 95% CI 0.126, 0.919; =0.034). MMR-D is an independent prognostic factor for better outcome. Our results may provide evidence for individualized diagnosis and treatment of CRC, but this will require further validation in larger sample studies.
表现出微卫星不稳定性（MSI）的结直肠癌（CRC）具有特殊的生物学行为。MSI的临床预测因素及其与中国人群生存的相关性仍不明确。对795例CRC患者进行了回顾性评估。使用所有患者的肿瘤组织通过免疫组织化学检测错配修复（MMR）蛋白（MSH2、MSH6、PMS1和MLH1）的表达。从795例病例中随机选取182个样本，通过聚合酶链反应分析DNA MSI状态。在所有CRC肿瘤组织中，97例（12.2%）具有MMR蛋白缺陷（MMR-D）表型，而698例（87.8%）具有MMR蛋白完整（MMR-I）表型。共鉴定出21例（11.5%）CRC具有高微卫星不稳定性，156例（85.7%）肿瘤具有微卫星稳定性（MSS），5例（2.7%）具有低微卫星不稳定性。重要的是，MMR状态与MSI状态呈中度一致性（κ=0.845，95%置信区间[CI]0.721，0.969）。无条件逻辑回归分析显示，年龄、淋巴结数量、肿瘤直径和肿瘤部位是MSI的预测因素，使用受试者工作特征曲线，其通过曲线下面积区分不同MSI状态的能力较强，为80.62%。与MMR-I相比，MMR-D是总生存期更长的独立预后因素（风险比=0.340，95%CI 0.126，0.919；P=0.034）。MMR-D是预后较好的独立预后因素。我们的结果可能为CRC的个体化诊断和治疗提供证据，但这需要在更大样本研究中进一步验证。
