微卫星不稳定状态对Ⅳ期结直肠癌患者化疗反应性和预后的影响

摘要

背景与目的：错配修复缺陷导致的微卫星不稳(microsatellite inistability，MSI)状态对Ⅱ、Ⅲ期结直肠癌患者的预后及化疗敏感性有重要作用，但在晚期肠癌中研究较少。该研究探讨微卫星不稳对晚期结直肠癌患者化疗敏感性及预后的影响。方法：收集采用XELOX或FOLFOX为一线化疗方案的Ⅳ期肠癌患者的原发肿瘤组织，免疫组化方法检测肿瘤组织中错配修复基因hMLH1、hMSH2、hMSH6和hPMS2的蛋白表达，分析微卫星状态与患者临床特征、预后及化疗反应的相关性。结果：共收集113例晚期结直肠癌患者，未发现MSI与患者总体生存时间(overall survival，OS)以及化疗敏感性存在相关。亚组分析中我们发现79例原发灶姑息性切除的患者中，MSI 患者(22例)较MSS患者(57例)的中位无疾病进展时间(progression-free survival，PFS)明显延长(19.9个月vs 7个月，P=0.005)，但MSI与OS无关(P=0.07)。对该79例患者预后行Cox多因素分析显示，MSI是影响患者PFS的独立危险因素(P=0.043，MSS/MSI，HR=2.079)。此外，该群患者的MSI状态与疾病控制率(59.1%vs 31.6%，P=0.025)相关。结论：在原发灶姑息性切除的Ⅳ期结直肠癌患者中，微卫星不稳定状态与无疾病进展时间和化疗的疾病控制率呈正相关，因而有必要对该群患者进行微卫星检测。%Background and purpose:Microsatellite instability (MSI) status is commonly applied to predict the prognosis and chemosensitivity in stage Ⅱ and stage Ⅲ colorectal cancer patients. However, researches of its function on metastasis colorectal cancer are limited. This study investigated its value on prognosis and chemosensitivity in metastatic colorectal cancer (CRC) patients.Methods:We retrospectively investigated tumor tissues from metastasis CRC patients who were treated with oxaliplatin and 5-FU-based therapy regimens (FOLFOX and XELOX). Immunostaining of proteins of the mismatch repair genehMLH1,hMSH2,hMSH6 andhPMS2 was performed. Prognostic value and chemosensitivity in patients with MSI status were also determined.Results:Clinical features from 113 patients were analyzed. No cor-relation of overall survival (OS) and chemosensitivity with MSI status was found. We further investigated 79 patients with synchronous metastasis and palliatively tumor resection. Median progression free survival (PFS) from 22 MSI patients was significant longer than that in 57 MSS patients (19.9 monthsvs 7 months,P=0.005). No significant difference was seen in OS comparison (P=0.07). MSI status was also an independent prognostic factors of PFS by Cox multivariate analysis (MSS/MSI,HR=2.079,P=0.043). Moreover, in this group, MSI patients had improved disease control rate (59.1%vs 31.6%, P=0.025) in chemosensitivity analysis than MSS patients.Conclusion:A better PFS in MSI patients with synchronous metastasis and palliative tumor resection was found after treated with oxaliplatin and 5-FU-based therapy and a better chemosensitivity in MSI patients was also found.