错配修复/微卫星不稳定性对晚期结直肠癌化疗敏感性及预后的影响

Significance of mismatch repair/microsatellite instability in the chemotherapy sensitivity and prognosis of late-stage colorectal cancer

目的探究错配修复/微卫星不稳定性(MSI)在晚期结直肠癌化疗敏感性及临床转归中的意义。方法收集2009年12月～2016年12月在扬州大学附属医院肿瘤科的接受FOLFOX或XELOX一线方案化疗的181例晚期结直肠癌患者的原发肿瘤组织,采用免疫组化方法检测肿瘤组织MLH1、PMS2、MSH2、MSH6 4种蛋白的表达情况,并分为MSI组(18例)和微卫星稳定组(MSS组,163例),比较两组在化疗敏感性和预后中的差异。结果除了病变部位外(P <0.05),其他临床特征在MSI组及MSS组中差异均无统计学意义(P> 0.05)。采用Kaplan-Meier生存曲线对随访资料进行分析,MSI组和MSS组的患者总体生存时间差异无统计学意义(P> 0.05)。化疗敏感性方面,MSI组和MSS组的化疗总有效率差异无统计学意义(P> 0.05),但是MSI组疾病控制率显著高于MSS组,差异有统计学意义(P <0.05)。结论 MSI状态与晚期结直肠癌患者的总生存时间无关,与疾病控制率有关。因此,MSI可以作为评估晚期结直肠癌患者化疗效果的重要指标。

Objective To investigate the significance of mismatch repair/microsatellite instability (MSI) in the chemotherapy sensitivity and prognosis of late-stage colorectal cancer (CRC). Methods From December 2009 to December 2016, in Affiliated Hospital of Yangzhou University, 181 primary tumor tissues were collected from CRC patients who received first-line chemotherapy (FOLFOX or XELOX). Immunohistochemistry was used to detect the expression of MLH1, PMS2, MSH2 and MSH6 in tumor tissues. Based on the staining results, they were divided into MSI group (18 cases) and microsatellite stability (MSS) group (163 cases). The intergroup difference in chemotherapy sensitivity and prognosis were analyzed. Results Except for tumor location (P < 0.05), the differences were not statistically significant in clinical features between two groups (P > 0.05). Kaplan-Meier model was used to analyze follow-up data, there was no statistically significant difference in patient prognosis of two groups (P > 0.05). In chemotherapy sensitivity, there was no statistically significant difference in the total effective rate of two groups (P > 0.05). However, disease control rate of MSI group was significant higher than MSS group, the difference was statistically significant (P < 0.05). Conclusion Although MSI status is not related with the prognosis of late-stage CRC patients, but it is correlated with disease control rate. Therefore, MSI can act as an important marker for evaluating the chemotherapy efficacy in late-stage CRC patients.