微卫星不稳定结直肠癌临床病理特征及生存预后

Colinicopathologic features and prognosis of colorectal cancer patients with microsatellite instability

目的国内外已有学者提出微卫星不稳定(microsatellite instability,MSI)状态可能是影响结直肠癌(colorectal cancer,CRC)患者预后的因素,同时提出微卫星不稳定结直肠癌患者存在较为特殊的临床病理特征,本研究旨在探讨微卫星不稳定CRC的临床病理特征及生存预后。方法应用免疫组织化学方法检测2010-03-24-2015-12-24济南市第四人民医院60例CRC组织中人MutL蛋白同系物1(human mutl homologue 1,hMLH1)、人MutS蛋白同系物2(human muts homologue 2,hMSH2)及人MutS蛋白同系物6(human muts homologue 6,hMSH6)3种DNA错配修复蛋白表达缺失情况,判断肿瘤微卫星不稳定状态,并分析高度微卫星不稳定(microsatellite instability-high,MSI-H)和低度微卫星不稳定(microsatellite instability-low,MSI-L)/微卫星稳定(microsatellite stable,MSS)不同组别间的临床病理特征及生存预后情况;应用Cox风险比例模型对可能影响CRC患者预后的因素进行多因素分析。结果 60例CRC患者的肿瘤组织中MSI-H为40.0%(24/60),MSI-L为31.7%(19/60),MSS为28.3%(17/60)。MSI-H的CRC患者,与MSS和MSI-L患者相比,好发于右半结肠(χ~2=6.279,P=0.043),黏液腺癌多见(χ~2=6.025,P=0.049);3组在性别、年龄、分期、肿瘤浸润深度、淋巴结转移和分化程度差异无统计学意义。MSI-H患者的中位无病生存期(disease-free survival,DFS)为21个月,明显长于MSS的11个月及MSI-L的13个月,χ~2=7.994,P=0.018。多因素Cox分析结果显示,淋巴结转移(P=0.013)和MSI(P=0.018)为CRC患者DFS的独立预后因素。结论 MSI-H的CRC患者与MSI-L及MSS相比,具有独特的临床病理特征且预后相对较好。检测MSI状态对提高CRC治疗水平,及改善预后有重要的临床意义。

OBJECTIVE Some scholars suggest that microsatellite instability（MSI）may become an influence factors for the prognosis of patients with colorectal cancer and they also suggest that patients with microsatellite instability have special clinicalpathologic features.The purpose of this study was to explore the colinicopathologic features and prognosis of colorectal cancer patients with microsatellite instability.METHODS Immunohistochemistry was used to detect the human mutl homologue 1（hMLH1）,human muts homologue 2（hMSH2）or Human muts homologue 6（hMSH6）protein expression in the tumor tissues from 60 cases of Fourth People＇s Hospital of Jinan（2010-03-24-2015-12-24）to predict tumor MSI status and analyze colinicopathologic features and prognosis of colorectal cancer patients with Microsatellite instability-high（MSI-H）and Microsatellite instability-low（MSI-L）/Microsatellite stable（MSS）.Clinicopathologic factors related to prognosis of patients with colorectal cancer were analyzed by multivariate COX proportional hazards model.RESULTS The MSI-H,MSI-L and MSS in the tumor tissues from 60 patients were 40.0%（24/60）,31.7%（19/60）,28.3%（17/60）,respectively.MSI-H was good in the right colon（χ~2=6.279,P=0.043）,mucinous adenocarcinoma（χ~2=6.025,P=0.049）.There was no significant difference in gender,age,clinical stage,depth of tumor invasion,lymph node metastasis and differentiation degree among the three groups：The median Disease-free survival（DFS）of MSI-H significantly longer than MSS and MSI-L patients（χ~2=7.994,P=0.018）,there median Disease-free survival were 21 months,11months,13 months,respectively.Multivariate analysis revealed that lymph node metastasis（P=0.013）and MSI（P=0.018）were independent prognostic factors of DFS in patients with colorectal cancer.CONCLUSIONS Compared with MSI-L and MSS,MSI-H colorectal cancer patients have unique clinical and pathological features and have relatively good prognosis.Detection of MSI status is very important for improving the level of colorectal cancer treatment and the prognosis.