EZH2表达与结直肠癌肿瘤细胞增殖和血管生成及预后的关系

摘要

[Objective]To evaluate the expression of enhancer of zeste homolog 2(EZH2),Ki-67 and intratumoral microvaseu?lar density(iMVD)in human colorectal cancer(CRC),and discuss their relationship with the biological behavior and prognosis.[Methods]The expression of EZH2,Ki-67 and iMVD(labeled by CD34 protein)was measured with immunohistochemical MaxVision method in CRC patients followed up over 5 years.[Results]Positive expression rates of EZH2,Ki-67 and iMVD were 40.91%(45/110),57.27%(63/110)and 46.36%(51/110),respectively. EZH2 expression was positively correlated with distant metastasis(P=0.024). Ki-67 expression was positively correlated with tumor size,infiltration depth,AJCC stage and differentiation(P=0.033~0.015). The iMVD expression was positively correlated with infiltration depth ,AJCC stage and differentiation (P=0.016~0.034). Spearman correlation analysis showed that EZH2 expression was positively correlated with Ki-67 expression(r=0.195,P=0.041), whereas negatively correlated with iMVD expression. Ki-67 expression had a positive correlation with iMVD(r=0.213,P=0.025). Multivariate analysis suggested that the EZH2 expression was an adverse independent factor for survivals of CRC patients(HR 1.965, 95%CI:1.019-3.789,P=0.044 for OS).[Conclusion]EZH2 expression was significantly correlate with the proliferation of tumor cells and may plays an important role in the metastasis and prognosis of CRC.%[目的]探讨果蝇zeste基因增强子同源物2(EZH2)表达与结直肠癌肿瘤细胞增殖、血管生成及预后的关系.[方法]采用免疫组织化学MaxVision两步法检测110例手术切除的原发性结直肠腺癌组织中EZH2、增殖细胞核抗原(Ki-67)和CD34标记血管内皮细胞计数肿瘤微血管密度(iMVD)的表达情况,并分析其与结直肠癌临床病理特征的关系.用Pearson相关系数分析EZH2、Ki-67及iMVD表达的相关性.用Kaplan-Meier法分析生存曲线,多变量Cox比例风险回归模型筛选影响患者生存的独立预后因素.[结果]结直肠癌组织的EZH2、Ki-67及iMVD阳性表达率分别为40.91%(45/110)、57.27%(63/110)和46.36%(51/110).结直肠癌远处转移患者的EZH2蛋白阳性表达率高于无远处转移患者(P=0.024).Ki-67与原发灶大小、肠壁浸润深度、AJCC分期、分化程度密切相关(P=0.033~0.015).iMVD与肿瘤的肠壁浸润深度、AJCC分期、分化程度密切相关(P=0.016~0.034).Spearman相关分析显示EZH2与Ki-67呈正相关(r=0.195,P=0.041),而与iMVD的表达无关;Ki-67与iMVD呈正相关(r=0.213,P=0.025).多因素分析结果表明,EZH2蛋白的表达是结直肠癌患者预后差的独立影响因素(HR 1.965,95%CI 1.019~3.789,P=0.044).[结论]结直肠癌组织中EZH2过表达与肿瘤细胞的增殖活性有关,在一定程度上EZH2具有判断结直肠癌切除术后转移和预后的价值.