中国尤文肉瘤患者EZH2蛋白表达与临床病理学参数及预后的关系

Expression of EZH2 in Chinese Ewing sarcoma patients and its relationship with clinicopathological parameters and prognosis

目的探讨果蝇zeste增强子同源物2(EZH2)蛋白在中国尤文肉瘤(EWS)患者中的表达与临床病理参数特征及预后的关系。方法收集67例尤文肉瘤/原始神经外胚层肿瘤(EWS/PNET)和其他小圆细胞恶性肿瘤石蜡标本并构建组织芯片,采用荧光原位杂交(FISH)法检测尤文肉瘤断裂位点1(EWSR1)基因易位;应用免疫组织化学法检测肿瘤组织标本中EZH2、Ki-67和P53的表达;应用Kaplan-Meier(K-M)和Cox多因素分析法进行生存分析。结果确诊EWS石蜡组织标本44例;EZH2蛋白在EWS组织中的高表达与肺转移及预后密切相关(P=0.023,P=0.004),并且与Ki-67表达呈正相关性(R=0.406,P=0.006)。EZH2高表达和高Ki-67增殖指数与患者不良预后呈显著相关性(P=0.006,P=0.023);Cox多因素分析表明,P53的表达与EWS患者的总体生存差异无统计学意义(P>0.05),但EZH2和Ki-67是影响患者总体生存的独立预后判定因子(HR=3.467,95%CI=1.138~10.563,P=0.029;HR=2.140,95%CI=0.439~10.423,P=0.046)。进一步分析显示,EZH2和Ki-67同时高表达的亚群生存期最短(P=0.012)。结论 EZH2和Ki-67的表达是EWS患者的独立预后因素,并且EZH2和Ki-67的联合检测可以识别预后极差的一部分EWS患者,EZH2可能是EWS新的预后标志物。

Objective To explore the expression of enhancer of zeste homolog 2（ EZH2） in Chinese Ewing sarcoma（ EWS） patients,and to analyze its correlation with the clinicopathological parameters and prognosis. Methods Tissues from 67 cases of Ewing sarcoma / primitive neuroectodermal tumor（ EWS / PNET） and other small round cell malignant tumors were collected and microarrayed. Gene rearrangement in EWS region 1（ EWSR1） was evaluated using fluorescence in situ hybridization（ FISH）. The expressions of EZH2,P53 and Ki-67 were determined using immunohistochemical method. Survival analysis was performed with Kaplan-Meier and Cox method. Results A total of 44 cases were confirmed EWS. EZH2 expression was closely related to lung metastasis（ P = 0. 023） and prognosis（ P =0. 004） in EWS tissues,and positively correlated to the expression of Ki-67（ R = 0. 406,P = 0. 006）. There was significant correlation between poor prognosis and high expression of EZH2（ P = 0. 06） and high proliferation index of Ki-67（ P = 0. 023）. Cox multivariate analysis revealed that there was no significant correlation between P53 expression and overall survival（ P〈0. 05）; EZH2 and Ki-67 were independent risk factors for overall survival（ HR = 3. 467,95%CI = 1. 138-10. 563,P = 0. 029; HR = 2. 140,95% CI = 0. 439-10. 423,P = 0. 046）. In addition,a subset of EWS patients with overexpression of both EZH2 and Ki-67 had the shortest survival time（ P = 0. 012）. Conclusion EZH2 andKi-67 are independent prognostic factors in Chinese EWS patients. A combined detection of EZH2 and Ki-67 can help to identify the subset with extremely poor prognosis. EZH2 may serve as a novel prognostic marker of Ewing sarcoma.