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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 investigate the relationship between the expression of zeste enhancer homolog 2 (EZH2) protein in Chinese Ewing sarcoma (EWS) patients and the clinicopathological parameters and prognosis. Methods Sixty-six Ewing’s sarcoma / primitive neuroectodermal tumors (EWS / PNET) and other small cell malignant tumors paraffin-embedded specimens were collected for tissue microarray. Ewing’s sarcoma rupture site 1 (EWSR1) was detected by fluorescence in situ hybridization Gene translocation; Immunohistochemistry was used to detect the expression of EZH2, Ki-67 and P53 in tumor tissue samples; Survival analysis was performed by Kaplan-Meier (KM) and Cox multivariate analysis. Results EHS protein was detected in 44 cases of paraffin-embedded tissues. The high expression of EZH2 protein in EWS tissues was closely related to lung metastasis and prognosis (P = 0.023, P = 0.004), and positively correlated with Ki-67 expression = 0.006). EZH2 overexpression and high Ki-67 proliferation index were significantly correlated with poor prognosis (P = 0.006, P = 0.023). Cox multivariate analysis showed that the overall survival of P53 was not significantly different from that of EWS (P > 0.05). However, EZH2 and Ki-67 were independent prognostic factors influencing the overall survival of patients (HR = 3.467,95% CI = 1.138-10.563, P = 0.029; HR = 2.140,95% CI = 0.439-10.423, P = 0.046). Further analysis showed that EZH2 and Ki-67 simultaneously expressed the lowest subpopulation survival (P = 0.012). Conclusions The expression of EZH2 and Ki-67 is an independent prognostic factor in EWS patients. Combined detection of EZH2 and Ki-67 can identify a subset of patients with very poor prognosis. EZH2 may be a new prognostic marker of EWS.