儿童骨肉瘤中Survivin及其相关基因的表达与预后关系

Expressions of Survivin and related genes and their relationships with the prognosis in pediatric osteosarcoma

目的 探讨Survivin及VEGF、Bcl-2、Ki67基因在骨肉瘤中的表达情况与生物学特性关系及预后意义。方法应用免疫组化SP法检测34例原发性骨肉瘤组织中Survivin、VEGF、Bcl-2与Ki67的表达情况，分析检测结果与骨肉瘤临床病理和生物学行为及预后的关系。结果骨肉瘤组织中Survivin蛋白表达阳性率为67．60（23／34），表达与外科Enneking分期、远处肺转移、5年生存率相关，并降低化疗有效率；Survivin与VEGF、Bcl-2、Ki67表达呈正相关；生存分析显示Survivin高表达与患儿预后不良有关；采用COX比例风险模型进行多因素分析，骨肉瘤术前的Enneking外科分期，Survivin表达水平是骨肉瘤预后相关的独立的重要因素。结论Survivin可作为骨肉瘤诊断的标记及判断骨肉瘤预后的独立指标，与VEGF、Bcl-2、Ki67参与了骨肉瘤的恶性进展，且能降低对化疗的敏感性。

Objective To investigate the expressions of Survivin,VEGF,Bcl-2 and Ki67 in children with osteosarcoma. Methods The expressions of Survivin, VEGF, Bcl-2 and Ki67 were examined by SP imrnunohistochemieal technique in 34 osteosarcoma tissues. The profile was correlated with clinicopathologic parameters and prognosis. The possible factors which influenced prognosis in osteosarcoma were analyzed by COX multivariate analysis. Results The positive rate of Survivin was 67. 6 % （ 23/34） in all the 34 cases of osteosareoma. The positive Survivin expression were correlated with Enneking grade, distant lung metastasis and the five-year survival rate. There were statistically significant positive correlation between Survivin and VEGF,Bcl-2, or Ki67 expression. Survival analysis indicated that high expression of Survivin correlated with poor prognosis of patients with osteosarcoma. COX multivariate regression identified the Survivin expression levels and Enneking grade as independent predictors of survival in osteosarcoma. Conclusions Survivin is a molecular diagnostic marker as independent predictors of prognosis in osteosarcoma, and participates in the malignant progression of osteosarcoma with VEGF,Bcl-2 and Ki67 proteins. The expression of Survivin may reduce the chemosensitivity.