摘要目的：探讨儿童神经母细胞源性肿瘤（NT）中TOP2A蛋白的表达及其基因拷贝数的变化，并分析其临床病理意义。方法收集89例甲醛液固定、石蜡包埋NT组织标本，其中包括神经母细胞瘤（NB）68例、节细胞神经母细胞瘤（GNB）18例、节细胞神经瘤（GN）3例。运用免疫组织化学技术检测TOP2A蛋白的表达；运用间期荧光原位杂交（ FISH）技术检测TOP2A基因拷贝数的变化。结果组织足够的88例NT中，52例（59.1％，52／88） TOP2A蛋白表达阳性，其中21例（23.9％，21／88）高表达。随着NT分化程度的升高，TOP2A的表达量减少（P＝0.006）。随着Ki-67指数（P＜0.01）及有丝分裂／核碎裂指数（ MKI，P＝0.001）的升高，TOP2A的表达量增加。获得满意荧光信号的80例NT中，28例（35.0％，28／80）存在TOP2A基因的扩增。随着NT分化程度的升高，TOP2A的扩增率增加（ P＝0.014）。 TOP2 A在年龄较大（＞18个月， P＜0.01）、临床分期较高（Ⅲ、Ⅳ期；P＝0.028）、高危组（P＝0.001）病例中更易发生扩增。随着Ki-67指数的降低，TOP2A的扩增率增加（ P＝0.040）。经单因素生存差异分析显示，随着TOP2A表达量的增加，NT患儿的生存率下降（ P＝0.005）。经Cox比例风险回归模型进行预后因素的多变量分析显示，TOP2A表达是影响NT患儿预后的不利因素（ P＝0.010）。结论超过半数的NT表达TOP2A。 TOP2A的表达随NT分化程度的升高而减少，随着Ki-67指数、MKI的升高而增加；TOP2A表达是NT的独立预后不良因子，随着TOP2A表达的升高，患儿的生存率下降。约三分之一的NT出现TOP2A的扩增，在年龄较大、高危的晚期病例中TOP2A扩增率较高。TOP2A的检测有可能为适合蒽环类药物治疗的NT患儿的筛选提供参考。

abstractsObjective To detect TOP2A protein expression and gene copy number alterations, and to analyze related clinical and pathological implications in pediatric neuroblastic tumors ( NT ).Methods Immunohistochemistry was used to detect TOP2A protein expression.Fluorescence in situ hybridization (FISH) was used to detect numerical aberrations of TOP2A.Results TOP2A protein was expressed in 59.1%(52/88) of cases, which was associated with differentiation (P=0.006), Ki-67 index (P<0.01) and MKI (P=0.001).Twenty-eight cases (35.0%, 28/88) showed TOP2A gene amplification, which was correlated with the age (P<0.01), clinical stage (P=0.028), high risk group (P=0.001), Ki-67 index (P=0.040) and differentiation (P=0.014).Survival analysis showed that TOP2A expression was related to survival rate.Multivariate analyses showed that TOP2A expression was an independent predictor for poor prognosis (P=0.010).Conclusions More than half of the cases show TOP2A expression, which is more likely associated with NB, high Ki-67 index and high MKI.Cases with TOP2A expression have shorter survivals and poorer prognosis.TOP2A amplification is seen in 35% and likely occurs in patients older than 18 months and at advanced INSS stages (Ⅲ and Ⅳ).As a target of the anthracycline-based adjuvant drugs, TOP2A test can be used to select patient with NT for the therapy.