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。
Objective 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.
出处
《中华病理学杂志》
CAS
CSCD
北大核心
2016年第11期748-754,共7页
Chinese Journal of Pathology