间变性大细胞淋巴瘤激酶蛋白在儿童外周神经母细胞性肿瘤中的表达及意义

Expression and Significance of Anaplastic Large Cell Lymphoma Kinase Protein in Peripheral Neuroblastic Tumors

目的探讨间变性大细胞淋巴瘤激酶蛋白(ALK)在外周神经母细胞性肿瘤(pNT)中的表达及意义。方法收集46例pNT的临床病理资料,采用免疫组化方法检测ALK蛋白,荧光原位杂交技术检测N-MYC基因。结果46例患儿临床分期:Ⅰ~Ⅱ期和Ⅲ~Ⅳ期各23例;病理诊断:神经母细胞瘤(NB)40例、节细胞性神经母细胞瘤(GNB)6例,其中预后良好型(FH型)32例、预后不良型(UH型)14例;ALK在NB和GNB中的阳性表达率分别为55%(22/40)和0(0/6),差异具有统计学意义(P=0.038)。40例NB中N-MYC基因扩增阳性4例、获得7例,6例GNB均无N-MYC基因扩增和获得。15例新生儿NB中ALK蛋白阳性表达率为40%(6/15),100%N-MYC基因扩增阴性。ALK蛋白在Ⅲ~Ⅳ期、UH型和N-MYC基因异常中表达率高,差异具有统计学意义(P=0.018、0.001、0.010),在不同性别、年龄和部位间无差异表达(P=0.382、0.400、0.617)。结论儿童pNT应常规检测ALK蛋白,其阳性表达与病理分型和临床分期有一定的关系。不同年龄段NB中ALK蛋白的表达意义及机制有待进一步研究。

Objective To investigate the expression and significance of anaplastic large cell lymphoma kinase protein(ALK)in peripheral neuroblastoma(pNT).Methods The clinicopathological data of 46 cases of pNT were collected.ALK protein was detected by immunohistochemistry and N-MYC gene was detected by fluorescence in situ hybridization(fish).Results Among the 46 cases,stageⅠ~Ⅱ(n=23)and stageⅢ~Ⅳ(n=23).Pathological diagnosis:there were 40 cases of neuroblastoma((NB))and 6 cases of ganglioneuroblastoma((GNB)),including 32 cases of good prognosis(FH type)and 14 cases of poor prognosis(UH type).The positive expression rates of ALK in NB and GNB were 55%(22pm 40)and 0(0pm 6),respectively,and the difference was statistically significant.In 40 cases of NB,4 cases were positive for N-MYC gene amplification,7 cases were obtained,and 6 cases of GNB did not have N-MYC gene amplification and acquisition.In 15 cases of neonatal NB,the positive expression rate of ALK protein was 40%(6 times 15),and the amplification of N-MYC gene was negative(15 times 15).The expression of ALK protein was high inⅢ~Ⅳstage,UH type and N-MYC gene abnormality,and the difference was statistically significant(Purge 0.018,0.001,0.010),but there was no significant difference in different sex,age and location(P>0.05).There was no difference in the expression of UH type and N-MYC gene(0.382,0.400,0.617).Conclusion ALK protein should be detected routinely in children with pNT,and its positive expression is related to pathological classification and clinical stage.The significance and mechanism of ALK protein expression in different age groups of NB need to be further studied.