摘要目的 间变性大细胞淋巴瘤激酶蛋白(ALK)基因异常与神经母细胞瘤(neuroblastoma,NB)发病机制有关.本研究探讨ALK蛋白在神经母细胞瘤中的表达及其与临床特点和生存预后的关系.方法 收集2001年5月至2011年10月中山大学肿瘤防治中心初治的、经病理证实的神经母细胞瘤患儿的临床资料和蜡块组织标本,采用免疫组化方法检测组织中ALK蛋白表达情况,并分析其对神经母细胞瘤临床特点、生存预后的影响.结果 76例NB患儿纳入研究,中位年龄4岁(0.1～18岁),男52例,中位随访时间20.1个月.ALK蛋白在神经母细胞瘤中的阳性表达率为36.8％(28/76),其中高表达率26.3％(20/76),ALK蛋白高表达与低表达患儿的5年总生存(OS)分别为(28.3±14.9)％和(51.2±11.0)％,P=0.397.ALK的表达与年龄有关,年龄＞1.5岁的患儿中ALK蛋白高表达率为32.7％,而年龄≤1.5岁患儿仅为6.7％,P=0.043.Ⅲ期NB患儿中ALK的高表达与低表达的3年OS分别为0和(79.5±13.1)％,P=0.023;ALK蛋白表达与Ⅰ、Ⅱ、Ⅳ期患儿的生存无相关性.结论 ALK蛋白在中国NB患儿中有较高表达率,尤其年龄＞1.5岁的患儿.ALK高表达是Ⅲ期NB患儿的预后不良因素.ALK蛋白与ALK基因之间的关系以及在神经母细胞瘤中的发病机制需进一步研究.

abstractsObjective To explore the expression and clinical significance of ALK in neuroblastoma (NB) in China.Methods Tumor samples of 76 untreated NB patients were collected from May 2001 to October 2011 to examine the expression and clinical significance of ALK in NB by immunohistochemistry.Results There were 52 males and 24 females with a median age of 4 years.During a median follow-up period of 20.1 months,the positive expression rate for ALK was 36.8％ (28/76) in NB patients and the high expression rate 26.3％ (20/76).The 5-year overall survival (OS) of patients with ALK high and low expression were (28.3 ± 14.9)％ and (51.2 ± 11.0)％ respectively (P =0.397).The expression of ALK was correlated with patient age.The higher expression rate was 32.7％ in patients aged over 1.5 years versus 6.7％ in those aged under 1.5 years (P=0.043).The 3-year OS for those of stage Ⅲ with ALK high and low expression were 0 and (79.5 ± 13.1)％ respectively (P =0.023).But the expression level of ALK did not significantly affect the survival of stages Ⅰ,Ⅱ,Ⅳ and ⅣS patients.Conclusions The positive expression rate of ALK is high in neuroblastoma in China,especially in patients aged over 1.5 years.ALK high expression may be a poor prognostic factor for stage Ⅲ NB.The pathogenetic correlation between ALK protein and ALK gene aberrations in NB require further researches.