Liao R, Sun X F, Zhen Z Z, Huang D S
Department of Pediatric Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Zhonghua Er Ke Za Zhi. 2018 Oct 2;56(10):735-740. doi: 10.3760/cma.j.issn.0578-1310.2018.10.004.
To investigate the relationship between expression of programmed cell death ligand-1(PD-L1) in the tissue of neuroblastoma (NB) and patient's clinical characteristics and prognosis. Clinical data and surgical tissue paraffin blocks of 100 newly diagnosed NB children at Sun Yat-sen University Cancer Center between January 2000 and December 2015 were collected and the expression level of PD-L1 and its' relationship with pathological parameters and survival rate were analyzed retrospectively. The ratio between groups was compared by chi-square test. Kaplan-Meier method was used for survival analysis and COX regression model was used for multivariate analysis. Among 100 cases, 71 were males and 29 females; there were 5 cases of stageⅠ, 4 cases of stageⅡ, 19 cases of stage Ⅲ, 65 cases of stage Ⅳ and 7 cases of stage Ⅳs. Ten out of 62 cases (16%) were N-MYC amplified; 15 cases were in low-risk group, 18 were in medium-risk group and 67 were in high-risk group. The positive rate of PD-L1 in NB tumor tissue was 57% (57/100), of which 55 were weakly positive, 1 was moderately positive and 1 was strongly positive. The positive rates of PD-L1 expression in tumor tissues without bone metastasis were higher than those with bone metastasis(66%(39/59).44%(18/41), χ(2)=4.864, 0.027), the positive rates of PD-L1 expression in tumor tissues pathologically diagnosed as neuroblastoma were higher than those pathologically diagnosed as ganglioneuroblastoma (61%(53/87) .31%(4/13), χ(2)=4.195, 0.041), the positive rates of PD-L1 expression in tumor tissues originated from abdominal cavity were higher than those originated from other places (61% (51/83)35%(6/17), χ(2)=3.937,0.047).The 4-year event-free survival (EFS) rates of patients with PD-L1 negative and positive were 40% and 33% (χ(2)=0.009, 0.923), respectively. The 4-year overall survival (OS) rates of patients with PD-L1 negative and positive were 62% and 58% (χ(2)=0.294, 0.587). Among 33 non-high-risk patients, the 4-year EFS rates of patients with PD-L1 negative and positive were 89% and 78% (χ(2)=0.001, 0.965), the 4-year OS rates of patients with PD-L1 negative and positive were 100% and 96% (χ(2)=0.500, 0.480). Among 67 high-risk patients, the 4-year EFS rates of patients with PD-L1 negative and positive were 24% and 11% (χ(2)=1.154, 0.282), the 4-year OS rates of patients with PD-L1 negative and positive were 48% and 41% (χ(2)=0.692, 0.405). Multivariate analysis showed that N-MYC gene amplification was an independent adverse prognostic factor for OS and EFS rates of NB patients (: 1.726,95:1.209-2.466; :1.326,95:1.014-1.736) and advanced clinical stage was an independent adverse prognostic factor for EFS rates of NB patients (: 26.498, 95:3.518-199.614). The expression of PD-L1 in NB tumor tissues was correlated with the clinical characteristics of children. However, there were no significant differences in the prognosis of patients with or without PD-L1 expression.
探讨神经母细胞瘤(NB)组织中程序性细胞死亡配体1(PD-L1)的表达与患儿临床特征及预后的关系。收集2000年1月至2015年12月在中山大学肿瘤防治中心新诊断的100例NB患儿的临床资料及手术组织石蜡块,回顾性分析PD-L1的表达水平及其与病理参数和生存率的关系。组间比例比较采用卡方检验。生存分析采用Kaplan-Meier法,多因素分析采用COX回归模型。100例患儿中,男71例,女29例;Ⅰ期5例,Ⅱ期4例,Ⅲ期19例,Ⅳ期65例,Ⅳs期7例。62例中有10例(16%)N-MYC扩增;低危组15例,中危组18例,高危组67例。NB肿瘤组织中PD-L1阳性率为57%(57/100),其中弱阳性55例,中度阳性1例,强阳性1例。无骨转移肿瘤组织中PD-L1表达阳性率高于有骨转移者(66%(39/59),44%(18/41),χ² = 4.864,P = 0.027),病理诊断为神经母细胞瘤的肿瘤组织中PD-L1表达阳性率高于神经节神经母细胞瘤(61%(53/87),31%(4/13),χ² = 4.195,P = 0.041),起源于腹腔的肿瘤组织中PD-L1表达阳性率高于其他部位(61%(51/83),35%(6/17),χ² = 3.937,P = 0.047)。PD-L1阴性和阳性患儿的4年无事件生存率(EFS)分别为40%和33%(χ² = 0.009,P = 0.923)。PD-L1阴性和阳性患儿的4年总生存率(OS)分别为62%和58%(χ² = 0.294,P = 0.587)。33例非高危患儿中,PD-L1阴性和阳性患儿的4年EFS分别为89%和78%(χ² = 0.001,P = 0.965),4年OS分别为100%和96%(χ² = 0.500,P = 0.480)。67例高危患儿中,PD-L1阴性和阳性患儿的4年EFS分别为24%和11%(χ² = 1.154,P = 0.282),4年OS分别为48%和41%(χ² = 0.692,P = 0.405)。多因素分析显示,N-MYC基因扩增是NB患儿OS和EFS的独立不良预后因素(HR = 1.726,95%CI:1.209 - 2.466;HR = 1.326,95%CI:1.014 - 1.736),临床分期晚是NB患儿EFS 的独立不良预后因素(HR = 26.498,95%CI:3.518 - 199.614)。NB肿瘤组织中PD-L1的表达与患儿临床特征相关。然而,PD-L1表达阳性和阴性患儿的预后无显著差异。