神经母细胞瘤组织中B7H3的表达及临床意义

Expression and clinical significance of B7H3 in neuroblastoma tissues

目的探讨神经母细胞瘤肿瘤组织B7H3的表达与患者临床特点及预后关系。方法收集2000年1月至2015年12月经中山大学肿瘤防治中心收治的100例神经母细胞瘤患者的临床资料及病理蜡块,采用免疫组织化学法检测B7H3在肿瘤组织的表达并进行统计分析。结果1.B7H3在肿瘤组织阳性率为79%(79/100例),其中弱阳性37例,中度阳性31例,强阳性11例,58%为低表达,42%为高表达。2.B7H3的阳性率与患者的危险度分层、年龄、分期、原发灶部位、N-MYC基因状态均呈正相关(r=0.621、0.350、0.730、0.224、0.335,均P<0.05)。3.B7H3的高表达率与患者的危险度、分期、N-MYC基因状态、瘤灶最大直径均呈正相关(r=0.177、0.016、0.175、0.284,均P<0.05)。4.100例患者,B7H3阴性和阳性的4年无事件生存(EFS)率分别为89.5%和19.9%(χ^2=31.260,P<0.001),4年总生存(OS)率分别为94.7%和48.3%(χ^2=20.212,P<0.001);33例非高危患者中B7H3阴性和阳性的4年EFS率分别为100.0%和47.3%(χ^2=8.760,P=0.003),4年OS率分别为100.0%和93.8%(χ^2=1.063,P=0.303);67例高危患者B7H3阴性和阳性4年EFS率分别为50.0%和15.4%(χ^2=4.093,P=0.043),4年OS率分别为75.0%和42.0%(χ^2=1.872,P=0.171)。5.100例患儿,B7H3低表达和高表达的NB患儿4年EFS率分别为41.8%和27.1%(χ^2=3.801,P=0.051),4年OS率分别为58.6%和63.8%(χ^2=0.111,P=0.739);33例非高危患者中B7H3低表达和高表达的4年EFS率分别为94.7%和44.2%(χ^2=9.122,P=0.003),4年OS率分别为100.0%和90.9%(χ^2=2.000,P=0.157);67例高危患者中,低表达与高表达的患儿4年EFS率分别为13.9%和22.1%(χ^2=0.061,P=0.805),4年OS率分别为36.3%和57.7%(χ^2=2.060,P=0.151)。6.多因素分析显示B7H3阳性患儿的OS率和EFS率均较B7H3阴性患儿低[RR 95%CI:28.110(2.430~325.148),P=0.008;RR 95%CI:12.834(2.669~61.715),P=0.001]。结论神经母细胞瘤肿瘤组织中B7H3的阳性率高,B7H3表达水平与患儿临床特点密切相关。肿瘤组织中B7H3阳性是影响患儿的独立不良预后因素,B7H3可能作为NB的预后指标之一。

Objective To investigate the expression of B7H3 in neuroblastoma (NB) tissues and its relationship between clinical characteristics and prognosis of patients. MethodsThe clinical data and pathological wax of 100 cases with neuroblastoma admitted from January 2000 to December 2015 in Sun Yet-Sen University Cancer Center were collected.The expression of B7H3 in tumor tissues was detected by immunohistochemistry (IHC) and then the expression of B7H3 and its relation to pathological parameters and survival rate of patients were analyzed. Results(1) The positive rates of B7H3 in tumor tissues were 79%(79/100 cases), of which 37 were weak positive, 31 were mode-rate positive, 11 were strong positive, 58%(58/100 cases) showed low expression and 42%(42/100 cases) showed high expression.(2)The positive rate of B7H3 was positively correlated with the risk stratification, age, stage, primary site and N-MYC gene status (r=0.621, 0.350, 0.730, 0.224, 0.335;all P<0.05).(3)The high expression rates of B7H3 were positively correlated with the risk, stage, N-MYC gene status and tumor size (r=0.177, 0.016, 0.175, 0.284;all P<0.05).(4)B7H3 negative and positive 4-year event free survival (EFS) rates of 100 patients were 89.5% and 19.9%(χ^2=31.260, P<0.001), 4-year overall survival(OS) rates were 94.7% and 48.3%(χ^2=20.212, P<0.001), for 33 non-high-risk patients, B7H3 negative and positive 4-year EFS rates were 100.0% and 47.3%(χ^2=8.760, P=0.003), and 4-year OS rates were 100.0% and 93.8%(χ^2=1.063, P=0.003), respectively.Sixty-seven high-risk patients with B7H3 negative and positive 4-year EFS were 50.0% and 15.4%(χ^2=4.093, P=0.043), 4-year OS were 75.0% and 42.0%, respectively (χ^2=1.872, P=0.171).(5)The 4-year EFS rates of 100 patients with B7H3 low expression and high expression were 41.8% and 27.1%(χ^2=3.801, P=0.051), and 4-year OS rates were 58.6% and 63.8%(χ^2=0.111, P=0.739), respectively.The 4-year EFS and OS rates for 33 non-high-risk patients with B7H3 low expression and high expression were 94.7% and 44.2%(χ^2=9.122, P=0.003), 100.0% and 90.9%(χ^2=2.000, P=0.157), respectively.The 4-year EFS and OS rates of 67 high-risk patients with high expression and low expression of B7H3 were 13.9% and 22.1%(χ^2=0.061, P=0.805), 36.3% and 57.7%(χ^2=2.060, P=0.151), respectively.(6)Multivariate analysis showed that OS and EFS in B7H3 positive patients were lower than those in B7H3 negative patients[RR 95%CI: 28.110 (2.430-325.148);P=0.008;RR 95%CI: 12.834 (2.669-61.715), P=0.001]. ConclusionsThe positive rate of B7H3 in neuroblastoma is high, and the expression level of B7H3 is closely related to the clinical characteristics of the patients.Positive B7H3 in tumor tissues is an independent poor prognostic factor.B7H3 may be one of the new prognostic indicators for NB.