联合IDH1、1p/19q和ATRX对胶质瘤分子分型的临床意义  

Clinical Significance of Combination of IDH1,1p/19q and ATRX in Molecular Typing of Glioma

作　　者：朱文标[1] 卢善明[1] 李海南 罗文娟 肖焕钦 谢寿城[1] 刘晋发 ZHU Wen-biao;LU Shan-ming;LI Hai-nan;LUO Wen-juan;XIAO Huan-qin;XIE Shou-cheng;LIU Jin-fa(Department of Pathology,Meizhou People’s Hospital,Meizhou 514031,China;Department of Pathology,Guangdong 999 Brain Hospital,Guangzhou 510510,China)

机构地区：[1]梅州市人民医院病理科,广东梅州514031 [2]广东三九脑科医院病理科,广州510510

出　　处：《南昌大学学报（医学版）》2020年第4期41-45,共5页Journal of Nanchang University：Medical Sciences

基　　金：梅州市科技计划项目(2017B015)。

摘　　要：目的探讨联合异柠檬酸脱氢酶1(IDH1)、1号染色体短臂和19号染色体长臂(1p/19q)和α-地中海贫血/智力低下综合征X染色体连锁基因(ATRX)对胶质瘤分子分型的临床意义。方法回顾经术后病理证实的104例胶质瘤患者的临床及组织病理资料,采用免疫组织化学法对其存档病理组织蜡块进行IDH1突变、ATRX表达缺失检测,采用荧光原位杂交法检测1p/19q缺失情况,通过门诊复查和电话等方式随访患者的术后生存情况,联合IDH1、1p/19q和ATRX将胶质瘤患者进行分子分型(A型:IDH1突变,1p/19q缺失;B型:IDH1突变,1p/19q完整;C型:IDH1野生,ATRX突变;D型:IDH1野生,ATRX野生),并分析不同分子分型患者临床病理特征及预后间的差异。结果联合分子分型与胶质瘤患者的年龄、组织学分级、卡氏功能状态(KPS)评分与病理分型均有关(P<0.05),其中与病理学分型的相关性最大,而与性别、肿瘤部位和肿瘤大小无关(P>0.05)。Kaplan-Meier生存分析结果显示,4组分子分型的胶质瘤患者术后总生存期差异显著(Log-Rank:χ2=31.631,P<0.001),其中B型患者的中位生存期最长,D型患者中位生存期最短。COX风险回归分析显示,胶质瘤患者的预后与患者年龄、组织学分级、KPS评分、病理分型、IDH1、ATRX、联合分子分型和治疗方案均独立相关(P<0.05),而与患者性别、肿瘤部位、大小和1p/19q缺失无关(P>0.05)。结论联合IDH1突变、1p/19q杂合缺失和ATRX突变对胶质瘤患者进行分子分型,有助于临床诊断,还可能为患者术后生存情况提供参考。Objective To investigate the clinical significance of combination of isocitratedehydrogenase 1(IDH1),deletion of short arm of chromosome 1 and long arm of chromosome 19(1p/19q)and X-linkedα-thalassemia/mental retardation syndrome(ATRX)in molecular typing of glioma.Methods The clinical and histopathological data of 104 patients with glioma confirmed by postoperative pathology were reviewed.IDH1 mutation and ATRX expression deletion were measured by immunohistochemistry.The deletion of 1p/19q was detected by fluorescence in situ hybridization.The postoperative survival of patients was followed up by outpatient reexamination and telephone.The combination of IDH,1p/19q and ATRX was used for molecular typing of glioma(type A:IDH1 mutation,1p/19q deletion;type B:IDH1 mutation,1p/19q integrity;type C:IDH1 wild-type,ATRX mutation;type D:IDH1 wild-type,ATRX wild-type).The differences in clinicopathological characteristics and prognosis were analyzed among patients with different molecular types.Results The combined molecular typing was related to age,histological grade,Kamofsky performance status(KPS)score and pathological classification(especially pathological classification)(P<0.05),but was not correlated with gender,tumor location and tumor size(P>0.05).Kaplan-Meier survival analysis showed that there were significant differences in the total survival time among patients with different molecular types of glioma(Log-Rank:χ2=31.631,P<0.001).Type B patients had the longest median survival and type D patients had the shortest median survival.COX risk regression analysis showed that the prognosis of glioma patients was independently correlated with age,histological grade,KPS score,pathological classification,IDH1,ATRX,combined molecular typing and treatment regimen(P<0.05),but was not related to gender,tumor location,tumor size and 1p/19q deletion(P>0.05).Conclusion The combination of IDH1 mutation,1p/19q loss of heterozygosity and ATRX mutation is helpful for clinical diagnosis and may also be used as molecular indicator

关 键 词：胶质瘤 异柠檬酸脱氢酶1 1号染色体短臂和19号染色体长臂缺失 α-地中海贫血/智力低下综合征X染色体连锁基因 

分 类 号：R739.4[医药卫生—肿瘤]