四种技术平台检测甲状腺癌NTRK融合变异的比较  

Comparative study of four technology platforms for detection of thyroid carcinoma NTRK fusion gene

作　　者：陈灵锋[1] 林洁[1] 俞训彬[1] 吴义娟 游治杰 陈小岩[1] CHEN Lingfeng;LIN Jie;YU Xunbin;WU Yijuan;YOU Zhijie;CHEN Xiaoyan(Shengli Clinical Medical College of Fujian Medical University/Department of Pathology,Fujian Provincial Hospital,Fuzhou 350001,China)

机构地区：[1]福建医科大学省立临床医学院/福建省立医院病理科,福州350001

出　　处：《临床与实验病理学杂志》2023年第12期1470-1475,共6页Chinese Journal of Clinical and Experimental Pathology

基　　金：福建省自然科学基金面上项目(2018J01251)。

摘　　要：目的探讨免疫组化、DNA-based NGS、FISH和qRT-PCR四种技术平台检测甲状腺癌NTRK融合变异的一致性。方法对40例临床组织样本(其中31例为甲状腺癌样本)同时行FISH、免疫组化、DNA-based NGS和qRT-PCR法检测NTRK融合基因。结果四种技术平台均检测的31例甲状腺癌样本中,与FISH技术相比,免疫组化的敏感性、特异性、阳性预测值(positive predictive value,PPV)、阴性预测值(negative predictive value,NPV)和总符合率(total coincidence rate,TCR)分别为100%(9/9)、90.9%(20/22)、81.8%(9/11)、100%(20/20)、93.5%(29/31),其PPV较差;DNA-based NGS的敏感性、特异性、PPV、NPV和TCR分别为44.4%(4/9)、100%(22/22)、100%(4/4)、81.5%(22/27)、83.9%(26/31),其敏感性较差;qRT-PCR和FISH技术检测的一致性为100%(31/31)。与FISH技术相比,免疫组化、DNA-based NGS和qRT-PCR的Kappa值分别为0.853、0.532和1.000。在40例临床组织样本中,39例与FISH结果一致,仅1例(脂肪纤维瘤病样神经肿瘤)因检测范围未覆盖NTRK的少见融合类型(LMNA:exon4-NTRK1:exon10)qRT-PCR法未检出,基于RNA检测融合的qRT-PCR与FISH技术的符合率最高。结论基于RNA的qRT-PCR技术具有敏感性高、特异性高,操作便捷、判读简易的特性,可能是适用于病理科常规临床检测甲状腺癌NTRK融合变异的优选方案。Purpose To study the consistency of NTRK fusion gene in the thyroid carcinoma detected by four technology platforms:immunohistochemistry,DNA-based NGS,FISH and qRT-PCR.Methods NTRK fusion gene was detected by FISH,immunohistochemical(IHC),DNA-based NGS and qRT-PCR in a same group of 40 clinical cases(among them,31 cases were thyroid cancer samples).Results In a group of 31 thyroid cancer cases detected by four techniques,compared with FISH,the sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and total coincidence rate(TCR)of IHC was 100%(9/9),90.9%(20/22),81.8%(9/11),100%(20/20),93.5%(29/31),respectively.The PPV of IHC was poor.The sensitivity,specificity,PPV,NPV and TCR of DNA-based NGS was 44.4%(4/9),100%(22/22),100%(4/4),81.5%(22/27),83.9%(26/31),respectively,and the sensitivity was poor.The TCR of qRT-PCR was 100%(31/31).Compared with FISH,Kappa value of IHC,DNA-based NGS and qRT-PCR was 0.853,0.532 and 1.000,respectively.Of the 40 clinical cases,the concordance between qRT-PCR and FISH was observed for 39 samples,for the qRT-PCR assay did not cover the NTRK fusion type(LMNA:exon4-NTRK1:exon10).Compared with FISH,the coincidence rate of qRT-PCR was highest.Conclusion The RNA-based assay of qRT-PCR does have the advantages of high sensitivity and high specificity,and may be an optimal scheme for routine clinical detection of NTRK fusion variation in thyroid cancer in pathology department.

关 键 词：甲状腺肿瘤 NTRK 基因融合 QRT-PCR 

分 类 号：R736.1[医药卫生—肿瘤]