广谱Trk免疫组化标志物的检测可高效及准确筛查NTRK融合基因
  ——本文经《美国外科病理学杂志》授权发布,其他媒体转载或引用须经《美国外科病理学杂志》同意,否则追究法律责任。

  活化性神经营养酪氨酸受体激酶(neurotrophic tyrosine receptor kinase,NTRK)融合基因通常采用基于核酸的检测技术,可高度定位和定义某些肿瘤。本研究探讨了广谱Trk免疫组化标志物(pan-Trk)检测NTRK融合基因的能力。预期采用基于DNA的新一代测序技术MSK-IMPACT检测NTRK融合基因。对于新发现的NTRK融合基因,进一步采用Archer Dx融合检测试剂盒检测NTRK融合型转录本。后续采用pan-Trk单克隆抗体(mAb EPR17341)对全部NTRK融合基因阳性病例和20例经Archer方法确认NTRK融合基因阴性对照病例进行免疫组化检测。23例NTRK融合基因阳性病例中,15例为已知类型的活化型NTRK融合基因,8例为新发现功能意义不明的NTRK融合基因;后者中6例经Archer方法检测存在NTRK融合基因转录本。全部21例经Archer方法确认存在NTRK融合基因转录本病例中,20例pan-Trk免疫组化检测阳性。1例免疫组化阴性者为存在错配修复基因缺陷并携带ETV6-NTRK3 融合基因的结直肠癌患者。20例阴性对照病例与pan-Trk免疫组化检测结果一致。Pan-Trk免疫组化检测可转录NTRK融合基因的敏感性和特异性分别为95.2%和100%。Pan-Trk免疫组化标志物常规表达模式为细胞浆着色,但5例LMNA-NTRK1融合基因阳性病例同时呈现核膜聚集而深染的表达模式,4例TPM3/4融合基因阳性病例同时呈现细胞膜聚集而深染的表达模式,半数(6例中的3例)ETV6-NTRK3融合基因阳性病例同时呈现核着色。Pan-Trk免疫组化检测方法是一种快速且节省样本的NTRK融合基因筛查方法,特别是对驱动基因阴性的晚期恶性肿瘤、潜在NTRK融合基因检出率高的分泌性癌及先天性纤维肉瘤更有意义。Pan-Trk免疫组化标志物的检测可以帮助确定新发现的NTRK融合基因是否存在转录本。
Am J Surg Pathol 2017;41:1547–1551
美国外科病理学杂志中文版2018年第一期摘要No.8
(颜黎栩 翻译 刘艳辉 审校)
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