Abstract：
Non-small cell lung carcinoma (NSCLC) patients with BRAF V600E-mutated tumors respond to targeted therapy. Testing for BRAF V600E is commonly performed with molecular methods; however, a mutation-specific VE1 antibody clone can provide an alternative testing option using immunohistochemistry (IHC) for practices using single-gene testing and in situations when the specimen is inadequate for molecular testing. This study evaluates the usefulness of VE1 IHC in screening for BRAF V600E mutations in NSCLC cytology specimens.
The authors retrospectively identified cytology cases with a diagnosis of NSCLC that had BRAF V600E IHC performed on cell block sections with the monoclonal VE1 antibody clone. The BRAF V600E IHC results were compared with those of molecular testing performed with an amplicon-based next-generation sequencing assay.
There were 201 NSCLC cases evaluated. The VE1 IHC was positive in seven of seven BRAF V600E-mutated tumors (100%) and was negative in 158 of 158 nonmutated BRAF V600E tumors (100%). Thirty cases did not undergo molecular testing, primarily because of insufficient tissue or because molecular testing was performed on an alternative specimen. Six cases showed equivocal weak/focal staining: Two cases demonstrated BRAF V600E mutations, and four cases were negative by molecular testing.
This study suggests that BRAF V600E IHC can be used reliably to screen NSCLC cytology specimens, and negative results strongly indicate the absence of a BRAF V600E mutation. Having a low threshold for equivocal staining is recommended with molecular confirmation of BRAF V600E for any cases demonstrating weak and/or focal cytoplasmic staining.
The authors retrospectively identified cytology cases with a diagnosis of NSCLC that had BRAF V600E IHC performed on cell block sections with the monoclonal VE1 antibody clone. The BRAF V600E IHC results were compared with those of molecular testing performed with an amplicon-based next-generation sequencing assay.
There were 201 NSCLC cases evaluated. The VE1 IHC was positive in seven of seven BRAF V600E-mutated tumors (100%) and was negative in 158 of 158 nonmutated BRAF V600E tumors (100%). Thirty cases did not undergo molecular testing, primarily because of insufficient tissue or because molecular testing was performed on an alternative specimen. Six cases showed equivocal weak/focal staining: Two cases demonstrated BRAF V600E mutations, and four cases were negative by molecular testing.
This study suggests that BRAF V600E IHC can be used reliably to screen NSCLC cytology specimens, and negative results strongly indicate the absence of a BRAF V600E mutation. Having a low threshold for equivocal staining is recommended with molecular confirmation of BRAF V600E for any cases demonstrating weak and/or focal cytoplasmic staining.
摘要：
背景：患有BRAFV600E突变肿瘤的非小细胞肺癌（NSCLC）患者对靶向治疗有反应。BRAFV600E的测试通常使用分子方法进行；然而，突变特异性VE1抗体克隆可以使用免疫组织化学(IHC)为使用单基因检测的实践和样本不足以进行分子检测的情况提供替代检测选择.这项研究评估了VE1IHC在筛选NSCLC细胞学标本中BRAFV600E突变中的有用性。
方法：作者回顾性鉴定了诊断为非小细胞肺癌的细胞学病例，对单克隆VE1抗体克隆的细胞块切片进行了BRAFV600EIHC。将BRAFV600EIHC结果与使用基于扩增子的下一代测序测定进行的分子测试的结果进行比较。
结果：评估了201例NSCLC。VE1IHC在七个BRAFV600E突变的肿瘤中的七个（100％）为阳性，而在158个未突变的BRAFV600E肿瘤中的158个（100％）为阴性。30例没有进行分子检测,主要是因为组织不足或因为对替代标本进行了分子检测。6例显示模棱两可的弱/局灶性染色：2例显示BRAFV600E突变，4例分子检测呈阴性。
结论：这项研究表明，BRAFV600EIHC可以可靠地用于筛选NSCLC细胞学标本，阴性结果强烈表明不存在BRAFV600E突变。对于任何证明弱和/或局灶性细胞质染色的病例，建议使用BRAFV600E分子确认具有低阈值的模棱两可染色。
方法：作者回顾性鉴定了诊断为非小细胞肺癌的细胞学病例，对单克隆VE1抗体克隆的细胞块切片进行了BRAFV600EIHC。将BRAFV600EIHC结果与使用基于扩增子的下一代测序测定进行的分子测试的结果进行比较。
结果：评估了201例NSCLC。VE1IHC在七个BRAFV600E突变的肿瘤中的七个（100％）为阳性，而在158个未突变的BRAFV600E肿瘤中的158个（100％）为阴性。30例没有进行分子检测,主要是因为组织不足或因为对替代标本进行了分子检测。6例显示模棱两可的弱/局灶性染色：2例显示BRAFV600E突变，4例分子检测呈阴性。
结论：这项研究表明，BRAFV600EIHC可以可靠地用于筛选NSCLC细胞学标本，阴性结果强烈表明不存在BRAFV600E突变。对于任何证明弱和/或局灶性细胞质染色的病例，建议使用BRAFV600E分子确认具有低阈值的模棱两可染色。
