ROS1 immunohistochemistry among major genotypes of non-small-cell lung cancer.
ROS1 immunohistochemistry among major genotypes of non-small-cell lung cancer.
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DOI：
10.1016/j.cllc.2014.10.003
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发表时间：
2015-03
影响因子：
3.6
通讯作者：
Hirsch FR
中科院分区：
文献类型：
--
作者：
Boyle TA;Masago K;Ellison KE;Yatabe Y;Hirsch FR
在肺癌患者中识别ROS1重排使他们能够从靶向治疗中获益。我们比较了免疫组化（IHC）与更繁琐的方法，如荧光原位杂交和逆转录聚合酶链反应，以确定肺腺癌患者（n = 33）的ROS1重排。我们的研究结果表明，免疫组化是一种敏感（100%）和特异性（100%）的方法来确定肺癌患者的ROS1重排。ROS1基因融合通过组成性激活ROS1酪氨酸激酶受体而导致几种癌症。ROS1靶向抑制剂治疗可提高约1%至2%的ROS1基因融合肺腺癌患者的生存率。虽然荧光原位杂交（FISH）是检测ROS1重排的标准诊断程序，我们研究了免疫组织化学（IHC）。对33份肺腺癌全组织标本的选定队列进行了ROS1 IHC，通过逆转录酶-聚合酶链反应（RT-PCR）和FISH检测到EGFR（n = 5）、KRAS（n = 5）、ERBB 2（HER2）（n = 3）、ROS1（n = 6）、ALK（n = 5）和RET（n = 3）基因改变和泛阴性（n = 6）。在33例标本中，6例标本中RT-PCR检测到ROS1基因融合，IHC检测到ROS1蛋白高表达。在这6份标本中，有5份经FISH检测也呈ROS1基因重排阳性。所有27例通过基因检测对ROS1重排呈阴性的肺癌标本都没有或低水平的ROS1蛋白表达。我们优化了ROS1 IHC和评分，为检测整个组织中的ROS1基因重排提供了高灵敏度和特异性。ROS1免疫组化技术是一种经济实用的ROS1基因重排筛查方法。
Identification of ROS1 rearrangements in patients with lung cancer allows them to benefit from targeted therapy. We compared immunohistochemistry (IHC) with more cumbersome methods such as fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction for identification of ROS1 rearrangements in patients with lung adenocarcinoma (n = 33). Our results showed that IHC is a sensitive (100%) and specific (100%) method to identify ROS1 rearrangements in patients with lung cancer. ROS1 gene fusions cause several cancers by constitutively activating the ROS1 tyrosine kinase receptor. ROS1-targeted inhibitor therapy improves survival in the approximately 1% to 2% of patients with lung adenocarcinoma with ROS1 gene fusions. Although fluorescence in situ hybridization (FISH) is the standard diagnostic procedure for detecting ROS1 rearrangements, we studied immunohistochemistry (IHC). ROS1 IHC was performed on a selected cohort of 33 lung adenocarcinoma whole tissue specimens with alterations in the EGFR (n = 5), KRAS (n = 5), ERBB2 (HER2) (n = 3), ROS1 (n = 6), ALK (n = 5), and RET (n = 3) genes and pan-negative (n = 6) detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and FISH. In the cohort of 33 specimens, both ROS1 gene fusion using RT-PCR and high ROS1 protein expression using IHC were detected in 6 specimens. Of these 6 specimens, 5 were also positive by FISH for ROS1 gene rearrangements. All 27 lung cancer specimens that were negative for ROS1 rearrangements by genetic testing had no to low ROS1 protein expression. We have optimized ROS1 IHC and scoring to provide high sensitivity and specificity for detecting ROS1 gene rearrangements in whole tissue. ROS1 IHC could be a practical and cost-effective method to screen for ROS1 gene rearrangements.