Comparison of detection methods and follow-up study on the tyrosine kinase inhibitors therapy in non-small cell lung cancer patients with ROS1 fusion rearrangement
Comparison of detection methods and follow-up study on the tyrosine kinase inhibitors therapy in non-small cell lung cancer patients with ROS1 fusion rearrangement
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DOI：
10.1186/s12885-016-2582-9
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发表时间：
2016-08-04
期刊：
影响因子：
3.8
通讯作者：
Gu, Xia
中科院分区：
文献类型：
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作者：
Wu, Jieyu;Lin, Yunen;Gu, Xia
背景：ROS原癌基因1受体酪氨酸激酶(ROS1)融合重排的筛选可能有助于非小细胞肺癌(NSCLC)的有效治疗。然而，三种主要的ROS1重排检测方法都有局限性，目前还没有检测非小细胞肺癌ROS1重排的常规方法。本研究的目的是比较免疫组织化学(IHC)、荧光原位杂交(FISH)和定量实时聚合酶链式反应(qRT-PCR)检测非小细胞肺癌中ROS1重排的能力，并探讨ROS1重排患者的临床特征和组织病理学特征。此外，我们还观察了酪氨酸激酶抑制剂(TKIs)对ROS1重排和晚期疾病(III b-IV)患者的治疗效果。用D4D6单抗在IHC全自动检测仪上进行IHC检测，并用FISH和qRT-PCR对检测结果进行验证。对FISH和qRT-PCR阳性病例进行直接测序。结果：本研究共纳入238例晚期非小细胞肺癌患者。10例患者检测到ROS1重排。FISH和qRT-PCR结果的符合率为100%，而当IHC表现为弥漫的(~gt；=60%的肿瘤细胞)2-3+细胞质反应模式时，FISH和IHC结果高度一致。携带ROS1重排的患者多为年轻人(8/10)、女性(7/10)和非吸烟者(7/10)合并腺癌(10/10)和腺泡型。肿瘤多为中等级别(6/8)。结论：IHC、FISH和qRT-PCR能可靠地检测NSCLC中ROS1重排，IHC可作为一种初步的筛查工具。这些结果支持了ROS1 TKI治疗伴有ROS1重排的晚期非小细胞肺癌患者的疗效。
Background: The screening of ROS proto-oncogene 1, receptor tyrosine kinase(ROS1) fusion rearrangement might be potentially beneficial for an effective therapy against non-small cell lung cancer (NSCLC). However, the three main ROS1 rearrangement detection methods have limitations, and no routine protocol for the detection of ROS1 rearrangement in NSCLC is available. In this study, our aims were to compare immunohistochemistry (IHC), fluorescent in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (qRT-PCR) in their ability to detect ROS1 rearrangement in NSCLC, and discuss the clinical characteristics and histopathology of the patients with ROS1 rearrangement. Moreover, the effects of tyrosine kinase inhibitors (TKIs) therapy on the patients with ROS1 rearrangement and advanced stage disease (III b-IV) were investigated.Methods: Patients with a previously diagnosed NSCLC were recruited in this study from November 2013 to October 2015. IHC was performed using the D4D6 monoclonal antibody (mAb) in an automatic IHC instrument, while FISH and qRT-PCR were carried out to confirm the IHC results. FISH and qRT-PCR positive cases underwent direct sequencing. After detection, patients with advanced ROS1 rearranged NSCLC had received TKI therapy.Results: Two hundred and thirty-eight patients were included in this study. ROS1 rearrangement was detected in 10 patients. The concordant rate of FISH and qRT-PCR results was 100 %, while in the FISH and IHC results high congruence was present when IHC showed a diffusely (>= 60 % tumor cells) 2-3+ cytoplasmic reactivity pattern. Patients harboring ROS1 rearrangement were mostly young (8/10), females (7/10) and non-smokers (7/10) with adenocarcinoma (10/10) and acinar pattern. Most of their tumor were in intermediate grade (6/8). Among these 10 patients, three of them in stage IV with ROS1 rearrangement gained benefits from ROS1 TKI therapy.Conclusions: IHC, FISH and qRT-PCR can reliably detect ROS1 rearrangement in NSCLC, while IHC can be used as a preliminary screening tool. These results supported the efficacy of ROS1 TKI therapy in treating advanced NSCLC patients with ROS1 rearrangement.