Institute for Research on Cancer and Ageing (IRCAN), INSERM U1081, CNRS UMR 7284, Team 3, Nice; Team 3, Faculty of Medicine, University of Nice Sophia Antipolis, Nice; Human Biobank Unit; Laboratory of Clinical and Experimental Pathology, University Hospital Centre of Nice, Pasteur Hospital, Nice; Cancéropôle PACA, Marseille.
Institute for Research on Cancer and Ageing (IRCAN), INSERM U1081, CNRS UMR 7284, Team 3, Nice; Team 3, Faculty of Medicine, University of Nice Sophia Antipolis, Nice; Laboratory of Clinical and Experimental Pathology, University Hospital Centre of Nice, Pasteur Hospital, Nice.
Ann Oncol. 2012 Nov;23(11):2907-2913. doi: 10.1093/annonc/mds137. Epub 2012 Jun 26.
A subgroup of anaplastic lymphoma kinase (ALK)-rearranged lung tumours can respond to ALK inhibitors. Until now, the ALK status in circulating tumour cells (CTCs) isolated from patients with lung cancer has not been characterised. We assessed the ALK status in CTCs detected in patients with lung cancer and correlated the results to the ALK status defined in the corresponding tumour tissue.
A total of 87 patients with lung adenocarcinoma showing CTCs isolated using the isolation by size of epithelial tumour cell method were screened for their ALK status both in tumour samples and in CTCs. ALK break-apart fluorescence in situ hybridisation (FISH) and immunoreactivity analyses using an anti-ALK antibody (5A4 clone) were carried out on CTCs and compared with the results obtained in the corresponding tissue specimens.
A total of five patients showed ALK-gene rearrangement and strong ALK protein expression in CTCs and in the corresponding tumour samples. Both ALK-FISH and ALK immunoreactivity analyses show negative results in CTCs and corresponding tumour samples for 82 patients. Conclusions We demonstrated that the ALK status can be determined in CTCs isolated from patients with lung cancer by immunocytochemistry and FISH analyses. These results favour non-invasive, ALK-gene status pre-screening on a routine basis on CTCs isolated from patients with lung cancer and open new avenues for real-time monitoring for adapted targeted therapy.
间变性淋巴瘤激酶(ALK)重排的肺肿瘤亚组可以对 ALK 抑制剂产生应答。到目前为止,尚未对从肺癌患者中分离出的循环肿瘤细胞(CTC)中的 ALK 状态进行特征描述。我们评估了肺癌患者 CTC 中检测到的 ALK 状态,并将结果与相应肿瘤组织中定义的 ALK 状态相关联。
总共筛选了 87 例显示使用大小分离上皮肿瘤细胞法分离出 CTC 的肺腺癌患者,以确定其肿瘤样本和 CTC 中的 ALK 状态。对 CTC 进行 ALK 断裂分离荧光原位杂交(FISH)和使用抗 ALK 抗体(5A4 克隆)的免疫反应性分析,并与相应组织标本的结果进行比较。
共有 5 例患者的 CTC 和相应肿瘤样本中显示出 ALK 基因重排和强烈的 ALK 蛋白表达。82 例患者的 CTC 和相应肿瘤样本的 ALK-FISH 和 ALK 免疫反应性分析均显示为阴性。
我们证明了通过免疫细胞化学和 FISH 分析可以确定从肺癌患者中分离出的 CTC 中的 ALK 状态。这些结果支持对肺癌患者的 CTC 进行非侵入性、ALK 基因状态常规预筛选,并为实时监测适应性靶向治疗开辟了新途径。