Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
Molecular Diagnostics, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India.
J Clin Pathol. 2022 Jun;75(6):405-409. doi: 10.1136/jclinpath-2021-207408. Epub 2021 Mar 22.
Anaplastic lymphoma kinase () rearranged non-small cell lung carcinoma (NSCLC) is a distinct molecular subtype and rapid approval of tyrosine kinase inhibitors (TKIs) has necessitated rapid and sensitive diagnostic modalities for the detection of this alteration. Gene rearrangements can be identified using many techniques including fluorescence in situ hybridisation (FISH), reverse transcriptase-PCR, next-generation sequencing (NGS) and immunohistochemistry (IHC) for fusion oncoprotein expression. We aimed to determine the concordance between IHC, FISH and NGS for biomarker detection, and determine differences in sensitivity, and survival outcomes.
We analysed the concordance between IHC using D5F3 monoclonal antibody, FISH (break-apart) and NGS using a custom panel containing 71 different variants.
Among 71 cases included in this study, FISH was evaluable in 58 cases. The concordance of ALK IHC with FISH was 75.9% and that with NGS was 84.5%. The sensitivities of FISH and NGS were 75.6% and 87.5%, respectively. The median progression-free survival of ALK IHC-positive and FISH-negative group was 5.5 months and that of both positive was 9.97 months.
Although NGS offers a better throughput and visualisation, IHC still remains the quintessential screening tool in upfront diagnosis of ALK rearranged NSCLC.
间变性淋巴瘤激酶 () 重排非小细胞肺癌 (NSCLC) 是一种独特的分子亚型，酪氨酸激酶抑制剂 (TKI) 的快速批准使得快速灵敏的诊断方法成为检测这种改变的必要手段。基因重排可以通过多种技术来识别，包括荧光原位杂交 (FISH)、逆转录聚合酶链反应 (RT-PCR)、下一代测序 (NGS) 和免疫组织化学 (IHC) 用于融合癌蛋白表达。我们旨在确定 IHC、FISH 和 NGS 用于生物标志物检测的一致性，并确定敏感性和生存结果的差异。
我们分析了使用 D5F3 单克隆抗体的 IHC、FISH（分离）和使用包含 71 种不同变体的定制面板的 NGS 之间的一致性。
在这项研究中包括的 71 例病例中，58 例可评估 FISH。ALK IHC 与 FISH 的一致性为 75.9%，与 NGS 的一致性为 84.5%。FISH 和 NGS 的灵敏度分别为 75.6%和 87.5%。ALK IHC 阳性和 FISH 阴性组的中位无进展生存期为 5.5 个月，两者均为阳性的为 9.97 个月。
尽管 NGS 提供了更好的通量和可视化，但 IHC 仍然是 ALK 重排 NSCLC 初始诊断的基本筛选工具。
