通过FISH，IHC和NGS检测ALK以预测克唑替尼在晚期非小细胞肺癌中的获益的比较。,Lung Cancer

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通过FISH，IHC和NGS检测ALK以预测克唑替尼在晚期非小细胞肺癌中的获益的比较。
Lung Cancer ( IF 4.5 ) Pub Date : 2019-03-20 , DOI: 10.1016/j.lungcan.2019.03.018
Chen Lin ₁ , Xun Shi ₁ , Shao Yang ₂ , Jun Zhao ₁ , Qiong He ₁ , Ying Jin ₃ , Xinmin Yu ₄

Affiliation

目的间变性淋巴瘤激酶（ALK）现已成为非小细胞肺癌（NSCLC）中一种经过验证的激酶靶标。我们实施了三种ALK实验室方法：荧光原位杂交（FISH），免疫组织化学（IHC）和下一代测序（NGS）来检测EML4-ALK融合蛋白，并比较了克唑替尼在ALK阳性患者中的疗效预测价值。方法本研究共纳入55例至少采用一种方法确诊的ALK阳性患者，其中45例同时接受FISH，IHC和NGS评估，另外10例仅接受IHC和NGS评估ALK状况。结果IHC的阳性率最高（94.5％），其次是NGS（92.7％）和FISH（82.4％），其中IHC和NGS的最高一致率为87.3％。在ORR中未检测到差异，ALK阳性病例的DCR和PFS分为三组。值得注意的是，与NGS阴性病例相比，NGS阳性患者与更高的DCR和更长的PFS相关（P = 0.02和P = 0.09），而FISH和IHC的状态在预测克唑替尼的预后方面没有区别。TP53并发突变可能会降低对克唑替尼的反应性并恶化ALK重排NSCLC的预后。结论尽管被认为是黄金标准，但鱼呈现出一定的假阴性率。Ventana-D5F3 IHC可作为筛查工具，而NGS阳性则可更准确地预测克唑替尼的临床获益，从而可对特定变体和同时发生的基因组改变进行高效检测。02和P = 0.09），而FISH和IHC状态在预测克唑替尼的预后方面没有区别。TP53并发突变可能会降低对克唑替尼的反应性并恶化ALK重排NSCLC的预后。结论尽管鱼被认为是黄金标准，但仍具有一定的假阴性率。Ventana-D5F3 IHC可作为筛查工具，而NGS阳性则可以更准确地预测克唑替尼的临床获益，从而可以有效测试特定变体和同时发生的基因组改变。02和P = 0.09），而FISH和IHC状态在预测克唑替尼的预后方面没有区别。TP53并发突变可能会降低对克唑替尼的反应性并恶化ALK重排NSCLC的预后。结论尽管鱼被认为是黄金标准，但仍具有一定的假阴性率。Ventana-D5F3 IHC可作为筛查工具，而NGS阳性则可以更准确地预测克唑替尼的临床获益，从而可以有效测试特定变体和同时发生的基因组改变。

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Comparison of ALK detection by FISH, IHC and NGS to predict benefit from crizotinib in advanced non-small-cell lung cancer.

PURPOSE Anaplastic lymphoma kinase (ALK) is now a validated kinase target in non-small cell lung cancer (NSCLC). We implemented three ALK laboratory methodologies: fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and next-generation sequencing (NGS) to detect EML4-ALK fusions and compared the predictive value for Crizotinib efficacy in ALK-positive patients. METHODS 55 ALK positive patients confirmed by at least one method were enrolled in the present study, of whom 45 cases were assessed by FISH, IHC and NGS concurrently, and another 10 cases only received IHC and NGS assessment for ALK status. RESULTS IHC presented the uppermost positive rate (94.5%), followed by NGS (92.7%) and FISH(82.4%), among which IHC and NGS had the highest concordance rate of 87.3%. No difference was detected in ORR, DCR and PFS of ALK positive cases defined in three groups. Notably, NGS positive patients were correlated with a higher DCR and longer PFS compared to NGS negative cases (P = 0.02 and P = 0.09), while FISH and IHC status were not distinguishing in predicting the outcome of Crizotinib. TP53 concurrent mutation might reduce responsiveness to Crizotinib and worsen prognosis in ALK-rearranged NSCLC. CONCLUSION FISH present a certain false-negative rate although considered the gold standard. Ventana-D5F3 IHC is qualified as a screening tool, while NGS positive may predict clinical benefit of Crizotinib more accurately, allowing efficient test for specific variants and concurrent genomic alterations.

更新日期：2019-03-20

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