ALK FISH assay guides clinical decision to initiate therapy with ALK inhibitors in patients with stage IV non-small cells lung cancer (NSCLC). In this single institution retrospective study, we investigated the association between the strength of ALK positivity and progression-free survival (PFS) We screened 4,829 patients tested for ALK rearrangement by FISH from 01/06/2012 to 06/30/2018 and included 66 stage IV NSCLC ALK positive patients, who were ALK inhibitor naïve, received an ALK inhibitor, and been followed at least 10 months to the study. The median PFS for cases high positive cases [≥=50% positive nuclei; n = 49] and low positive cases [16–49% positive nuclei; n = 17] is 16 months and 4 months respectively, and the hazard ratio is 2.89 [95 CI 1.34–6.2] (p = 0.0068). When cases are stratified according to cut-off ≥=30% positive nuclei, the median PFS for cases above (n = 55) and below the cut-off (n = 11) is 12 and 3 months, respectively and the hazard ratio is 9.60 [95 CI 2.63–35.04] (p < 0.0001) Patients with low FISH positive results have shorter PFS. Although a biological reason is plausible, false positivity may be a contributing factor. For low positive results, confirmation of the FISH result with an orthogonal technology is warranted.

ALK FISH分析可指导IV期非小细胞肺癌（NSCLC）患者开始用ALK抑制剂治疗的临床决策。在这项单一机构的回顾性研究中，我们调查了ALK阳性强度与无进展生存期（PFS）之间的关联。我们从2012年6月1日至2018年6月30日筛选了4,829例通过FISH检测ALK重排的患者，其中包括66初次使用ALK抑制剂的IV期NSCLC ALK阳性患者接受了ALK抑制剂，并至少随访了10个月。高阳性病例[≥= 50％阳性核；n  = 49]和低阳性病例[16–49％阳性核；n  = 17]分别为16个月和4个月，危险比为2.89 [95 CI 1.34–6.2]（p = 0.0068）。根据截止≥30％阳性核对病例进行分层时，高于（n  = 55）和低于截止（n  = 11）的病例的中位PFS分别为12个月和3个月，危险比为9.60 [95 CI 2.63–35.04]（p  <0.0001）FISH阳性结果低的患者的PFS较短。尽管生物学原因是合理的，但假阳性可能是一个促成因素。对于低阳性结果，必须使用正交技术确认FISH结果。