The identification ofALKfusions in advanced non-small-cell lung carcinoma (aNSCLC) is mandatory for targeted therapy. The current diagnostic approach employs an algorithm using ALK immunohistochemistry (IHC) screening, followed by confirmation throughALKFISH and/or next-generation sequencing (NGS). Challenges arise due to the infrequency ofALKfusions (3–7% of aNSCLC), the suboptimal specificity of ALK IHC andALKFISH, and the growing molecular demands placed on small tissue samples, leading to interpretative, tissue availability, and time-related issues. This study investigates the effectiveness of RNA NGS as a reflex test for identifyingALKfusions in NSCLC, with the goal of replacing ALK IHC in the systematic screening process. The evaluation included 1246 NSCLC cases using paired techniques: ALK IHC,ALKFISH, andALKNGS. ALK IHC identified 51 positive cases (4%), while RNA NGS detectedALKalterations in 59 cases (4.8%). Of the 59ALK-positive cases identified via NGS, 53 (89.8%) were confirmed to be positive. This included 51 cases detected via both FISH and IHC, and 2 cases detected only via FISH, as they were completely negative according to IHC. The combined reporting time for ALK IHC andALKFISH averaged 13 days, whereas ALK IHC and RNA NGS reports were obtained in an average of 4 days. These results emphasize the advantage of replacing systematic ALK IHC screening with RNA NGS reflex testing for a more comprehensive and accurate assessment ofALKstatus.
晚期非小细胞肺癌（aNSCLC）中ALK融合基因的检测是实施靶向治疗的必要前提。当前诊断流程采用算法化策略：先通过ALK免疫组化（IHC）初筛，再经ALK荧光原位杂交（FISH）和/或二代测序（NGS）验证。由于ALK融合发生率较低（占aNSCLC的3-7%）、ALK IHC与ALK FISH特异性不足，加之小组织样本面临的分子检测需求日益增长，导致诊断过程中存在结果判读、组织可用性及时间效率等多重挑战。本研究探讨RNA NGS作为反射性检测在NSCLC中识别ALK融合的有效性，旨在替代系统筛查流程中的ALK IHC。通过对1246例NSCLC病例进行配对技术（ALK IHC、ALK FISH和ALK NGS）评估，结果显示：ALK IHC检出阳性51例（4%），而RNA NGS检出ALK变异59例（4.8%）。在NGS检出的59例ALK阳性病例中，53例（89.8%）获得验证确认，其中51例经FISH和IHC共同检出，另有2例仅FISH阳性（IHC完全阴性）。ALK IHC与ALK FISH联合报告时间平均需13天，而ALK IHC与RNA NGS联合报告仅需平均4天。这些结果凸显了采用RNA NGS反射性检测替代系统性ALK IHC筛查，能更全面、精准地评估ALK状态的优势。
肿瘤(癌症)患者之家