Overbeck Tobias Raphael, Reiffert Annika, Schmitz Katja, Rittmeyer Achim, Körber Wolfgang, Hugo Sara, Schnalke Juliane, Lukat Laura, Hugo Tabea, Hinterthaner Marc, Reuter-Jessen Kirsten, Schildhaus Hans-Ulrich
Department of Hematology and Medical Oncology, University Medical Center Göttingen, 37075 Göttingen, Germany.
Göttingen Comprehensive Cancer Center (G-CCC), Lungentumorzentrum Universität Göttingen, 37075 Göttingen, Germany.
Cancers (Basel). 2023 May 29;15(11):2966. doi: 10.3390/cancers15112966.
(1) Background: The main objectives of our study are (i) to determine the prevalence of () fusions in a routine diagnostic setting in NSCLC (non-small cell lung cancer) and (ii) to investigate the feasibility of screening approaches including immunohistochemistry (IHC) as a first-line test accompanied by fluorescence in situ hybridization (FISH) and RNA-(ribonucleic acid-)based next-generation sequencing (RNA-NGS). (2) Methods: A total of 1068 unselected consecutive patients with NSCLC were screened in two scenarios, either with initial IHC followed by RNA-NGS ( = 973) or direct FISH testing ( = 95). (3) Results: One hundred and thirty-three patients (14.8%) were IHC positive; consecutive RNA-NGS testing revealed two patients (0.2%) with fusions ( () and ()). Positive RNA-NGS was confirmed by FISH, and -positive patients benefited from targeted treatment. All patients with direct FISH testing were negative. RNA-NGS- or FISH-positive results were mutually exclusive with alterations in (), (), (), (), () or (). Excluding patients with one of these alterations raised the prevalence of -fusion positivity among panTrk-(tropomyosin receptor kinase-) IHC positive samples to 30.5%. (4) Conclusions: fusion-positive lung cancers are exceedingly rare and account for less than 1% of patients in unselected all-comer populations. Both RNA-NGS and FISH are suitable to determine clinically relevant fusions in a real-world setting. We suggest including panTrk-IHC in a diagnostic workflow followed by RNA-NGS. Excluding patients with concurrent molecular alterations to or might narrow the target population.
(1) 背景：我们研究的主要目标是：(i) 确定在非小细胞肺癌（NSCLC）常规诊断环境中（）融合的患病率；(ii) 研究筛查方法的可行性，包括以免疫组织化学（IHC）作为一线检测方法，并辅以荧光原位杂交（FISH）和基于RNA（核糖核酸）的下一代测序（RNA-NGS）。(2) 方法：在两种情况下对总共1068例未经选择的连续NSCLC患者进行了筛查，一种是先进行IHC，然后进行RNA-NGS（n = 973），另一种是直接进行FISH检测（n = 95）。(3) 结果：133例患者（14.8%）IHC呈阳性；后续的RNA-NGS检测发现2例患者（0.2%）存在（）融合（（）和（））。FISH证实了RNA-NGS阳性，且 - 阳性患者从靶向治疗中获益。所有直接进行FISH检测的患者均为阴性。RNA-NGS或FISH阳性结果与（）、（）、（）、（）、（）或（）的改变相互排斥。排除有这些改变之一的患者后，panTrk（原肌球蛋白受体激酶）- IHC阳性样本中 - 融合阳性的患病率提高到30.5%。(4) 结论：融合阳性的肺癌极为罕见，在未经选择的所有患者群体中占比不到1%。RNA-NGS和FISH都适用于在实际临床环境中确定具有临床相关性的融合。我们建议在诊断流程中纳入panTrk-IHC，随后进行RNA-NGS。排除同时存在或分子改变的患者可能会缩小目标人群范围。
