{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:22:30Z","timestamp":1789683750618,"version":"4.0.1"},"reference-count":42,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T00:00:00Z","timestamp":1718323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"French government","award":["ANR-23-IAHU-007"],"award-info":[{"award-number":["ANR-23-IAHU-007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The identification of ALK fusions 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 through ALK FISH and\/or next-generation sequencing (NGS). Challenges arise due to the infrequency of ALK fusions (3\u20137% of aNSCLC), the suboptimal specificity of ALK IHC and ALK FISH, 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 identifying ALK fusions 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, ALK FISH, and ALK NGS. ALK IHC identified 51 positive cases (4%), while RNA NGS detected ALK alterations in 59 cases (4.8%). Of the 59 ALK-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 and ALK FISH 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 of ALK status.<\/jats:p>","DOI":"10.3390\/cancers16122219","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T03:52:53Z","timestamp":1718337173000},"page":"2219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Shifting from Immunohistochemistry to Screen for ALK Rearrangements: Real-World Experience in a Large Single-Center Cohort of Patients with Non-Small-Cell Lung Cancer"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2014-1236","authenticated-orcid":false,"given":"Marius","family":"Ili\u00e9","sequence":"first","affiliation":[{"name":"Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"},{"name":"Hospital-Integrated Biobank (BB-0033-00025), Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7082-5636","authenticated-orcid":false,"given":"Samantha","family":"Goffinet","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"},{"name":"Hospital-Integrated Biobank (BB-0033-00025), Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guyl\u00e8ne","family":"Rignol","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"},{"name":"Hospital-Integrated Biobank (BB-0033-00025), Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Lespinet-Fabre","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salom\u00e9","family":"Lalv\u00e9e","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Bordone","sequence":"additional","affiliation":[{"name":"Hospital-Integrated Biobank (BB-0033-00025), Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Zahaf","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4510-301X","authenticated-orcid":false,"given":"Christelle","family":"Bonnetaud","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"},{"name":"Hospital-Integrated Biobank (BB-0033-00025), Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Washetine","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"},{"name":"Hospital-Integrated Biobank (BB-0033-00025), Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1692-2440","authenticated-orcid":false,"given":"Sandra","family":"Lassalle","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"},{"name":"Hospital-Integrated Biobank (BB-0033-00025), Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1923-6713","authenticated-orcid":false,"given":"Elodie","family":"Long-Mira","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"},{"name":"Hospital-Integrated Biobank (BB-0033-00025), Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5916-534X","authenticated-orcid":false,"given":"Simon","family":"Heeke","sequence":"additional","affiliation":[{"name":"Department of Thoracic\/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0943-1627","authenticated-orcid":false,"given":"V\u00e9ronique","family":"Hofman","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"},{"name":"Hospital-Integrated Biobank (BB-0033-00025), Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0431-9353","authenticated-orcid":false,"given":"Paul","family":"Hofman","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"},{"name":"Hospital-Integrated Biobank (BB-0033-00025), Pasteur Hospital, Nice University Hospital, FHU OncoAge, IHU RespirERA, 06000 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1056\/NEJMoa1408440","article-title":"First-line crizotinib versus chemotherapy in ALK-positive lung cancer","volume":"371","author":"Solomon","year":"2014","journal-title":"N. 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