{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T18:44:25Z","timestamp":1770835465286,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cIntegrative strategy in development of personalized medicine of specified malignant tumours and its effect on quality of life\u201c","award":["ITMS 313011V446"],"award-info":[{"award-number":["ITMS 313011V446"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>ALK detection was performed on 2813 EGFR-unmutated NSCLC cases by simultaneous use of immunohistochemistry (VENTANA\u00ae anti-ALK D5F3, Roche Molecular Systems, Inc., Rotkreuz, Switzerland) and fluorescence in situ hybridization with the ALK break apart and the ALK\/EML4 fusion probe (ZytoVision, Bremerhaven, Germany). A total of 33 cases were positive discordant (FISH-positive, IHC-negative) and 17 cases were negative discordant (FISH-negative, IHC-positive). This study\u2019s aim was to reevaluate the methods used and compare discordant samples to positive concordant samples in order to ellucidate the differences. FISH signal variants were examined and compared. Positive discordant cases featured one pattern of ALK rearrangement in 41.4%, two patterns in 48.3%, and three patterns in 10.3% of analysed samples, with a higher variability of detected patterns and a higher number of ALK copy gains. Positive concordant cases displayed one pattern of rearrangement in 82%, two patterns in 17.8%, and three patterns in 0.6% of analysed samples. The association between number of patterns and concordance\/discordance was statistically significant (p &lt; 0.05). Eleven positive discordant and two negative concordant cases underwent NGS analysis, which resulted in identification of ALK fusion in one positive discordant and two negative discordant cases. Positive protein expression regardless of FISH result correlated more with a positive NGS result compared to samples with a positive FISH result with negative protein expression. FISH analysis was able to detect atypical or heterogenous patterns of rearrangement in a proportion of cases with negative protein expression, which may be associated with more extensive genetic alterations rather than true ALK rearrangement.<\/jats:p>","DOI":"10.3390\/ijms25158168","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T14:39:08Z","timestamp":1722004748000},"page":"8168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Discordant ALK Status in Non-Small Cell Lung Carcinoma: A Detailed Reevaluation Comparing IHC, FISH, and NGS Analyses"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9060-5348","authenticated-orcid":false,"given":"Katar\u00edna","family":"Tobi\u00e1\u0161ov\u00e1","sequence":"first","affiliation":[{"name":"Department of Pathological Anatomy, University Hospital Martin, Jessenius Faculty of Medicine, Comenius University, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Barthov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy, University Hospital Martin, Jessenius Faculty of Medicine, Comenius University, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u013duboslava","family":"Jan\u00e1kov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy, University Hospital Martin, Jessenius Faculty of Medicine, Comenius University, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katar\u00edna","family":"Le\u0161kov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy, University Hospital Martin, Jessenius Faculty of Medicine, Comenius University, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Farka\u0161ov\u00e1","sequence":"additional","affiliation":[{"name":"Martin\u2019s Biopsy Center, Ltd., 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5421-9831","authenticated-orcid":false,"given":"Du\u0161an","family":"Loderer","sequence":"additional","affiliation":[{"name":"Biomedical Centre Martin\u2014BioMed Martin, Jessenius Faculty of Medicine, Comenius University, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari\u00e1n","family":"Grend\u00e1r","sequence":"additional","affiliation":[{"name":"Biomedical Centre Martin\u2014BioMed Martin, Jessenius Faculty of Medicine, Comenius University, 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1153-1160","authenticated-orcid":false,"given":"Luk\u00e1\u0161","family":"Plank","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy, University Hospital Martin, Jessenius Faculty of Medicine, Comenius University, 036 01 Martin, Slovakia"},{"name":"Martin\u2019s Biopsy Center, Ltd., 036 01 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.annonc.2022.12.009","article-title":"Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"34","author":"Hendriks","year":"2023","journal-title":"Ann. 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