{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:00:44Z","timestamp":1790629244927,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T00:00:00Z","timestamp":1600128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Recently, a novel isoform of anaplastic lymphoma kinase, with alternative transcription initiation (ALK<jats:sup>ATI<\/jats:sup>), has been described in melanoma and is susceptible to targeted ALK\u2010inhibitor therapy. Clinical outcomes of patients with ALK<jats:sup>ATI<\/jats:sup> mutated melanoma as well as correlation with immunohistochemical (IHC) methods have not yet been described.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Clinicopathological characteristics were abstracted for 324 patients with metastatic melanoma (MM). IHC, fluorescence <jats:italic>in\u2010situ<\/jats:italic> hybridisation and RNA\u2010based digital molecular analysis assays were performed on archival tissue from 173 stage III and 192 stage IV tumours. ALK<jats:sup>ATI<\/jats:sup> was identified in 12.7 and 4.8% stage III and IV tumours, respectively. Discrete presentations of the ALK<jats:sup>ATI<\/jats:sup> are seen: isolated ALK<jats:sup>ATI<\/jats:sup> (<jats:italic>n<\/jats:italic>\u00a0=\u00a020) and mixed ALK<jats:sup>ATI<\/jats:sup> (combined ALK<jats:sup>ATI<\/jats:sup> and ALK<jats:sup>WT<\/jats:sup>; <jats:italic>n<\/jats:italic>\u00a0=\u00a07). Isolated ALK<jats:sup>WT<\/jats:sup> expression (<jats:italic>n<\/jats:italic>\u00a0=\u00a04) was seen with no ALK fusions. Stage III patients showed improved survival with ALK<jats:sup>ATI<\/jats:sup> expression compared to those with ALK<jats:sup>WT<\/jats:sup> or no expression [5\u2010year survival 80, 95% confidence interval (CI)\u00a0=\u00a057\u2013100% versus 43%, 95% CI\u00a0=\u00a034\u201355%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.013]. Clinicopathological characteristics were not statistically significant. Strong diffuse cytoplasmic staining of ALK IHC (<jats:italic>n<\/jats:italic>\u00a0=\u00a012) has a sensitivity of 52.2%, specificity 100%, PPV of 100% and NPV of 92.5% of detecting isolated ALK<jats:sup>ATI<\/jats:sup>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Presence of ALK<jats:sup>ATI<\/jats:sup> is a good prognostic indicator in MM. ALK IHC and digital molecular analysis can be incorporated into MM evaluation to identify patients with ALK<jats:sup>ATI<\/jats:sup> for targeted therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14191","type":"journal-article","created":{"date-parts":[[2020,6,21]],"date-time":"2020-06-21T08:29:21Z","timestamp":1592728161000},"page":"601-610","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Correlation of novel ALK<sup>ATI<\/sup> with ALK immunohistochemistry and clinical outcomes in metastatic melanoma"],"prefix":"10.1111","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7767-0278","authenticated-orcid":false,"given":"Kabeer K","family":"Shah","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA"},{"name":"Division of Dermatopathology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jadee L","family":"Neff","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA"},{"name":"Division of Laboratory Genetics Mayo Clinic Rochester MN USA"},{"name":"Department of Pathology Duke University School of Medicine Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3666-2546","authenticated-orcid":false,"given":"Lori A","family":"Erickson","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA"},{"name":"Division of Dermatopathology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory A","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA"},{"name":"Division of Laboratory Genetics Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Division of Biomedical Statistics and Informatics Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron S","family":"Mansfield","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Mayo Clinic Rochester MN USA"},{"name":"Department of Medicine Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin C","family":"Moser","sequence":"additional","affiliation":[{"name":"Department of Medicine Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoneicka L","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology Mayo Clinic Florida Jacksonville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A","family":"Copland","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology Mayo Clinic Florida Jacksonville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin C","family":"Halling","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA"},{"name":"Division of Laboratory Genetics Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J","family":"Flotte","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA"},{"name":"Division of Dermatopathology Mayo Clinic Rochester MN 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