{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T17:25:25Z","timestamp":1791739525846,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T00:00:00Z","timestamp":1683158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Triple\u2010negative breast cancer (TNBC) is usually an aggressive disease with a poor prognosis and limited treatment options. The neurotrophic tyrosine receptor kinase (NTRK) gene fusions are cancer type\u2010agnostic emerging biomarkers approved by the Food and Drug Administration (FDA), USA, for the selection of patients for targeted therapy. The main aim of our study was to investigate the frequency of <jats:italic>NTRK<\/jats:italic> aberrations, i.e. fusions, gene copy number gain, and amplification, in a series of TNBC using different methods. A total of 83 TNBCs were analyzed using pan\u2010TRK immunohistochemistry (IHC), fluorescence <jats:italic>in situ<\/jats:italic> hybridization (FISH), real\u2010time polymerase chain reaction (RT\u2010PCR), and RNA\u2010based next\u2010generation sequencing (NGS). Of 83 cases, 16 showed pan\u2010TRK positivity although no cases had <jats:italic>NTRK<\/jats:italic>\u2010fusions. Indeed, FISH showed four cases carrying an atypical <jats:italic>NTRK1<\/jats:italic> pattern consisting of one fusion signal and one\/more single green signals, but all cases were negative for fusion by NGS and RT\u2010PCR testing. In addition, FISH analysis showed six cases with <jats:italic>NTRK1<\/jats:italic> amplification, one case with <jats:italic>NTRK2<\/jats:italic> copy number gain, and five cases with <jats:italic>NTRK3<\/jats:italic> copy number gain, all negative for pan\u2010TRK IHC. Our data demonstrate that IHC has a high false\u2010positive rate for the detection of fusions and molecular testing is mandatory; there is no need to perform additional molecular tests in cases negativity for NTRK by IHC. In conclusion, the <jats:italic>NTRK<\/jats:italic> genes are not involved in fusions in TNBC, but both copy number gain and amplification are frequent events, suggesting a possible predictive role for other NTRK aberrations.<\/jats:p>","DOI":"10.1002\/cjp2.324","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T01:42:00Z","timestamp":1683250920000},"page":"367-377","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["<scp><i>NTRK<\/i><\/scp> gene aberrations in triple\u2010negative breast cancer: detection challenges using <scp>IHC<\/scp>, <scp>FISH<\/scp>, <scp>RT\u2010PCR,<\/scp> and <scp>NGS<\/scp>"],"prefix":"10.1002","volume":"9","author":[{"given":"Federica","family":"Zito Marino","sequence":"first","affiliation":[{"name":"Pathology Unit, Department of Mental and Physical Health and Preventive Medicine University of Campania \u201cL. Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Buono","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Mental and Physical Health and Preventive Medicine University of Campania \u201cL. Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Montella","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Mental and Physical Health and Preventive Medicine University of Campania \u201cL. Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Giannatiempo","sequence":"additional","affiliation":[{"name":"Ospedale Evangelico Betania  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Messina","sequence":"additional","affiliation":[{"name":"Ospedale Evangelico Betania  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Casaretta","sequence":"additional","affiliation":[{"name":"Ospedale Evangelico Betania  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Arpino","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Vita","sequence":"additional","affiliation":[{"name":"Anatomical Pathology Department, IRCCS CROB  Rionero in Vulture Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"Pathology Unit S.M. delle Grazie Hospital  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Insabato","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, Pathology Section University of Naples \u201cFederico II\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Sgambato","sequence":"additional","affiliation":[{"name":"Scientific Direction, Centro di Riferimento Oncologico della Basilicata (IRCCS\u2010CROB)  Rionero in Vulture Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Orditura","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Precision Medicine, School of Medicine University of Campania \u201cL. Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Franco","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Mental and Physical Health and Preventive Medicine University of Campania \u201cL. Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Accardo","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Mental and Physical Health and Preventive Medicine University of Campania \u201cL. Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000004321"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-1177"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-38364-y"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0113-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10040105"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21103718"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz204"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-019-01610-y"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0324-7"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.23838\/pfm.2017.00142"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222212332"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12030668"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0118-3"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.654387"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.6529"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21144927"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/pin.12766"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clbc.2018.09.001"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-3165"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2010-0351-RS"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-018-1044-x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13133376"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAI.0000000000000360"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2022.06.030"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2020-0400-RA"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03099-x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000487"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2019.02.015"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2017-0134-RA"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737140.2016.1162098"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2019-0641"},{"key":"e_1_2_9_33_1","unstructured":"Larotrectinib for the Treatment of NTRK Amplification Positive Locally Advanced or Metastatic Solid Tumors.\u00a0[Accessed 4 August 2022]. Available from:https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04879121"}],"container-title":["The Journal of Pathology: Clinical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cjp2.324","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T13:37:53Z","timestamp":1760276273000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cjp2.324"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,4]]},"references-count":32,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["10.1002\/cjp2.324"],"URL":"https:\/\/doi.org\/10.1002\/cjp2.324","archive":["Portico"],"relation":{},"ISSN":["2056-4538","2056-4538"],"issn-type":[{"value":"2056-4538","type":"print"},{"value":"2056-4538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,4]]},"assertion":[{"value":"2022-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}