NTRK gene aberrations in triple‐negative breast cancer: detection challenges using IHC, FISH, RT‐PCR, and NGS
Abstract Triple‐negative 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‐agnostic emerging biomarkers approved by the Food and Drug Administration (FDA), USA, for...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-09-01
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| Series: | The Journal of Pathology: Clinical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cjp2.324 |
| _version_ | 1827878447837347840 |
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| author | Federica Zito Marino Simona Buono Marco Montella Rosa Giannatiempo Francesco Messina Giovanni Casaretta Grazia Arpino Giulia Vita Francesco Fiorentino Luigi Insabato Alessandro Sgambato Michele Orditura Renato Franco Marina Accardo |
| author_facet | Federica Zito Marino Simona Buono Marco Montella Rosa Giannatiempo Francesco Messina Giovanni Casaretta Grazia Arpino Giulia Vita Francesco Fiorentino Luigi Insabato Alessandro Sgambato Michele Orditura Renato Franco Marina Accardo |
| author_sort | Federica Zito Marino |
| collection | DOAJ |
| description | Abstract Triple‐negative 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‐agnostic 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 NTRK 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‐TRK immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), real‐time polymerase chain reaction (RT‐PCR), and RNA‐based next‐generation sequencing (NGS). Of 83 cases, 16 showed pan‐TRK positivity although no cases had NTRK‐fusions. Indeed, FISH showed four cases carrying an atypical NTRK1 pattern consisting of one fusion signal and one/more single green signals, but all cases were negative for fusion by NGS and RT‐PCR testing. In addition, FISH analysis showed six cases with NTRK1 amplification, one case with NTRK2 copy number gain, and five cases with NTRK3 copy number gain, all negative for pan‐TRK IHC. Our data demonstrate that IHC has a high false‐positive 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 NTRK 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. |
| first_indexed | 2024-03-12T17:52:42Z |
| format | Article |
| id | doaj.art-92e0f09f3c1947ca80404c43828e4f6a |
| institution | Directory Open Access Journal |
| issn | 2056-4538 |
| language | English |
| last_indexed | 2024-03-12T17:52:42Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Journal of Pathology: Clinical Research |
| spelling | doaj.art-92e0f09f3c1947ca80404c43828e4f6a2023-08-03T03:59:59ZengWileyThe Journal of Pathology: Clinical Research2056-45382023-09-019536737710.1002/cjp2.324NTRK gene aberrations in triple‐negative breast cancer: detection challenges using IHC, FISH, RT‐PCR, and NGSFederica Zito Marino0Simona Buono1Marco Montella2Rosa Giannatiempo3Francesco Messina4Giovanni Casaretta5Grazia Arpino6Giulia Vita7Francesco Fiorentino8Luigi Insabato9Alessandro Sgambato10Michele Orditura11Renato Franco12Marina Accardo13Pathology Unit, Department of Mental and Physical Health and Preventive Medicine University of Campania “L. Vanvitelli” Naples ItalyPathology Unit, Department of Mental and Physical Health and Preventive Medicine University of Campania “L. Vanvitelli” Naples ItalyPathology Unit, Department of Mental and Physical Health and Preventive Medicine University of Campania “L. Vanvitelli” Naples ItalyOspedale Evangelico Betania Naples ItalyOspedale Evangelico Betania Naples ItalyOspedale Evangelico Betania Naples ItalyDepartment of Clinical Medicine and Surgery University of Naples Federico II Naples ItalyAnatomical Pathology Department, IRCCS CROB Rionero in Vulture ItalyPathology Unit S.M. delle Grazie Hospital Naples ItalyDepartment of Advanced Biomedical Sciences, Pathology Section University of Naples “Federico II” Naples ItalyScientific Direction, Centro di Riferimento Oncologico della Basilicata (IRCCS‐CROB) Rionero in Vulture ItalyDivision of Medical Oncology, Department of Precision Medicine, School of Medicine University of Campania “L. Vanvitelli” Naples ItalyPathology Unit, Department of Mental and Physical Health and Preventive Medicine University of Campania “L. Vanvitelli” Naples ItalyPathology Unit, Department of Mental and Physical Health and Preventive Medicine University of Campania “L. Vanvitelli” Naples ItalyAbstract Triple‐negative 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‐agnostic 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 NTRK 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‐TRK immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), real‐time polymerase chain reaction (RT‐PCR), and RNA‐based next‐generation sequencing (NGS). Of 83 cases, 16 showed pan‐TRK positivity although no cases had NTRK‐fusions. Indeed, FISH showed four cases carrying an atypical NTRK1 pattern consisting of one fusion signal and one/more single green signals, but all cases were negative for fusion by NGS and RT‐PCR testing. In addition, FISH analysis showed six cases with NTRK1 amplification, one case with NTRK2 copy number gain, and five cases with NTRK3 copy number gain, all negative for pan‐TRK IHC. Our data demonstrate that IHC has a high false‐positive 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 NTRK 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.https://doi.org/10.1002/cjp2.324triple‐negative breast carcinomaneurotrophic tyrosine receptor kinase (NTRK)NTRK fusionsNTRK amplificationIHCFISH |
| spellingShingle | Federica Zito Marino Simona Buono Marco Montella Rosa Giannatiempo Francesco Messina Giovanni Casaretta Grazia Arpino Giulia Vita Francesco Fiorentino Luigi Insabato Alessandro Sgambato Michele Orditura Renato Franco Marina Accardo NTRK gene aberrations in triple‐negative breast cancer: detection challenges using IHC, FISH, RT‐PCR, and NGS The Journal of Pathology: Clinical Research triple‐negative breast carcinoma neurotrophic tyrosine receptor kinase (NTRK) NTRK fusions NTRK amplification IHC FISH |
| title | NTRK gene aberrations in triple‐negative breast cancer: detection challenges using IHC, FISH, RT‐PCR, and NGS |
| title_full | NTRK gene aberrations in triple‐negative breast cancer: detection challenges using IHC, FISH, RT‐PCR, and NGS |
| title_fullStr | NTRK gene aberrations in triple‐negative breast cancer: detection challenges using IHC, FISH, RT‐PCR, and NGS |
| title_full_unstemmed | NTRK gene aberrations in triple‐negative breast cancer: detection challenges using IHC, FISH, RT‐PCR, and NGS |
| title_short | NTRK gene aberrations in triple‐negative breast cancer: detection challenges using IHC, FISH, RT‐PCR, and NGS |
| title_sort | ntrk gene aberrations in triple negative breast cancer detection challenges using ihc fish rt pcr and ngs |
| topic | triple‐negative breast carcinoma neurotrophic tyrosine receptor kinase (NTRK) NTRK fusions NTRK amplification IHC FISH |
| url | https://doi.org/10.1002/cjp2.324 |
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