Applicability of pan-TRK immunohistochemistry for identification of NTRK fusions in lung carcinoma

Abstract In the last two decades, various therapies have been introduced for lung carcinoma patients, including tyrosine-kinase inhibitors for different mutations. While some of them are specific to specific tumor types, others, like NTRK1–3 fusions, are found in various solid tumors. The occurrence...

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Autores principales:	Simon Strohmeier, Iva Brcic, Helmut Popper, Bernadette Liegl-Atzwanger, Jörg Lindenmann, Luka Brcic
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a1931cd4b02e42c9bec476b343ff09ed
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spelling	oai:doaj.org-article:a1931cd4b02e42c9bec476b343ff09ed2021-12-02T15:38:11ZApplicability of pan-TRK immunohistochemistry for identification of NTRK fusions in lung carcinoma10.1038/s41598-021-89373-32045-2322https://doaj.org/article/a1931cd4b02e42c9bec476b343ff09ed2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89373-3https://doaj.org/toc/2045-2322Abstract In the last two decades, various therapies have been introduced for lung carcinoma patients, including tyrosine-kinase inhibitors for different mutations. While some of them are specific to specific tumor types, others, like NTRK1–3 fusions, are found in various solid tumors. The occurrence of an NTRK1,2 or 3 fusion acts as a biomarker for efficient treatment with NTRK inhibitors, irrespectively of the tumor type. However, the occurrence of the NTRK1–3 fusions in lung carcinomas is extremely rare. We performed a retrospective analysis to evaluate the applicability of immunohistochemistry with the pan-TRK antibody in the detection of NTRK fusions in lung carcinomas. The study cohort included 176 adenocarcinomas (AC), 161 squamous cell carcinomas (SCC), 31 large-cell neuroendocrine carcinomas (LCNEC), and 19 small cell lung carcinomas (SCLC). Immunohistochemistry (IHC) was performed using the pan-TRK antibody (clone EPR17341, Ventana) on tissue microarrays, while confirmation for all positive cases was done using RNA-based Archer FusionPlex MUG Lung Panel. On IHC staining, 12/387 samples (3.1%) demonstrated a positive reaction. Ten SCC cases (10/161, 6.2%), and two LCNEC cases (2/31, 6.5%) were positive. Positive cases demonstrated heterogeneous staining of tumor cells, mostly membranous with some cytoplasmic and in one case nuclear pattern. RNA-based sequencing did not demonstrate any NTRK1–3 fusion in our patients’ collective. Our study demonstrates that pan-TRK expression in lung carcinoma is very low across different histologic types. NTRK1–3 fusions using an RNA-based sequencing approached could not be detected. This stresses the importance of confirmation of immunohistochemistry results by molecular methods.Simon StrohmeierIva BrcicHelmut PopperBernadette Liegl-AtzwangerJörg LindenmannLuka BrcicNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Simon Strohmeier Iva Brcic Helmut Popper Bernadette Liegl-Atzwanger Jörg Lindenmann Luka Brcic Applicability of pan-TRK immunohistochemistry for identification of NTRK fusions in lung carcinoma
description	Abstract In the last two decades, various therapies have been introduced for lung carcinoma patients, including tyrosine-kinase inhibitors for different mutations. While some of them are specific to specific tumor types, others, like NTRK1–3 fusions, are found in various solid tumors. The occurrence of an NTRK1,2 or 3 fusion acts as a biomarker for efficient treatment with NTRK inhibitors, irrespectively of the tumor type. However, the occurrence of the NTRK1–3 fusions in lung carcinomas is extremely rare. We performed a retrospective analysis to evaluate the applicability of immunohistochemistry with the pan-TRK antibody in the detection of NTRK fusions in lung carcinomas. The study cohort included 176 adenocarcinomas (AC), 161 squamous cell carcinomas (SCC), 31 large-cell neuroendocrine carcinomas (LCNEC), and 19 small cell lung carcinomas (SCLC). Immunohistochemistry (IHC) was performed using the pan-TRK antibody (clone EPR17341, Ventana) on tissue microarrays, while confirmation for all positive cases was done using RNA-based Archer FusionPlex MUG Lung Panel. On IHC staining, 12/387 samples (3.1%) demonstrated a positive reaction. Ten SCC cases (10/161, 6.2%), and two LCNEC cases (2/31, 6.5%) were positive. Positive cases demonstrated heterogeneous staining of tumor cells, mostly membranous with some cytoplasmic and in one case nuclear pattern. RNA-based sequencing did not demonstrate any NTRK1–3 fusion in our patients’ collective. Our study demonstrates that pan-TRK expression in lung carcinoma is very low across different histologic types. NTRK1–3 fusions using an RNA-based sequencing approached could not be detected. This stresses the importance of confirmation of immunohistochemistry results by molecular methods.
format	article
author	Simon Strohmeier Iva Brcic Helmut Popper Bernadette Liegl-Atzwanger Jörg Lindenmann Luka Brcic
author_facet	Simon Strohmeier Iva Brcic Helmut Popper Bernadette Liegl-Atzwanger Jörg Lindenmann Luka Brcic
author_sort	Simon Strohmeier
title	Applicability of pan-TRK immunohistochemistry for identification of NTRK fusions in lung carcinoma
title_short	Applicability of pan-TRK immunohistochemistry for identification of NTRK fusions in lung carcinoma
title_full	Applicability of pan-TRK immunohistochemistry for identification of NTRK fusions in lung carcinoma
title_fullStr	Applicability of pan-TRK immunohistochemistry for identification of NTRK fusions in lung carcinoma
title_full_unstemmed	Applicability of pan-TRK immunohistochemistry for identification of NTRK fusions in lung carcinoma
title_sort	applicability of pan-trk immunohistochemistry for identification of ntrk fusions in lung carcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a1931cd4b02e42c9bec476b343ff09ed
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Applicability of pan-TRK immunohistochemistry for identification of NTRK fusions in lung carcinoma

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