Uncommon EGFR mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients

Elisna Syahruddin,1,2 Laksmi Wulandari,3 Nunuk Sri Muktiati,4 Ana Rima,5 Noni Soeroso,6 Sabrina Ermayanti,7 Michael Levi,8 Heriawaty Hidajat,2 Grace Widjajahakim,8 Ahmad Rusdan Handoyo Utomo9 1Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Indonesia; 2Department...

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Autores principales:	Syahruddin E, Wulandari L, Sri Muktiati N, Rima A, Soeroso N, Ermayanti S, Levi M, Hidajat H, Widjajahakim G, Utomo ARH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	EGFR mutations Lung cancer treatment naive T790M Tyrosine Kinase inhibitors Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/416da6b05a494d97b52271f2dbf78404
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spelling	oai:doaj.org-article:416da6b05a494d97b52271f2dbf784042021-12-02T01:54:45ZUncommon EGFR mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients1179-2728https://doaj.org/article/416da6b05a494d97b52271f2dbf784042018-03-01T00:00:00Zhttps://www.dovepress.com/uncommon-egfr-mutations-in-cytological-specimens-of-1874--newly-diagno-peer-reviewed-article-LCTThttps://doaj.org/toc/1179-2728Elisna Syahruddin,1,2 Laksmi Wulandari,3 Nunuk Sri Muktiati,4 Ana Rima,5 Noni Soeroso,6 Sabrina Ermayanti,7 Michael Levi,8 Heriawaty Hidajat,2 Grace Widjajahakim,8 Ahmad Rusdan Handoyo Utomo9 1Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Indonesia; 2Department of Pulmonology, Persahabatan Hospital, Jakarta, Indonesia; 3Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga – Soetomo Hospital, Surabaya, Indonesia; 4Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Brawijaya – Saiful Anwar General Hospital, Malang, Indonesia; 5Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Sebelas Maret, Dr. Moewardi General Hospital, Surakarta, Indonesia; 6Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, University of Sumatera Utara, Adam Malik General Hospital, Medan, Indonesia; 7Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Andalas University, M. Djamil Hospital, Padang, Indonesia; 8Kalbe Genomics Laboratory, Division of Molecular Pathology Testing Service, PT Bifarma Adiluhung, 9Stem Cell and Cancer Institute, Cancer Diagnostic Research Division, PT Kalbe Farma Tbk, Jakarta, Indonesia Purpose: We aimed to evaluate the distribution of individual epidermal growth factor receptor (EGFR) mutation subtypes found in routine cytological specimens.Patients and methods: A retrospective audit was performed on EGFR testing results of 1,874 consecutive cytological samples of newly diagnosed or treatment-naïve Indonesian lung cancer patients (years 2015–2016). Testing was performed by ISO15189 accredited central laboratory.Results: Overall test failure rate was 5.1%, with the highest failure (7.1%) observed in pleural effusion and lowest (1.6%) in needle aspiration samples. EGFR mutation frequency was 44.4%. Tyrosine kinase inhibitor (TKI)-sensitive common EGFR mutations (ins/dels exon 19, L858R) and uncommon mutations (G719X, T790M, L861Q) contributed 57.1% and 29%, respectively. Approximately 13.9% of mutation-positive patients carried a mixture of common and uncommon mutations. Women had higher EGFR mutation rate (52.9%) vs men (39.1%; p<0.05). In contrast, uncommon mutations conferring either TKI responsive (G719X, L861Q) or TKI resistance (T790M, exon 20 insertions) were consistently more frequent in men than in women (67.3% vs 32.7% or 69.4% vs 30.6%; p<0.05). Up to 10% EGFR mutation–positive patients had baseline single mutation T790M, exon 20 insertion, or in coexistence with TKI-sensitive mutations. Up to 9% patients had complex or multiple EGFR mutations, whereby 48.7% patients harbored TKI-resistant mutations. One patient presented third-generation TKI-resistant mutation L792F simultaneously with T790M.Conclusion: Routine diagnostic cytological techniques yielded similar success rate to detect EGFR mutations. Uncommon EGFR mutations were frequent events in Indonesian lung cancer patients. Keywords: EGFR mutations, lung cancer, treatment naive, T790M, tyrosine kinase inhibitor, Indonesia, cytologySyahruddin EWulandari LSri Muktiati NRima ASoeroso NErmayanti SLevi MHidajat HWidjajahakim GUtomo ARHDove Medical PressarticleEGFR mutationsLung cancertreatment naiveT790MTyrosine Kinase inhibitorsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol Volume 9, Pp 25-34 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	EGFR mutations Lung cancer treatment naive T790M Tyrosine Kinase inhibitors Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	EGFR mutations Lung cancer treatment naive T790M Tyrosine Kinase inhibitors Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Syahruddin E Wulandari L Sri Muktiati N Rima A Soeroso N Ermayanti S Levi M Hidajat H Widjajahakim G Utomo ARH Uncommon EGFR mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients
description	Elisna Syahruddin,1,2 Laksmi Wulandari,3 Nunuk Sri Muktiati,4 Ana Rima,5 Noni Soeroso,6 Sabrina Ermayanti,7 Michael Levi,8 Heriawaty Hidajat,2 Grace Widjajahakim,8 Ahmad Rusdan Handoyo Utomo9 1Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Indonesia; 2Department of Pulmonology, Persahabatan Hospital, Jakarta, Indonesia; 3Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga – Soetomo Hospital, Surabaya, Indonesia; 4Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Brawijaya – Saiful Anwar General Hospital, Malang, Indonesia; 5Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Sebelas Maret, Dr. Moewardi General Hospital, Surakarta, Indonesia; 6Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, University of Sumatera Utara, Adam Malik General Hospital, Medan, Indonesia; 7Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Andalas University, M. Djamil Hospital, Padang, Indonesia; 8Kalbe Genomics Laboratory, Division of Molecular Pathology Testing Service, PT Bifarma Adiluhung, 9Stem Cell and Cancer Institute, Cancer Diagnostic Research Division, PT Kalbe Farma Tbk, Jakarta, Indonesia Purpose: We aimed to evaluate the distribution of individual epidermal growth factor receptor (EGFR) mutation subtypes found in routine cytological specimens.Patients and methods: A retrospective audit was performed on EGFR testing results of 1,874 consecutive cytological samples of newly diagnosed or treatment-naïve Indonesian lung cancer patients (years 2015–2016). Testing was performed by ISO15189 accredited central laboratory.Results: Overall test failure rate was 5.1%, with the highest failure (7.1%) observed in pleural effusion and lowest (1.6%) in needle aspiration samples. EGFR mutation frequency was 44.4%. Tyrosine kinase inhibitor (TKI)-sensitive common EGFR mutations (ins/dels exon 19, L858R) and uncommon mutations (G719X, T790M, L861Q) contributed 57.1% and 29%, respectively. Approximately 13.9% of mutation-positive patients carried a mixture of common and uncommon mutations. Women had higher EGFR mutation rate (52.9%) vs men (39.1%; p<0.05). In contrast, uncommon mutations conferring either TKI responsive (G719X, L861Q) or TKI resistance (T790M, exon 20 insertions) were consistently more frequent in men than in women (67.3% vs 32.7% or 69.4% vs 30.6%; p<0.05). Up to 10% EGFR mutation–positive patients had baseline single mutation T790M, exon 20 insertion, or in coexistence with TKI-sensitive mutations. Up to 9% patients had complex or multiple EGFR mutations, whereby 48.7% patients harbored TKI-resistant mutations. One patient presented third-generation TKI-resistant mutation L792F simultaneously with T790M.Conclusion: Routine diagnostic cytological techniques yielded similar success rate to detect EGFR mutations. Uncommon EGFR mutations were frequent events in Indonesian lung cancer patients. Keywords: EGFR mutations, lung cancer, treatment naive, T790M, tyrosine kinase inhibitor, Indonesia, cytology
format	article
author	Syahruddin E Wulandari L Sri Muktiati N Rima A Soeroso N Ermayanti S Levi M Hidajat H Widjajahakim G Utomo ARH
author_facet	Syahruddin E Wulandari L Sri Muktiati N Rima A Soeroso N Ermayanti S Levi M Hidajat H Widjajahakim G Utomo ARH
author_sort	Syahruddin E
title	Uncommon EGFR mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients
title_short	Uncommon EGFR mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients
title_full	Uncommon EGFR mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients
title_fullStr	Uncommon EGFR mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients
title_full_unstemmed	Uncommon EGFR mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients
title_sort	uncommon egfr mutations in cytological specimens of 1,874 newly diagnosed indonesian lung cancer patients
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/416da6b05a494d97b52271f2dbf78404
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Uncommon EGFR mutations in cytological specimens of 1,874 newly diagnosed Indonesian lung cancer patients

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