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EGFR mutation status in Tunisian non-small-cell lung cancer patients evaluated by mutation-specific immunohistochemistry
BACKGROUND: Screening mutations in epidermal growth factor receptor (EGFR) to analyze non-small-cell lung cancer (NSCLC) profile is the criterion to choose the best therapeutic strategy. New Oncology guidelines recommend EGFR mutation analysis before prescribing tyrosine kinase inhibitors (TKIs) tre...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085720/ https://www.ncbi.nlm.nih.gov/pubmed/30092812 http://dx.doi.org/10.1186/s12890-018-0706-5 |
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author | Mraihi, Zohra Ben Amar, Jihen Bouacha, Hend Rammeh, Soumaya Hila, Lamia |
author_facet | Mraihi, Zohra Ben Amar, Jihen Bouacha, Hend Rammeh, Soumaya Hila, Lamia |
author_sort | Mraihi, Zohra |
collection | PubMed |
description | BACKGROUND: Screening mutations in epidermal growth factor receptor (EGFR) to analyze non-small-cell lung cancer (NSCLC) profile is the criterion to choose the best therapeutic strategy. New Oncology guidelines recommend EGFR mutation analysis before prescribing tyrosine kinase inhibitors (TKIs) treatment. Majority of lung cancer patients are diagnosed at advanced stages and generally only small biopsies materials are available for diagnostic and molecular characterization. The aim of this first work is to screen EGFR mutation status in Tunisian NSCLC by mutation-specific immunohistochemistry (IHC) and molecular biology, to estimate the relevance of proposing TKIs as a new therapeutic line. METHODS: E746-A750 deletion and L858R mutations were screened in 50 unselected NSCLC formalin-fixed paraffin-embedded (FFPE) tissue samples. Mutation expression by IHC was evaluated by intensity and percentage of staining and correlated to patients’ data. DNA was extracted and EGFR mutations were analyzed by Sanger sequencing. Positive and negative controls were included for EGFR mutations in order to support the results. RESULTS: Among our patients (48 men and 2 women) all adenocarcinoma (confirmed by histology and IHC with TTF1/Napsin A), 94% were smokers exceeding the tobacco risk threshold (at least 25 pack-years) and the women were none. 44% had EGFR mutation by IHC: 26% had simple mutation and 18% had concurrent mutation. All mutated cases were smokers except a woman who was none. Concurrent mutations patients exceeded 40 pack-years. 91.4% of IHC results were validated by molecular analysis (100% of negative and 85% of positive cases) showing either T > G (exon 21) or 2235–2249 del (exon 19). CONCLUSIONS: These preliminary results confirm the usefulness of IHC to detect EGFR mutations but the frequency of concurrent mutations doesn’t appear in favor of EGFR TKIs treatment. In fact, literature reports a significantly worse response compared to those with single mutation when treated by TKIs. |
format | Online Article Text |
id | pubmed-6085720 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60857202018-08-16 EGFR mutation status in Tunisian non-small-cell lung cancer patients evaluated by mutation-specific immunohistochemistry Mraihi, Zohra Ben Amar, Jihen Bouacha, Hend Rammeh, Soumaya Hila, Lamia BMC Pulm Med Research Article BACKGROUND: Screening mutations in epidermal growth factor receptor (EGFR) to analyze non-small-cell lung cancer (NSCLC) profile is the criterion to choose the best therapeutic strategy. New Oncology guidelines recommend EGFR mutation analysis before prescribing tyrosine kinase inhibitors (TKIs) treatment. Majority of lung cancer patients are diagnosed at advanced stages and generally only small biopsies materials are available for diagnostic and molecular characterization. The aim of this first work is to screen EGFR mutation status in Tunisian NSCLC by mutation-specific immunohistochemistry (IHC) and molecular biology, to estimate the relevance of proposing TKIs as a new therapeutic line. METHODS: E746-A750 deletion and L858R mutations were screened in 50 unselected NSCLC formalin-fixed paraffin-embedded (FFPE) tissue samples. Mutation expression by IHC was evaluated by intensity and percentage of staining and correlated to patients’ data. DNA was extracted and EGFR mutations were analyzed by Sanger sequencing. Positive and negative controls were included for EGFR mutations in order to support the results. RESULTS: Among our patients (48 men and 2 women) all adenocarcinoma (confirmed by histology and IHC with TTF1/Napsin A), 94% were smokers exceeding the tobacco risk threshold (at least 25 pack-years) and the women were none. 44% had EGFR mutation by IHC: 26% had simple mutation and 18% had concurrent mutation. All mutated cases were smokers except a woman who was none. Concurrent mutations patients exceeded 40 pack-years. 91.4% of IHC results were validated by molecular analysis (100% of negative and 85% of positive cases) showing either T > G (exon 21) or 2235–2249 del (exon 19). CONCLUSIONS: These preliminary results confirm the usefulness of IHC to detect EGFR mutations but the frequency of concurrent mutations doesn’t appear in favor of EGFR TKIs treatment. In fact, literature reports a significantly worse response compared to those with single mutation when treated by TKIs. BioMed Central 2018-08-09 /pmc/articles/PMC6085720/ /pubmed/30092812 http://dx.doi.org/10.1186/s12890-018-0706-5 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Mraihi, Zohra Ben Amar, Jihen Bouacha, Hend Rammeh, Soumaya Hila, Lamia EGFR mutation status in Tunisian non-small-cell lung cancer patients evaluated by mutation-specific immunohistochemistry |
title | EGFR mutation status in Tunisian non-small-cell lung cancer patients evaluated by mutation-specific immunohistochemistry |
title_full | EGFR mutation status in Tunisian non-small-cell lung cancer patients evaluated by mutation-specific immunohistochemistry |
title_fullStr | EGFR mutation status in Tunisian non-small-cell lung cancer patients evaluated by mutation-specific immunohistochemistry |
title_full_unstemmed | EGFR mutation status in Tunisian non-small-cell lung cancer patients evaluated by mutation-specific immunohistochemistry |
title_short | EGFR mutation status in Tunisian non-small-cell lung cancer patients evaluated by mutation-specific immunohistochemistry |
title_sort | egfr mutation status in tunisian non-small-cell lung cancer patients evaluated by mutation-specific immunohistochemistry |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085720/ https://www.ncbi.nlm.nih.gov/pubmed/30092812 http://dx.doi.org/10.1186/s12890-018-0706-5 |
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