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Validation of Immunohistochemistry for the Detection of BRAF V600E-Mutated Lung Adenocarcinomas

BRAF V600E mutation, a missense mutation in exon 15 resulting in valine substitution for glutamate at position 600 within the kinase domain of BRAF oncogene, is found in a subset of lung adenocarcinoma (ADC). The usefulness of immunohistochemistry (IHC) as an alternative diagnostic tool has not been...

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Autores principales: Gow, Chien-Hung, Hsieh, Min-Shu, Lin, Yen-Ting, Liu, Yi-Nan, Shih, Jin-Yuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627826/
https://www.ncbi.nlm.nih.gov/pubmed/31234388
http://dx.doi.org/10.3390/cancers11060866
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author Gow, Chien-Hung
Hsieh, Min-Shu
Lin, Yen-Ting
Liu, Yi-Nan
Shih, Jin-Yuan
author_facet Gow, Chien-Hung
Hsieh, Min-Shu
Lin, Yen-Ting
Liu, Yi-Nan
Shih, Jin-Yuan
author_sort Gow, Chien-Hung
collection PubMed
description BRAF V600E mutation, a missense mutation in exon 15 resulting in valine substitution for glutamate at position 600 within the kinase domain of BRAF oncogene, is found in a subset of lung adenocarcinoma (ADC). The usefulness of immunohistochemistry (IHC) as an alternative diagnostic tool has not been validated. Moreover, the clinical information of patients with BRAF V600E-mutated lung ADC is limited. We retrospectively identified 31 lung ADCs diagnosed with BRAF V600E mutation by standard molecular sequencing methods and reviewed their clinical characteristics and pathological features. An anti-BRAF V600E monoclonal VE1 antibody for IHC was used to confirm the expression patterns. The series was comprised of 99 cases, 29 with BRAF V600E mutation and 70 without BRAF V600E but with other types or undetected mutations. The majority of BRAF V600E-mutated biopsied tissues were poorly differentiated and micropapillary patterns. Application of the IHC VE1 assay was highly feasible in primary/metastatic sites or effusion blocks, yielding positive findings in 28 of 29 (96.6%) BRAF V600E-mutated tumors and negative results in 69 of 70 (98.6%) tumors harboring other types or undetected mutations. Patients who received pemetrexed/platinum-based rather than mutation-targeted chemotherapy as the first-line therapy for metastatic disease showed median overall survival of 15.5 months. Our findings indicated that VE1 antibody-based IHC analysis demonstrated high sensitivity and specificity to detect BRAF V600E-mutated lung ADCs in tissues from primary or metastatic sites.
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spelling pubmed-66278262019-07-23 Validation of Immunohistochemistry for the Detection of BRAF V600E-Mutated Lung Adenocarcinomas Gow, Chien-Hung Hsieh, Min-Shu Lin, Yen-Ting Liu, Yi-Nan Shih, Jin-Yuan Cancers (Basel) Article BRAF V600E mutation, a missense mutation in exon 15 resulting in valine substitution for glutamate at position 600 within the kinase domain of BRAF oncogene, is found in a subset of lung adenocarcinoma (ADC). The usefulness of immunohistochemistry (IHC) as an alternative diagnostic tool has not been validated. Moreover, the clinical information of patients with BRAF V600E-mutated lung ADC is limited. We retrospectively identified 31 lung ADCs diagnosed with BRAF V600E mutation by standard molecular sequencing methods and reviewed their clinical characteristics and pathological features. An anti-BRAF V600E monoclonal VE1 antibody for IHC was used to confirm the expression patterns. The series was comprised of 99 cases, 29 with BRAF V600E mutation and 70 without BRAF V600E but with other types or undetected mutations. The majority of BRAF V600E-mutated biopsied tissues were poorly differentiated and micropapillary patterns. Application of the IHC VE1 assay was highly feasible in primary/metastatic sites or effusion blocks, yielding positive findings in 28 of 29 (96.6%) BRAF V600E-mutated tumors and negative results in 69 of 70 (98.6%) tumors harboring other types or undetected mutations. Patients who received pemetrexed/platinum-based rather than mutation-targeted chemotherapy as the first-line therapy for metastatic disease showed median overall survival of 15.5 months. Our findings indicated that VE1 antibody-based IHC analysis demonstrated high sensitivity and specificity to detect BRAF V600E-mutated lung ADCs in tissues from primary or metastatic sites. MDPI 2019-06-21 /pmc/articles/PMC6627826/ /pubmed/31234388 http://dx.doi.org/10.3390/cancers11060866 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gow, Chien-Hung
Hsieh, Min-Shu
Lin, Yen-Ting
Liu, Yi-Nan
Shih, Jin-Yuan
Validation of Immunohistochemistry for the Detection of BRAF V600E-Mutated Lung Adenocarcinomas
title Validation of Immunohistochemistry for the Detection of BRAF V600E-Mutated Lung Adenocarcinomas
title_full Validation of Immunohistochemistry for the Detection of BRAF V600E-Mutated Lung Adenocarcinomas
title_fullStr Validation of Immunohistochemistry for the Detection of BRAF V600E-Mutated Lung Adenocarcinomas
title_full_unstemmed Validation of Immunohistochemistry for the Detection of BRAF V600E-Mutated Lung Adenocarcinomas
title_short Validation of Immunohistochemistry for the Detection of BRAF V600E-Mutated Lung Adenocarcinomas
title_sort validation of immunohistochemistry for the detection of braf v600e-mutated lung adenocarcinomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627826/
https://www.ncbi.nlm.nih.gov/pubmed/31234388
http://dx.doi.org/10.3390/cancers11060866
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