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False-positive EGFR Mutation-specific Immunohistochemistry in HER2-positive Breast Cancers: A Potential Diagnostic Pitfall

False-positive EGFR Mutation-specific Immunohistochemistry in HER2-positive Breast Cancers: A... To the Editor: We read with interest the article, “Cross-reactivity of EGFR mutation-specific immunohistochemistry assay in HER2-positive tumors” in your journal (November 11, 2014). We can support the findings of this article in a large cohort of cases. Reflex mutation testing for activating mutations in the tyrosine kinase domain of EGFR (exons 18 to 21) is now a standard of care for all patients with advanced or recurrent nonsquamous non–small cell lung cancer. Mutation-specific immunohistochemistry (IHC) for the 2 most common mutations in EGFR—an in-frame deletion in exon 19 (delE746-A750) and a missense mutation in exon 21 (L858R)—can be a useful adjunct to formal molecular testing, particularly to identify false-negative molecular tests, or to be used on cases with minimal tissue available which may be inadequate for molecular testing. 1,2 Most investigators report that mutation-specific IHC is highly specific for the presence of a pathogenic mutation, however, it shows limited sensitivity, and as such it cannot replace formal molecular testing. 1,2 We recently received a fine needle aspiration biopsy from a patient with a lung mass. At the time of receipt we were unaware that the patient had a history of HER2-amplified breast carcinoma. The adenocarcinoma cells demonstrated http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Applied Immunohistochemistry & Molecular Morphology Wolters Kluwer Health

False-positive EGFR Mutation-specific Immunohistochemistry in HER2-positive Breast Cancers: A Potential Diagnostic Pitfall

False-positive EGFR Mutation-specific Immunohistochemistry in HER2-positive Breast Cancers: A Potential Diagnostic Pitfall


To the Editor: We read with interest the article, “Cross-reactivity of EGFR mutation-specific immunohistochemistry assay in HER2-positive tumors” in your journal (November 11, 2014). We can support the findings of this article in a large cohort of cases. Reflex mutation testing for activating mutations in the tyrosine kinase domain of EGFR (exons 18 to 21) is now a standard of care for all patients with advanced or recurrent nonsquamous non–small cell lung cancer. Mutation-specific immunohistochemistry (IHC) for the 2 most common mutations in EGFR—an in-frame deletion in exon 19 (delE746-A750) and a missense mutation in exon 21 (L858R)—can be a useful adjunct to formal molecular testing, particularly to identify false-negative molecular tests, or to be used on cases with minimal tissue available which may be inadequate for molecular testing. 1,2 Most investigators report that mutation-specific IHC is highly specific for the presence of a pathogenic mutation, however, it shows limited sensitivity, and as such it cannot replace formal molecular testing. 1,2 We recently received a fine needle aspiration biopsy from a patient with a lung mass. At the time of receipt we were unaware that the patient had a history of HER2-amplified breast carcinoma. The adenocarcinoma cells demonstrated diffuse strong positive staining with EGFR exon 21 (L858S) mutation-specific IHC, but were negative for EGFR exon 19 mutation-specific IHC, TTF1, ER, PR, and Napsin A. After obtaining the additional clinical history, we demonstrated that the tumor was positive for breast markers (mammoglobin, GATA3) and both HER2 amplified by silver in-situ hybridization and positive for HER2 expression by IHC. We therefore concluded that this represented metastatic HER2-positive breast carcinoma to the lung. In view of the positive staining with EGFR exon 21 mutation-specific IHC, we performed mutation testing by matrix-assisted laser desorption/ionization-time of flight...
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References (4)

Copyright
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Subject
Letter to the Editor
ISSN
1541-2016
eISSN
1533-4058
DOI
10.1097/PAI.0000000000000272
pmid
26574631
Publisher site
See Article on Publisher Site

Abstract

To the Editor: We read with interest the article, “Cross-reactivity of EGFR mutation-specific immunohistochemistry assay in HER2-positive tumors” in your journal (November 11, 2014). We can support the findings of this article in a large cohort of cases. Reflex mutation testing for activating mutations in the tyrosine kinase domain of EGFR (exons 18 to 21) is now a standard of care for all patients with advanced or recurrent nonsquamous non–small cell lung cancer. Mutation-specific immunohistochemistry (IHC) for the 2 most common mutations in EGFR—an in-frame deletion in exon 19 (delE746-A750) and a missense mutation in exon 21 (L858R)—can be a useful adjunct to formal molecular testing, particularly to identify false-negative molecular tests, or to be used on cases with minimal tissue available which may be inadequate for molecular testing. 1,2 Most investigators report that mutation-specific IHC is highly specific for the presence of a pathogenic mutation, however, it shows limited sensitivity, and as such it cannot replace formal molecular testing. 1,2 We recently received a fine needle aspiration biopsy from a patient with a lung mass. At the time of receipt we were unaware that the patient had a history of HER2-amplified breast carcinoma. The adenocarcinoma cells demonstrated

Journal

Applied Immunohistochemistry & Molecular MorphologyWolters Kluwer Health

Published: Mar 1, 2016

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