Assessment of EGFR mutation status in lung adenocarcinoma by immunohistochemistry using antibodies specific to the two major forms of mutant EGFR Journal Article

   

Authors:	Brevet, M.; Arcila, M.; Ladanyi, M.
Article Title:	Assessment of EGFR mutation status in lung adenocarcinoma by immunohistochemistry using antibodies specific to the two major forms of mutant EGFR
Abstract:	EGFR mutations are the best predictors of response to EGFR kinase inhibitors in lung adenocarcinoma. We evaluated two mutation-specific monoclonal antibodies for the detection of EGFR mutations by immunohistochemistry (IHC), generated respectively against the L858R mutant and the exon 19 mutant with the common 15bp/5AA deletion. These two mutations account for approximately 90% of all EGFR mutations. IHC staining performed on 218 paraffin-embedded lung adenocarcinomas was assessed on a 0 to 3+ scale, and positivity cutoffs of 1+ and 2+ were compared. All cases were studied by standard molecular methods for these two mutations, and selected cases were also studied using higher sensitivity molecular assays. The EGFR L858R mutant antibody showed a sensitivity of 95% and a positive predictive value (PPV) of 99% with a positivity cutoff of 1+ and a sensitivity of 76% and a PPV of 100% with a positivity cutoff of 2+. The EGFR exon 19 mutant - specific antibody showed reduced sensitivity for exon 19 deletions other than 15bp. A positivity cutoff of 1+ resulted in a sensitivity of 85% and a PPV of 99%, whereas a 2+ cutoff gave a sensitivity of 67% and a PPV of 100%. IHC with EGFR mutant - specific antibodies could be used as a screen to identify most candidates for EGFR inhibitors. Copyright © American Society for Investigative Pathology and the Association for Molecular Pathology.
Keywords:	immunohistochemistry; human tissue; gene deletion; mutation; exons; mutant protein; adenocarcinoma; mass spectrometry; animals; gene; lung neoplasms; epidermal growth factor receptor; receptor, epidermal growth factor; mutational analysis; lung adenocarcinoma; amino acid sequence; molecular sequence data; diagnostic value; antibodies; egfr gene; epidermal growth factor receptor antibody
Journal Title:	Journal of Molecular Diagnostics
Volume:	12
Issue:	2
ISSN:	1525-1578
Publisher:	Elsevier Science, Inc.
Date Published:	2010-03-01
Start Page:	169
End Page:	176
Language:	English
DOI:	10.2353/jmoldx.2010.090140
PUBMED:	20093391
PROVIDER:	scopus
PMCID:	PMC2871723
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-77649140830&partnerID=40&md5=05a2c068b73104116f6269dc34eea685
Notes:	--- - "Cited By (since 1996): 13" - "Export Date: 20 April 2011" - "CODEN: JMDIF" - "Source: Scopus"

https://synapse.mskcc.org/synapse/works/has_related_data_chk/3751