EGFR gene amplification in breast cancer: Correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations Journal Article

  

Authors:	Bhargava, R.; Gerald, W. L.; Li, A. R.; Pan, Q.; Lal, P.; Ladanyi, M.; Chen, B.
Article Title:	EGFR gene amplification in breast cancer: Correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations
Abstract:	The human epidermal growth factor receptor (HER) family of receptor tyrosine kinase has been extensively studied in breast cancer; however, systematic studies of EGFR gene amplification and protein overexpression in breast carcinoma are lacking. We studied EGFR gene amplification by chromogenic in situ hybridization (CISH) and protein expression by immunohistochemistry in 175 breast carcinomas, using tissue microarrays. Tumors with >5 EGFR gene copies per nucleus were interpreted as positive for gene amplification. Protein overexpression was scored according to standardized criteria originally developed for HER-2. EGFR mRNA levels, as measured by Affymetrix U133 Gene Chip microarray hybridization, were available in 63 of these tumors. HER-2 gene amplification by fluorescence in situ hybridization (FISH) and protein overexpression by immunohistochemistry were also studied, EGFR gene amplification (copy number range: 7-18; median: 12) was detected in 11/175 (6%) tumors, and protein overexpression was found in 13/175 (7%) tumors. Of the 11 tumors, 10 (91%) with gene amplification also showed EGFR protein overexpression (2+ or 3+ by immunohistochemistry). The EGFR mRNA level, based on Affymetrix U133 chip hybridization data, was increased relative to other breast cancer samples in three of the five tumors showing gene amplification. Exons 19 and 21 of EGFR, the sites of hotspot mutations in lung adenocarcinomas, were screened in the 11 EGFR-amplified tumors but no mutations were found. Three of these 11 tumors also showed HER-2 overexpression and gene amplification. Approximately 6% of breast carcinomas show EGFR amplification with EGFR protein overexpression and may be candidates for trials of EGFR-targeted antibodies or small inhibitory molecules. © 2005 USCAP, Inc All rights reserved.
Keywords:	immunohistochemistry; adult; human tissue; protein expression; aged; aged, 80 and over; middle aged; gene mutation; exon; mutation; adenocarcinoma; in situ hybridization, fluorescence; gene overexpression; breast cancer; gene amplification; gene expression; lung neoplasms; epidermal growth factor receptor; receptor, epidermal growth factor; protein tyrosine kinase; breast neoplasms; in situ hybridization; gene expression regulation, neoplastic; lung adenocarcinoma; fluorescence in situ hybridization; messenger rna; rna, messenger; breast carcinoma; tissue array analysis; receptor, erbb-2; cell nucleus; dna mutational analysis; tissue microarray; egfr; genetic screening; antibody; receptor gene; multigene family; oncogene neu; protein overexpression; mrna expression; chromogenic in situ hybridization
Journal Title:	Modern Pathology
Volume:	18
Issue:	8
ISSN:	0893-3952
Publisher:	Nature Research
Date Published:	2005-08-01
Start Page:	1027
End Page:	1033
Language:	English
DOI:	10.1038/modpathol.3800438
PUBMED:	15920544
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-24044520039&partnerID=40&md5=219c3f8e388ea33e2bb6264a28567091
Notes:	--- - "Cited By (since 1996): 111" - "Export Date: 24 October 2012" - "CODEN: MODPE" - "Source: Scopus"

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