EGFR amplification and lack of activating mutations in metaplastic breast carcinomas

Reis-Filho, J. S., Pinheiro, C., Lambros, M. B. K., Milanezi, F., Carvalho, S., Savage, K., Simpson, P. T., Jones, C., Swift, S., Mackay, A., Reis, R. M., Hornick, J. L., Pereira, E. M., Baltazar, F., Fletcher, C. D. M., Ashworth, A., Lakhani, S. R. and Schmitt, F. C. (2006) EGFR amplification and lack of activating mutations in metaplastic breast carcinomas. Journal of Pathology, 209 4: 445-453. doi:10.1002/path.2004

Author Reis-Filho, J. S.
Pinheiro, C.
Lambros, M. B. K.
Milanezi, F.
Carvalho, S.
Savage, K.
Simpson, P. T.
Jones, C.
Swift, S.
Mackay, A.
Reis, R. M.
Hornick, J. L.
Pereira, E. M.
Baltazar, F.
Fletcher, C. D. M.
Ashworth, A.
Lakhani, S. R.
Schmitt, F. C.
Title EGFR amplification and lack of activating mutations in metaplastic breast carcinomas
Formatted title
EGFR amplification and lack of activating mutations in
metaplastic breast carcinomas
Journal name Journal of Pathology   Check publisher's open access policy
ISSN 0022-3417
Publication date 2006
Sub-type Article (original research)
DOI 10.1002/path.2004
Volume 209
Issue 4
Start page 445
End page 453
Total pages 9
Editor S. C. Herrington
Place of publication Chichester
Publisher John Wiley
Collection year 2006
Language eng
Subject C1
321020 Pathology
730108 Cancer and related disorders
110316 Pathology (excl. Oral Pathology)
Abstract Metaplastic breast carcinomas are reported to harbour epidermal growth factor receptor (EGFR) overexpression in up to 80% of the cases, but EGFR gene amplification is the underlying genetic mechanism in around one-third of these. In this study, EGFR gene amplification as defined by chromogenic in situ hybridization and protein overexpression was examined in a cohort of 47 metaplastic breast carcinomas. Furthermore, the presence of activating EGFR mutations in exons 18, 19, 20, and 21 was investigated. Thirty-two cases showed EGFR overexpression and of these, 11 (34%) harboured EGFR gene amplification. In addition, EGFR amplification showed a statistically significant association with EGFR overexpression (p < 0.0094) and was restricted to carcinomas with homologous metaplasia. Ten cases, five with and five without EGFR amplification, were subjected to microarray-based CGH, which demonstrated that EGFR copy number gain may occur by amplification of a discrete genomic region or by gains of the short arm of chromosome 7 with a breakpoint near the EGFR gene locus, the minimal region of amplification mapping to EGFR, LANCL2, and SECOG. No activating EGFR mutations were identified, suggesting that this is unlikely to be a common alternative underlying genetic mechanism for EGFR expression in metaplastic breast carcinomas. Given that metaplastic breast carcinomas are resistant to conventional chemotherapy or hormone therapy regimens and that tumours with EGFR amplification are reported to be sensitive to EGFR tyrosine kinase inhibitors, these findings indicate that further studies are warranted to explore EGFR tyrosine kinase inhibitors as potential therapeutic agents for metaplastic breast carcinomas harbouring amplification of 7p11.2. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
Keyword Pathology
Breast Cancer
Chromogenic In Situ Hybridization
Gene Mutation
Growth-factor Receptor
Cell Lung-cancer
In-situ Hybridization
Tyrosine Kinase Inhibitors
Mammary Epithelial-cells
Basal-like Subtype
Myoepithelial Differentiation
Gene Amplification
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2007 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 127 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 144 times in Scopus Article | Citations
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Created: Wed, 15 Aug 2007, 07:56:39 EST