Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/5747

TitleEGFR amplification and lack of activating mutations in metaplastic breast carcinomas
Author(s)Reis Filho, Jorge S.
Pinheiro, Céline
Lambros, M. B. K.
Milanezi, Fernanda
Carvalho, Silvia
Savage, K.
Simpson, Pete T.
Jones, C.
Swift, S.
Mackay, A.
Reis, R. M.
Hornick, J. L.
Pereira, Emílio M.
Baltazar, Fátima
Fletcher, C. D. M.
Ashworth, A.
Lakhani, Sunil R.
Schmitt, Fernando C.
KeywordsBreast cancer
Gaene mutation
Chromogenic in situ hybridization
Microarrays
Immunohistochemistry
gene mutation
Issue dateAug-2006
PublisherWiley
JournalJournal of Pathology
Citation"Journal of pathology". ISSN 1096-9896. 209:4 (Aug. 2006) 445-453.
Abstract(s)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 microarraybased 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 SEC61G. 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.
TypeArticle
URIhttp://hdl.handle.net/1822/5747
DOI10.1002/path.2004
ISSN1096-9896
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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