Autor(es):
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.
Data: 2006
Identificador Persistente: http://hdl.handle.net/1822/5747
Origem: RepositóriUM - Universidade do Minho
Assunto(s): Breast cancer; Gaene mutation; Chromogenic in situ hybridization; Microarrays; Immunohistochemistry
Descrição
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.
