EGFRamplification and lack of activating mutations in metaplastic breast carcinomas

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Abstract

Metaplastic breast carcinomas are reported to harbour epidermal growth factor receptor (EGFR) overexpression in up to 80% of the cases, butEGFRgene amplification is the underlying genetic mechanism in around one-third of these. In this study,EGFRgene amplification as defined by chromogenicin situhybridization and protein overexpression was examined in a cohort of 47 metaplastic breast carcinomas. Furthermore, the presence of activatingEGFRmutations in exons 18, 19, 20, and 21 was investigated. Thirty-two cases showed EGFR overexpression and of these, 11 (34%) harbouredEGFRgene amplification. In addition,EGFRamplification 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 withoutEGFRamplification, were subjected to microarray-based CGH, which demonstrated thatEGFRcopy 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 theEGFRgene locus, the minimal region of amplification mapping toEGFR, LANCL2, andSEC61G. No activatingEGFRmutations 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 withEGFRamplification 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 © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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