No conflicts of interest were declared.
A mouse model of basal-like breast carcinoma with metaplastic elements†
Version of Record online: 9 JAN 2007
Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 211, Issue 4, pages 389–398, March 2007
How to Cite
McCarthy, A., Savage, K., Gabriel, A., Naceur, C., Reis-Filho, J. and Ashworth, A. (2007), A mouse model of basal-like breast carcinoma with metaplastic elements. J. Pathol., 211: 389–398. doi: 10.1002/path.2124
- Issue online: 9 FEB 2007
- Version of Record online: 9 JAN 2007
- Manuscript Accepted: 10 NOV 2006
- Manuscript Revised: 6 NOV 2006
- Manuscript Received: 31 AUG 2006
- mouse model;
- basal breast cancer
Breast cancers arising in carriers of germline BRCA1 mutations frequently have a basal-like phenotype. Basal-like cancers are characterized by high histological grade, central necrotic areas, foci with metaplastic differentiation, lack of hormone receptor and HER2 (ErbB2) expression, and consistent positivity for basal markers, including CK5/6, CK14, and EGFR. We have used germline manipulation to generate a conditional mouse model of Brca1 deficiency. Transgenic expression of Cre recombinase in the mammary gland of these mice results in deletion of exons encoding the C-terminus of Brca1 and leads to tumour formation when combined with heterozygosity for a p53 mutation. Histologically, these mammary gland tumours were characterized by high histological grade, central necrotic areas, and presence of homologous metaplastic elements. These metaplastic elements consisted of neoplastic spindle cells or squamous cell differentiation in the form of keratin pearls or individual cell keratinization. Immunohistochemical analysis revealed expression of basal-like markers in all cases. The tumour phenotype generated in our mouse model was compared with published data on human basal-like breast carcinomas and also with metaplastic breast cancers with a basal-like phenotype; the comparison showed that we have generated a mouse model of basal-like breast cancer, which should prove useful in testing new and targeted treatments for this type of breast cancer. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.