1. ¹Department of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan
2. ²Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan
3. ³Institute of Medical Research, Chang Jung Christian University, Tainan, Taiwan
4. ⁴Welgene Biotech. Co. Ltd, Taipei, Taiwan
5. ⁵Center for Systems Biology and Bioinformatics, National Taiwan University, Taipei, Taiwan
6. ⁶Department of Life Science, National Taiwan University, Taipei, Taiwan
7. ⁷Department of Surgery, College of Medicine, National Taiwan University, Taipei, Taiwan
8. ⁸Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan
9. ⁹Department of Molecular and Cellular Oncology, University of Texas, MD Anderson Cancer Center, TX, USA
10. ¹⁰Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan

Correspondence: Dr KJ Chang, Department of Surgery, College of Medicine, National Taiwan University, 1-1 Jen-Ai Road, Taipei, Taiwan or Dr FJ Hsieh, Department of Obstetrics and Gynecology, National Taiwan University, College of Medicine, 1-1 Jen-Ai Road, Taipei 104, Taiwan. E-mail: kingjen@ha.mc.ntu.edu.tw or fjhsieh@ha.mc.ntu.edu.tw

¹¹These authors have contributed equally to this work.

Received 7 February 2007; Revised 8 May 2007; Accepted 15 May 2007; Published online 2 July 2007.

Abstract

Metaplastic carcinoma of the breast (MCB) is a poorly understood subtype of breast cancer. It is generally characterized by the coexistence of ductal carcinomatous and transdifferentiated sarcomatous components, but the underlying molecular alterations, possibly related to epithelial–mesenchymal transition (EMT), remain elusive. We performed transcriptional profiling using half-a-genome oligonucleotide microarrays to elucidate genetic profiles of MCBs and their differences to those of ductal carcinoma of breasts (DCBs) using discarded specimens of four MCBs and 34 DCBs. Unsupervised clustering disclosed distinctive expression profiles between MCBs and DCBs. Supervised analysis identified gene signatures discriminating MCBs from DCBs and between MCB subclasses. Notably, many of the discriminator genes were associated with downregulation of epithelial phenotypes and with synthesis, remodeling and adhesion of extracellular matrix, with some of them have known or inferred roles related to EMT. Importantly, several of the discriminator genes were upregulated in a mutant Snail-transfected MCF7 cell known to exhibit features of EMT, thereby indicating a crucial role for EMT in the pathogenesis of MCBs. Finally, the identification of SPARC and vimentin as poor prognostic factors reinforced the role of EMT in cancer progression. These data advance our understanding of MCB and offer clues to the molecular alterations underlying EMT.