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-agenome
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.
