THE DOG AS A SPONTANEOUS MODEL TO STUDY THE MAMMARY MYOEPITHELIAL BASAL CELL LINEAGE AND ITS ROLE IN MAMMARY CARCINOGENESIS

Introduction: Basal-like human breast cancers (HBCs) are hypothesized to originate from either myoepithelial or mammary progenitor cells. They are heterogeneous in morphology and outcome. To better understand their biology, the study of cell lineages of the normal human breast has assumed increasing importance. This work evaluated the potential of canine mammary carcinomas (CMCs) as a spontaneous model for basal-like HBCs. Materials and Methods: Single and double immunohistochemical analyses were performed on serial sections of 10 normal canine mammary glands and 65 CMCs for CK8/18, CK5, CK14, a-smooth muscle actin (SMA), calponin, p63 and vimentin. Ki67 and HER-2 were also evaluated in CMCs. Results: Previously unrecognized cell subpopulations were identified in the normal canine mammary gland: progenitor cells (CK5+, CK14+, p63+ and vimentin+), intermediary luminal glandular cells (CK5+, CK14+ and CK8/CK18+), intermediary myoepithelial cells (CK5+,CK14+, p63+, SMA+, calponin+and vimentin+), and terminally differentiated luminal glandular (CK8/18+) and myoepithelial (calponin+, SMA+ and vimentin+) cells. Myoepithelial cells of complex carcinomas were immunohistochemically similar to terminally differentiated myoepithelial cells, while those of carcinomas and malignant myoepitheliomas (that had a poorer prognosis), were comparable to intermediary myoepithelial cells and had higher Ki67 expression. Conclusions: The biphasic appearance of CMCs with involvement of the myoepithelium in different stages of cell differentiation may help to define the role of myoepithelial cells in mammary carcinogenesis and the heterogeneous nature of basal-like HBCs.