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Received May 4, 2012; Accepted Jun 19, 2012
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
Mammary gland tumors of dogs are formed by both epithelial (epithelium and myoepithelium) and mesenchymal components. The origin of the mesenchymal cells is still debated. The elevated frequency of tumors showing myoepithelial or basal cell proliferation is a unique feature of canine mammary tumors [1].
In the normal mammary gland, the lumina are delimitated by an inner layer of polarized epithelial cells resting on two outer or basal layers of epithelial and myoepithelial cells [2]. Both basal and myoepithelial cells synthesize the basement membrane of ducts and alveoli and form a structural barrier between the luminal epithelial cells and the surrounding stroma [3]. In ducts, myoepithelial cells form a nearly continuous layer of cells oriented parallel to the long axis of the ducts. This layer surrounds the luminal epithelial cells and separates them from the basement membrane and the stroma. In alveoli, the myoepithelial cells are discontinuous, forming a basket-like network around the alveoli, allowing some luminal epithelial cells to contact the basement membrane directly [3–5]. Therefore, the myoepithelium is not only located in an ideal position to communicate between these two compartments, but it is also positioned to provide important regulatory signals for the maintenance of normal cell structure [5].
Based on immunohistochemistry, the three layers of cells of the normal mammary gland display different markers: the luminal epithelium is labeled by CK19, and the basal cells and myoepithelial cells are stained by CK5/6 [6] and CK14 [2] and p63, Alpha-SMA, and VIM [2]. Myoepithelial cells are contractile elements exhibiting a combined epithelial and smooth muscle immunoprofile. The markers mentioned above are expressed in the cytoplasm, except for p63 which is a nuclear marker [1]. The myoepithelial cell layer is the sole source of tumor suppressor p63, which is significantly inhibited on proliferation and invasion of associated tumor cells [7]. In addition, basal myoepithelial cells in the normal mammary gland are occasionally labeled by ER antibody [8], which is used for the molecular-based classification of canine mammary tumors [9, 10].
Distinct myoepithelial cell...