title: The dog as a natural animal model for study of the mammary myoepithelial basal cell lineage and its role in mammary carcinogenesis.
abstract: Basal-like tumours constitute 2-18% of all human breast cancers (HBCs). These tumours have a basal myoepithelial phenotype and it has been hypothesized that they originate from either myoepithelial cells or mammary progenitor cells. They are heterogeneous in morphology, clinical presentation, outcome and response to therapy. Canine mammary carcinomas (CMCs) have epidemiological and biological similarities to HBCs, are frequently biphasic and are composed of two distinct neoplastic populations (epithelial and myoepithelial). The present study evaluates the potential of CMCs as a natural model for basal-like HBCs. Single and double immunohistochemistry was performed on serial sections of 10 normal canine mammary glands and 65 CMCs to evaluate expression of cytokeratin (CK) 8/18, CK5, CK14, α-smooth muscle actin (SMA), calponin (CALP), p63 and vimentin (VIM). The tumours were also evaluated for Ki67 and human epidermal growth factor receptor (HER)-2 expression. A hierarchical model of cell differentiation was established, similar to that for the human breast. We hypothesized that progenitor cells (CK5(+), CK14(+), p63(+) and VIM(+)) differentiate into terminally-differentiated luminal glandular (CK8/18(+)) and myoepithelial (CALP(+), SMA(+) and VIM(+)) cells via intermediary luminal glandular cells (CK5(+), CK14(+) and CK8/CK18(+)) and intermediary myoepithelial cells (CK5(+), CK14(+), p63(+), SMA(+), CALP(+) and VIM(+)). Neoplastic myoepithelial cells in canine complex carcinomas had labelling similar to that of terminally-differentiated myoepithelial cells, while those of carcinomas-and-malignant myoepitheliomas with a more aggressive biological behaviour (i.e. higher frequency of vascular/lymph node invasion and visceral metastases and higher risk of tumour-related death) were comparable with intermediary myoepithelial cells and had significantly higher Ki67 expression. The majority of CMCs examined were negative for expression of HER-2. The biphasic appearance of CMCs with involvement of the myoepithelial component in different stages of cell differentiation may help to define the role of myoepithelial cells in the mammary carcinogenetic process and the heterogeneous nature of basal-like HBCs.
authors: Pathology Department, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK. Electronic address: robertarasotto@yahoo.it.
authors: R
authors: R
authors: Rasotto
authors: Laboratory of Pathology and Toxicology, Department of Pathobiology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA.
authors: M H
authors: MH
authors: Goldschmidt
authors: Department of Comparative Biomedicine and Food Science, University of Padova, Viale dell'università 16, 35020 Legnaro, Padova, Italy.
authors: M
authors: M
authors: Castagnaro
authors: Department of Comparative Biomedicine and Food Science, University of Padova, Viale dell'università 16, 35020 Legnaro, Padova, Italy.
authors: P
authors: P
authors: Carnier
authors: Department of Comparative Biomedicine and Food Science, University of Padova, Viale dell'università 16, 35020 Legnaro, Padova, Italy.
authors: D
authors: D
authors: Caliari
authors: Department of Comparative Biomedicine and Food Science, University of Padova, Viale dell'università 16, 35020 Legnaro, Padova, Italy.
authors: V
authors: V
authors: Zappulli
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D019070:Cell Lineage; D004195:Disease Models, Animal; D004285:Dogs; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology*; D009130:Muscle, Smooth / Q000473:pathology; D009208:Myoepithelioma / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: basal-like breast cancer; dog; mammary gland; myoepithelial cells