Abstract
Epithelial-mesenchymal transition (EMT) is defined as switching of polarized epithelial cells to a migratory fibroblastoid phenotype. EMT is known to be involved in the progression and metastasis of various cancers in humans, but this specific process is still little explored in the veterinary literature. The aim of this research was to evaluate the expression of EMT-related proteins in canine mammary carcinomas (CMCs). The expression of six EMT-related proteins in 94 CMCs of female dogs was evaluated by immunohistochemistry using a tissue array method. Additionally, clinicopathological characteristics were compared with the expression of EMT-related proteins. Loss of epithelial protein and/or acquisition of the expression of mesenchymal proteins were observed in CMCs. Loss of epithelial protein and/or acquisition of the expression of mesenchymal proteins were observed, particularly in tumors with evidence of stromal invasion; however, significance was only observed between the S100A4 and vascular invasion. In addition, Snai-1 nuclear immunoexpression was significantly related to E-cadherin loss. In conclusion, loss of epithelial proteins and/or the acquisition of mesenchymal proteins are associated with EMT and may have an important role in the evaluation of CMC patients. The unique immunoexpression pattern of Snai-1 could help to distinguish between an adenoma and a non-metastatic carcinoma and seems to be related to conversion of myoepithelial cells to a complete mesenchymal-like phenotype. Loss of E-cadherin and cytokeratin and change of immunoexpression pattern of Snai-1, N-cadherin, S100A4 and MMP-2 indicate the occurrence of EMT in canine mammary carcinomas and should result in an en bloc resection or a close follow-up.
Highlights
Mammary gland tumors are the most common neoplasms of the female dog and represent a remarkably heterogeneous group in terms of morphology and biological behavior [1]
The process of cancer metastasis appears to be regulated by a variety of gene products, little is known about the molecular aspects of progression of canine mammary carcinoma (CMC) cells
An important aspect of epithelial-mesenchymal transition (EMT) is the loss of epithelial protein markers, i.e. cytokeratins and E-cadherin
Summary
Mammary gland tumors are the most common neoplasms of the female dog and represent a remarkably heterogeneous group in terms of morphology and biological behavior [1]. The conversion of epithelial cells to migratory fibroblastoid cells—known as epithelial-mesenchymal transition (EMT)—was suggested to be involved in metastasis. During EMT, cells lose epithelial polarity and acquire a spindle-shaped, highly motile mesenchymallike phenotype This transition involves loss or redistribution of tight- and adherencejunction proteins and a switch to mesenchymal gene expression which confers upon cells the ability to pass through the basement membrane [3]. This phenomenon is reactivated during the progression of numerous cancers and was demonstrated to be associated with poor histological differentiation, local invasiveness and distant metastasis [4] [5]
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