The Relationship between Clinicopathological Features and Expression of Epithelial and Mesenchymal Markers in Spontaneous Canine Mammary Gland Tumors

Abstract

It is known that epithelial mesenchymal transition (EMT) contributes to the acquisition of malignant property in human cancers. However, the role of EMT in canine tumors remains to be elucidated. To evaluate the correlation between expression levels of protein markers involved in EMT and clinicopathological characteristics in canine mammary gland tumors, immunohistochemistry using antibodies against ZO-1, E-cadherin, vimentin, N-cadherin and fibronectin was performed on 119 clinical tissue samples. Consequently, loss of ZO-1 and E-cadherin, and gain of vimentin and N-cadherin were more frequently observed in malignant tumors than in benign tumors. However, there was no correlation among expression of these molecules. Univariate and multivariate analysis identified that loss of E-cadherin independently had a low one-year survival rate (adjusted odds ratio: 2.3, P=0.02). These results suggested that EMT might relate to acquisition of malignancy, and additionally, E-cadherin was strongly correlated with malignant behavior in canine mammary gland tumors.

Role of Annexin A2 in the EGF-induced epithelial-mesenchymal transition in human CaSki cells

“…EGF-R activation induces the epithelial-mesenchymal transition (EMT), which is accompanied by the overexpression of mesenchymal markers. In contrast, EGF-R inhibition, by a tyrosine kinase inhibitor or antibody, provokes EMT, which is accompanied by the upregulation of epithelial-marker proteins, such as E-cadherin (E-cad) and Zonula occludens-1 (5). The EMT is a multi-step process that includes dysfunctional cell-cell adhesive interactions, loss of cell-cell junctions and reorganization of the cytoskeleton, which is associated with cell proliferation, metastasis and immune escape.…”

“…E-cadherin binds to β-catenin and forms a protein complex that links to the actin cytoskeleton. E-cadherin has anti-proliferation, anti-invasion and anti-metastasis functions, and loss of E-cadherin contributes to metastatic dissemination in numerous cancer types (5). The mechanisms of E-cadherin loss in malignant cancers include genetic mutation, epigenetic silencing, transcription repression and proteolytic processes (4).…”

Co-localization of PTEN and E-cadherin in canine mammary hyperplasias and benign and malignant mammary tumors

“…Abnormal E-cadherin expression has been detected in several human carcinomas, such as digestive tract (Yun et al, 2014), urogenital (Li et al, 2011;Keck et al, 2013;Chang et al, 2014), lung (Bremnes et al, 2002) and cervical (Li et al, 2011) carcinomas. In canine oncology, E-cadherin expression has been investigated in several cancers and particularly in colorectal (Aresu et al, 2010), Merkel cell (Gil da Costa et al, 2010), testicular (Ciaputa et al, 2014), prostate (Fonseca-Alves et al, 2013) oral squaqmous cell (Mestrinho et al, 2014) and thyroid (Campos et al, 2014) carcinomas and tumors, in mammary tumours (Brunetti et al, 2003, Gama andSchmitt 2012;Yoshida et al, 2014), These reports confirmed E-cadherin membranous immunolocalization as the normal expression (Sarli et al, 2004), while cytoplasmic and nuclear location are linked to a downregulation of its tumor suppressor role (Chetty and Serra, 2008).…”

Influence of E‐cadherin genetic variation in canine mammary tumour risk, clinicopathological features and prognosis

“…Several immunohistochemical studies reported decreased E‐cadherin membrane expression, as well as E‐cadherin cytoplasmic internalization, in canine mammary carcinomas . These features have been linked to aggressive clinicopathological characteristics of mammary carcinomas, such as high histological grade and mitotic index, larger tumour size, infiltrative or invasive growth and lymph node metastasis .…”

“…These features have been linked to aggressive clinicopathological characteristics of mammary carcinomas, such as high histological grade and mitotic index, larger tumour size, infiltrative or invasive growth and lymph node metastasis . Besides, some authors found a significant association between E‐cadherin down expression and shorter disease‐free survival and OS . Recently, gene expression profiling research documented significant differences between metastatic and non‐metastatic canine mammary tumours (CMTs), with some authors linking the loss of cell adhesion molecules to the metastatic subgroup .…”