Abstract
BackgroundThe molecular-based classification of canine mammary carcinomas (CMCs) has been the focus of much current research. Both in canines and humans, the triple-negative (TN) molecular subtype of mammary cancer is defined by a lack of expression of progesterone receptor (PR), oestrogen receptor (ER) and HER2. It has a poor prognosis; no effective targeted therapy is available. Vitamin D displays anticarcinogenic properties, and the expression of its receptor (VDR) has been found in different molecular subtypes, being about 30–40 % of TN breast cancer (TNBC) positive to it. We assessed the VDR expression in the different molecular subtypes of 58 CMCs from 45 female dogs using an immunohistochemical panel for the molecular classification of included: PR, ER, HER2, cytokeratin (CK) 5, CK14, and Ki67. In addition, we studied the relationship among the molecular subtypes of CMCs and clinicopathologic parameters.ResultsInvestigation showed VDR positivity in 45.0 % of the triple-negative CMCs (TNCMCs), 27.3 % of luminal B and 19.0 % of luminal A. Luminal A was the most molecular subtype represented of the total tumours (36.2 %), followed of TNCMCs (34.5 %), luminal B (20.7 %) and HER2-overexpression (10.3 %). Both HER2-overexpression and TNCMC subtypes were positively related to lymphatic invasion (P = 0.028), simple histologic subtype (P = 0.007), a higher histological grade (P = 0.045) and a trend to higher proliferation index (P = 0.09).ConclusionsThe highest VDR expression was observed in TNCMC, being almost half of them (45 %) positive to this receptor. VDR expression was absent in HER2-overexpression tumours and low in luminal A and B molecular subtypes.
Highlights
The molecular-based classification of canine mammary carcinomas (CMCs) has been the focus of much current research
Canine mammary carcinomas (CMCs) are the most common neoplasm in female dogs and between 40 and 60 % of these tumours are malignant depending on the study [5]
According to the histologic subtype assessed by histology [haematoxylin and eosin (HE) stains], the complex was the more frequent subtype (27/58 cases, 46.6 %), followed by simple (21/58 cases, 36.2 %), and mixed (10/ 58 cases, 17.2 %)
Summary
The molecular-based classification of canine mammary carcinomas (CMCs) has been the focus of much current research Both in canines and humans, the triple-negative (TN) molecular subtype of mammary cancer is defined by a lack of expression of progesterone receptor (PR), oestrogen receptor (ER) and HER2. The percentage of this type of TN mammary cancer (triple-negative canine mammary carcinoma, TNCMC) amongst all CMCs varies widely between authors (18.7–76.3 %) [9, 11] Both in humans and canines, TN mammary tumours (TNBC and TNCM C respectively) have a more aggressive phenotype, a higher rate of relapse and poorer prognosis than other mammary cancer types [9, 12,13,14,15,16]. TNBC is not treated with specific target therapies [13]; as such, it is important to explore novel therapeutic options for patients with this disease
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