Vitamin D receptor (VDR) expression in different molecular subtypes of canine mammary carcinoma

Abstract

Background 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. 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. Results Investigation 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). Conclusions The 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.

Comparison of serum 25(OH) vitamin D, parathormone and immunity marker concentrations between dogs with transmissible venereal tumour and healthy dogs

“…The primary aim of this study was to compare serum 25(OH)D concentrations between dogs with TVT and healthy dogs. As has been found in dogs with other cancers (Davies et al, 2012;Nascimento-hama et al, 2022;Russell et al, 2010;Sánchez-Céspedes et al, 2021;, the results demonstrated that serum 25(OH)D concentrations were significantly lower in dogs with TVT than in healthy dogs.…”

Analysis of cell-free DNA concentration, fragmentation patterns and TP53 gene expression in mammary tumor-bearing dogs: A pilot study

“…The histological diagnosis was confirmed on hematoxylin and eosin (H&E)-stained full-sections by two independent pathologists (YMR and RSC) according to Zapulli et al ( 27 ). In addition, assessment of tumor inflammatory cell infiltration and presence of necrosis within the tumor (yes/no) was performed on H&E-stained full sections ( 28 ).…”

“…For molecular classification of canine mammary carcinomas (CMC), the classification previously described by Sánchez-Céspedes et al ( 28 ) was used. Immunostaining of anti-HER2, -PR, -ER, -CK5, -CK14, and Ki67 were semi-quantitatively analyzed based on the intensity and percentage of positive tumor cells.…”

“…For the IHC evaluation of CK5 and CK14 expression, both epithelial and myoepithelial cells (when presented in complex and mixed tumors), 10 randomly selected fields were evaluated. Cases with ≥10 % of positive tumor cells, without considering the residual/pre-existing myoepithelial cells, and with strong cytoplasmic staining were considered to be positive ( 28 ). Ki67 expression was used to determine the proliferation index (PI).…”

“…The PI was expressed as the percentage of positively-labeled cells. A minimum of 1,000 tumor cells were counted per case ( 28 ).…”