Pilot assessment of vascular endothelial growth factor receptors and trafficking pathways in recurrent and metastatic canine subcutaneous mast cell tumours

Abstract

Canine subcutaneous mast cell tumour (scMCT) shows less aggressive biological behaviour than cutaneous MCT. Vascular endothelial growth factor receptor 2 (VEGFR2) is expressed by neoplastic cells in canine scMCT, but the relevance of this signalling pathway for disease pathobiology is not clear. The objective of this study was to quantify VEGF‐A, VEGFR2, pVEGFR2, the VEGF co‐receptor Neuropilin 1 (NRP‐1) and the E3 ubiquitin protein ligase c‐Cbl in canine scMCT, and to evaluate their association with disease outcome. Immunohistochemical staining for biomarkers was quantified from 14 cases of canine scMCT using manual and computer‐assisted methods. Kaplan–Meier curves were generated for disease‐free survival (DFS) and compared using Mantel–Cox log‐rank analysis. Cases with high levels of neoplastic cell VEGFR2, pVEGFR2 or c‐CBL immunoreactivity had significantly reduced DFS. All cases displayed neoplastic cells positive for VEGF‐A, which was significantly associated with pVEGFR2 immunoreactivity. There were also significant positive correlations between VEGFR2 and pVEGFR2, and between c‐CBL and pVEGFR2 levels. This pilot study demonstrates the potential utility of these markers in a subset of scMCT in dogs.

Allogeneic mesenchymal stem cell transplantation in healthy equine superficial digital flexor tendon: A study of the local inflammatory response

“…To determine the expression of the markers in the tendons of the animals, the whole section was evaluated; afterwards, five fields of each fragment with the greatest expression were selected. For CD172a and microvascular density (MVD -anti-factor VIII) evaluation, the percentage of stained cells was determined using the ImageJ program by establishing a "threshold" according to Da Silva et al (2017), which determined the percentage of stained cells. In addition, a grid reticle count of the field-stained lymphocytes was carried out for the CD3 antibody (a total of 5 fields per sample).…”

Morphological and Immunohistochemical Description of a Splenic Haemangioma in a Captive European Wolf (Canis lupus lupus) and a Review of the Current Literature

“…VEGFC and vascular endothelial growth factor D are both vascular endothelial growth factors (VEGFs) involved in the maintenance of normal adult endothelial cells, proliferation and the increase in vascular permeability and were found expressed by human vascular neoplastic cells [ 5 , 21 , 22 , 23 , 24 , 25 ]. In a previous study on canine vascular tumors, VEGFR-3 expression was found in the majority of hemagiosarcomas investigated, suggesting that this marker would not be suitable for the immunohistochemical discrimination between malignant and benign vascular tumors [ 26 , 27 , 28 ]. In contrast, the expression of VEGFC has been found limited to neoplastic endothelial cells in hemangiomas with capillary differentiation [ 3 ].…”

Investigation of Prognostic Value of Claudin-5, PSMA, and Ki67 Expression in Canine Splenic Hemangiosarcoma

“…For immunohistochemistry analysis, a qualitative evaluation describing each marker immunolocalization was performed. Immunohistochemical expression was evaluated using ImageJ software (ImageJ v1.47; NIH, Bethesda, MD, USA) according to the methods of Da Silva et al [21]. Briefly, a threshold tool was determined for Claudin-5 and PSMA expression based on positively stained cells.…”

“…Among the markers used in veterinary oncology, Ki-67 is a nuclear protein widely used for the evaluation of cell proliferation. This protein is expressed only in proliferating cells and in all active phases of the cell cycle, including early division, and observed mainly in patients at a late stage with poor prognosis [21]. Besides its importance in veterinary oncology, to the best of our knowledge, no previous study has reported the prognostic value of Ki67 in canine HSA.…”