Expression of VEGFR and PDGFR‐α/‐βin 187 canine nasal carcinomas

Abstract

Radiotherapy represents the standard of care for intranasal carcinomas. Responses to tyrosine kinase inhibitors (TKIs) have been reported but data on expression of target receptor tyrosine kinases (rTKs) is limited. This study characterizes the expression of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR)-α and PDGFR-β in canine intranasal carcinomas. Histological samples from 187 dogs were retrieved. Immunohistochemistry was performed using commercially available antibodies. Expression of rTKs was classified into weak, moderate or intense and additionally recorded as cytoplasmic, membranous, cytoplasmic-membranous, nuclear or stromal. VEGFR was expressed in 158 dogs with predominantly moderate expression (36.9%) and a cytoplasmic-membranous expression pattern (70.9%). PDGFR-α was detected in 133 with predominantly weak expression (57.9%) and cytoplasmic pattern (87.9%). PDGFR-β was identified in 74 patients with a predominantly moderate expression (17.6%) and cytoplasmic expression pattern (63.5%). Co-expression of rTKs was common. These results confirm expression of VEGFR, PDGFR-α and PDGFR-β in canine intranasal carcinomas and support the utility of TKIs.

The role of toceranib phosphate in dogs with non‐mast cell neoplasia: A systematic review

“…Canine nasal carcinomas have been shown to express rTKs including KIT and PDGFRα/β, 17 however the lack of phosphorylated target rTKs suggests that toceranib may exert its clinical effects via a different, unidentified mechanism 62 . Seven dogs were treated with toceranib in the previously mentioned study by London et al 28 Of the two dogs that were re‐imaged, 1 had a CR and 1 had SD and an additional 3 dogs experienced improvement in the clinical signs for an overall CB rate of 71.4% 28 .…”

“…Numerous studies over the last 15 years have demonstrated that a wide array of canine tumours overexpress many of the tyrosine kinases that are targets for these drugs, including KIT, PDGFR and VEGFR. [12][13][14][15][16][17] The majority of these studies focus of toceranib phosphate, rather than masitinib mesylate, likely due to the availability of the former. The aim of this review was to therefore examine the evidence for treatment of non-mast cell tumours in dogs with toceranib phosphate.…”

Receptor tyrosine kinase expression and phosphorylation in canine nasal carcinoma

“…30,31 Stromal expression of PDGFR-b was present in all samples analyzed in this study whereas previous studies have shown only 60.9% of samples to have stromal staining for PDGFR-b. 13 The development and function of vessels in the TME rely heavily on PDGFR-b and inhibition of this RTK in the TME has been documented in some human solid tumors and may represent an indirect target for toceranib in canine nasal carcinomas. 30,32,33 Interestingly, VEGFR2 and PDGFR-a were not expressed in the tumor stroma in this study; however, PDGFR-a was shown to have nuclear localization.…”

“…9,12 Several RTK targets of toceranib expressed by canine nasal carcinomas are responsible for angiogenic sprouting and vascular maturation, both defined processes in vasculogenesis and angiogenesis that are imperative for tumor growth. 9,[12][13][14] In one report of 187 dogs with nasal carcinoma, VEGFR was detected in 84.5%, PDGFR-a in 71.1%, and PDGFR-b in 39.6% of tumors by immunohistochemistry. 13 While VEGFR was expressed in the majority of these canine nasal carcinomas, another report showed that 91.7% of epithelial nasal tumors also expressed the VEGF ligand.…”

“…9,[12][13][14] In one report of 187 dogs with nasal carcinoma, VEGFR was detected in 84.5%, PDGFR-a in 71.1%, and PDGFR-b in 39.6% of tumors by immunohistochemistry. 13 While VEGFR was expressed in the majority of these canine nasal carcinomas, another report showed that 91.7% of epithelial nasal tumors also expressed the VEGF ligand. 14 Additionally, one report of dogs with solid tumors treated with toceranib identified significantly increased plasma VEGF level, a surrogate marker for VEGFR2 inhibition, denoting a possible anti-angiogenic effect.…”