title: Receptor Tyrosine Kinase Expression Profiles in Canine Cutaneous and Subcutaneous Mast Cell Tumors.
abstract: The receptor tyrosine kinase (RTK) KIT is a major focus of current research into canine mast cell tumors (MCTs). Little is known about the role of other RTKs, such as vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs). These RTKs are dysregulated in many human and animal cancers and are key regulators of tumor angiogenesis. The aims of this study were to assess the expression and activation (phosphorylation) status of KIT, VEGFR2, and PDGFR (α and β) in canine MCTs and to examine associations with various clinical outcomes. c-KITmutational status and KIT cellular localization pattern were also evaluated for these tumors. Twenty-seven MCTs, consisting of 5 subcutaneous and 22 cutaneous tumors, from 25 dogs were evaluated. MCT biopsies, cultured mast cells, and skin from the surgical margin were analyzed through Western blotting. MCT biopsies were also used for KIT immunohistochemical labeling and polymerase chain reaction for c-KITmutational analysis. MCT had heterogeneous expression profiles for all 3 RTKs, which varied in intensity and activation status. Statistical analyses showed phosphorylated KIT, VEGFR2, and KIT cellular localization to be predictive of decreased survival time, disease-free interval, and increased metastatic rate. Expression of VEGFR2 and KIT diffuse cytoplasmic labeling were also significantly associated with increased rate of local recurrence. The results of the study show that phosphorylated KIT, KIT, VEGFR2, and PDGFRβ, in addition to KIT localization, may be valuable prognostic determinants in MCTs and should be further studied to improve diagnostic and therapeutic modalities.
authors.affiliation: University of Guelph, Ontario Veterinary College, Guelph, Canada.
authors.forename: J J
authors.initials: JJ
authors.lastname: Thompson
authors.affiliation: University of Guelph, Ontario Veterinary College, Guelph, Canada.
authors.forename: J A
authors.initials: JA
authors.lastname: Morrison
authors.affiliation: University of Guelph, Ontario Veterinary College, Guelph, Canada.
authors.forename: D L
authors.initials: DL
authors.lastname: Pearl
authors.affiliation: University of Guelph, Ontario Veterinary College, Guelph, Canada University of Florida, Gainesville, FL, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Boston
authors.affiliation: University of Guelph, Ontario Veterinary College, Guelph, Canada.
authors.forename: G A
authors.initials: GA
authors.lastname: Wood
authors.affiliation: University of Guelph, Ontario Veterinary College, Guelph, Canada.
authors.forename: R A
authors.initials: RA
authors.lastname: Foster
authors.affiliation: University of Guelph, Ontario Veterinary College, Guelph, Canada bcoomber@uoguelph.ca.
authors.forename: B L
authors.initials: BL
authors.lastname: Coomber
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004283:Dog Diseases / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D004285:Dogs; D005260:Female; D008297:Male; D008407:Mast Cells / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000175:diagnosis / Q000201:enzymology / Q000473:pathology / Q000662:veterinary*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases
keywords: PDGFR; VEGFR; c-KIT; dog; mast cell tumor; receptor tyrosine kinase; survival