title: Expression of Phosphorylated KIT in Canine Mast Cell Tumor.
abstract: Canine cutaneous mast cell tumor (MCT) is the most common canine skin tumor and exhibits variable biologic behavior. Signaling through the KIT receptor tyrosine kinase promotes cellular proliferation and survival and has been shown to play a role in MCT progression. Despite investigations into numerous biomarkers and the proposal of several grading schemas, no single marker or grading system can accurately predict outcome in canine MCT. The first aim of this study was to develop an immunohistochemical assay to measure phosphorylated KIT (pKIT) to investigate its association with 2 commonly used grading systems and other established prognostic markers for canine MCT. Thirty-four archived MCTs were evaluated for expression of pKIT and Ki-67, KIT localization, mitotic count, mutations in exons 8 and 11 in c-kit, and grading by the Patnaik and 2-tier systems. Expression of pKIT was significantly ( P < .05) correlated with the 2-tier grading scheme and c-kit mutation. Correlation approached significance ( P = .06) with Mitotic Index (MI) and Ki-67. An additional aim was to determine whether pKIT labeling provides a pharmacodynamic marker for predicting response to the receptor tyrosine kinase inhibitor toceranib (TOC). MCTs from 4 of 7 patients demonstrated a partial response to TOC. pKIT expression was assessed by immunohistochemistry in biopsies obtained before and 6 hours after the patients were treated with TOC. Reduced pKIT expression after TOC treatment was demonstrated in 3 of the 4 patients with a partial response compared to 1 of the 3 nonresponders. Collectively, these results demonstrate that immunohistochemical detection of pKIT may be a clinically relevant assay to evaluate the activation status of the major oncogenic pathway in canine MCT.
authors.affiliation: 1 Cell and Molecular Biology, Colorado State University, Fort Collins, CO, USA.
authors.forename: C H C
authors.initials: CHC
authors.lastname: Halsey
authors.affiliation: 1 Cell and Molecular Biology, Colorado State University, Fort Collins, CO, USA.|2 Department of Clinical Sciences, College of Veterinary Medicine and Biosciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Thamm
authors.affiliation: 2 Department of Clinical Sciences, College of Veterinary Medicine and Biosciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Weishaar
authors.affiliation: 3 Department of Surgical & Radiological Sciences, College of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Burton
authors.affiliation: 2 Department of Clinical Sciences, College of Veterinary Medicine and Biosciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Charles
authors.affiliation: 1 Cell and Molecular Biology, Colorado State University, Fort Collins, CO, USA.|2 Department of Clinical Sciences, College of Veterinary Medicine and Biosciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Gustafson
authors.affiliation: 1 Cell and Molecular Biology, Colorado State University, Fort Collins, CO, USA.|4 Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biosciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Avery
authors.affiliation: 1 Cell and Molecular Biology, Colorado State University, Fort Collins, CO, USA.|2 Department of Clinical Sciences, College of Veterinary Medicine and Biosciences, Colorado State University, Fort Collins, CO, USA.|4 Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biosciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Ehrhart
mesh_terms: D000818:Animals; D015415:Biomarkers; D004283:Dog Diseases / Q000175:diagnosis / Q000473:pathology*; D004285:Dogs; D034701:Mastocytosis, Cutaneous / Q000175:diagnosis / Q000473:pathology / Q000662:veterinary*; D010766:Phosphorylation; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D019009:Proto-Oncogene Proteins c-kit
keywords: dog; immunohistochemistry; oncology; pharmaceutical; technology; toxicologic