Expression of Phosphorylated KIT in Canine Mast Cell Tumor

C. H.C. Halsey, D. H. Thamm, K. M. Weishaar, Jenna H Burton, J. B. Charles, D. L. Gustafson, A. C. Avery, E. J. Ehrhart

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)387-394
Number of pages8
JournalVeterinary Pathology
Volume54
Issue number3
DOIs
StatePublished - May 1 2017

Fingerprint

mast cells
Mast Cells
Canidae
neoplasms
dogs
Neoplasms
Receptor Protein-Tyrosine Kinases
tyrosine
phosphotransferases (kinases)
mutation
receptors
assays
pharmacology
Skin
Mutation
Mitotic Index
exons
immunohistochemistry
biopsy
biomarkers

Keywords

  • dog
  • immunohistochemistry
  • oncology
  • pharmaceutical
  • technology
  • toxicologic

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Halsey, C. H. C., Thamm, D. H., Weishaar, K. M., Burton, J. H., Charles, J. B., Gustafson, D. L., ... Ehrhart, E. J. (2017). Expression of Phosphorylated KIT in Canine Mast Cell Tumor. Veterinary Pathology, 54(3), 387-394. https://doi.org/10.1177/0300985816688943

Expression of Phosphorylated KIT in Canine Mast Cell Tumor. / Halsey, C. H.C.; Thamm, D. H.; Weishaar, K. M.; Burton, Jenna H; Charles, J. B.; Gustafson, D. L.; Avery, A. C.; Ehrhart, E. J.

In: Veterinary Pathology, Vol. 54, No. 3, 01.05.2017, p. 387-394.

Research output: Contribution to journalArticle

Halsey, CHC, Thamm, DH, Weishaar, KM, Burton, JH, Charles, JB, Gustafson, DL, Avery, AC & Ehrhart, EJ 2017, 'Expression of Phosphorylated KIT in Canine Mast Cell Tumor', Veterinary Pathology, vol. 54, no. 3, pp. 387-394. https://doi.org/10.1177/0300985816688943
Halsey CHC, Thamm DH, Weishaar KM, Burton JH, Charles JB, Gustafson DL et al. Expression of Phosphorylated KIT in Canine Mast Cell Tumor. Veterinary Pathology. 2017 May 1;54(3):387-394. https://doi.org/10.1177/0300985816688943
Halsey, C. H.C. ; Thamm, D. H. ; Weishaar, K. M. ; Burton, Jenna H ; Charles, J. B. ; Gustafson, D. L. ; Avery, A. C. ; Ehrhart, E. J. / Expression of Phosphorylated KIT in Canine Mast Cell Tumor. In: Veterinary Pathology. 2017 ; Vol. 54, No. 3. pp. 387-394.
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