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Comparative Medicine and Integrative Biology Program (JDW, VYG, JBK, MK); Department of Pathobiology and Diagnostic Investigation (JDW, MK); Department of Small Animal Clinical Sciences (VYG); Department of Microbiology and Molecular Genetics (VYG); Center for Comparative Epidemiology (JBK, RAM), College of Veterinary Medicine, Michigan State University
Canine cutaneous mast cell tumor (MCT) is a common neoplastic disease in dogs. Due to the prevalence of canine MCTs and the variable biologic behavior of this disease, accurate prognostication and a thorough understanding of MCT biology are critical for the treatment of this disease. The goals of this study were to evaluate and compare the utility of the proliferation markers Ki67, proliferating cell nuclear antigen (PCNA), and argyrophilic nucleolar organizing region (AgNOR) as independent prognostic markers for canine MCTs and to evaluate the use of these markers in combination, as each marker assesses different aspects of cellular proliferation. An additional goal of this study was to evaluate the associations between cellular proliferation and c-KIT mutations and between cellular proliferation and aberrant KIT protein localization in canine MCTs. Fifty-six MCTs treated with surgical excision alone were included in this study. Each MCT was evaluated for Ki67 expression, PCNA expression, and KIT protein localization using immunohistochemistry; for AgNOR counts using histochemical staining; and for the presence of internal tandem duplication c-KIT mutations using polymerase chain reaction amplification. In this study, increased Ki67 and AgNOR counts were both associated with significantly decreased survival. On the basis of these results, we recommend that the evaluation of cellular proliferation, including evaluations of both Ki67 expression and AgNORs, should be routinely used in the prognostication of canine MCTs. Additionally, the results of this study show that MCTs with aberrant KIT protein localization or internal tandem duplication c-KIT mutations are associated with increased cellular proliferation, further suggesting a role for c-KIT in the progression of canine MCTs.
Key words: AgNOR; canine; c-KIT; Ki67; mast cell tumors; PCNA; prognostic markers; proliferation.
Request reprints from Dr. M Kiupel, Diagnostic Center for Population and Animal Health, Michigan State University, 4125 Beaumont Road, Room 152A, Lansing, MI 48910 (USA). E-mail: kiupel{at}dcpah.msu.edu
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