RESUMEN
The c-kit receptor is responsible for transmission of promigration signals to melanocytes; its downregulation may be involved in malignant progression of human melanocytic neoplasms. Expression of this receptor has not been examined in normal or neoplastic melanocytes from dogs. In this study, 14 benign dermal and 61 malignant mucosal melanocytic tumors were examined for c-kit (KIT) expression. Sites of the mucosal melanomas were gingiva (not further specified; n = 30), buccal gingiva (n = 6), soft palate (n = 4), hard palate (n = 5), tongue (n = 7), lip (n = 6), and conjunctiva (n = 3). Melan A was expressed in all 14 dermal melanocytomas and in 59 of 61 (96.7%) tumors from oral or conjunctival mucosa, confirming melanocytic origin. C-kit receptor expression was strong and diffuse throughout the cytoplasm in all 14 dermal melanocytomas and was identified in basilar mucosal melanocytes over submucosal neoplasms (27 of 61, 44.3%), junctional (neoplastic) melanocytes (17 of 61, 27.9%), and, less commonly, neoplastic melanocytes of the subepithelial tumors (6 of 61, 9.8%). KIT expression anywhere within the resected melanomas correlated with significantly longer survival. These results suggest that c-kit receptor expression may be altered in canine melanomas and may have potential as a prognostic indicator for mucosal melanomas.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Conjuntiva/veterinaria , Enfermedades de los Perros/metabolismo , Melanoma/veterinaria , Neoplasias de la Boca/veterinaria , Proteínas Proto-Oncogénicas c-kit/metabolismo , Animales , Neoplasias de la Conjuntiva/metabolismo , Neoplasias de la Conjuntiva/patología , Progresión de la Enfermedad , Enfermedades de los Perros/mortalidad , Enfermedades de los Perros/patología , Perros , Femenino , Regulación Neoplásica de la Expresión Génica , Inmunohistoquímica/veterinaria , Antígeno MART-1/metabolismo , Masculino , Melanocitos/metabolismo , Melanocitos/patología , Melanoma/metabolismo , Melanoma/patología , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Pronóstico , Proteínas Tirosina Quinasas Receptoras/metabolismo , Proteínas S100/metabolismo , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/veterinaria , Análisis de SupervivenciaRESUMEN
Gliomas are among the most common primary neural tumours of dogs. Cyclooxygenase-2 (COX-2) and c-kit overexpression are associated with increased aggressiveness of gliomas and decreased survival in human beings. COX-2 is the inducible form of cyclooxygenase, which catalyzes prostaglandin formation and may increase tumour proliferation and angiogenesis. C-kit is a tyrosine kinase receptor involved in normal cell physiology; c-kit is upregulated in some canine tumours. In this retrospective study, 20 canine gliomas were identified: 11 (55%) oligodendrogliomas, including 1 anaplastic variant; 1 (5%) oligoastrocytoma; and 8 (40%) astrocytomas, of which 2 were glioblastoma multiforme. None of the gliomas expressed COX-2. None of the gliomas were immunoreactive for c-kit, although all three high-grade tumours had intramural vascular expression. Consequently, COX-2 inhibitors would likely be ineffective against canine gliomas. C-kit inhibitors may have an anti-angiogenic effect in high-grade gliomas, but would likely be ineffective in low- and medium-grade tumours.