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Cell proliferation and expression of connexins differ in melanotic and amelanotic canine oral melanomas
Authors:Tarso Felipe Teixeira  Luciana Boffoni Gentile  Tereza Cristina da Silva  Gregory Mennecier  Lucas Martins Chaible  Bruno Cogliati  Marco Antonio Leon Roman  Marco Antonio Gioso  Maria Lucia Zaidan Dagli
Institution:1. Laboratory of Experimental and Comparative Oncology, Department of Pathology, School of Veterinary Medicine and Animal Science, University of S?o Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, CEP 05508-900, S?o Paulo, SP, Brazil
2. Laboratory of Comparative Dentistry, Department of Surgery, School of Veterinary Medicine and Animal Science, University of S?o Paulo, S?o Paulo, SP, Brazil
Abstract:Melanoma is a malignant neoplasm occurring in several animal species, and is the most frequently found tumor in the oral cavity in dogs. Melanomas are classified into two types: melanotic and amelanotic. Prior research suggests that human amelanotic melanomas are more aggressive than their melanotic counterparts. This study evaluates the behavior of canine melanotic and amelanotic oral cavity melanomas and quantifies cell proliferation and the expression of connexins. Twenty-five melanomas (16 melanotic and 9 amelanotic) were collected from dogs during clinical procedures at the Veterinary Hospital of the School of Veterinary Medicine and Animal Science of the University of São Paulo, Brazil. After diagnosis, dogs were followed until death or euthanasia. Histopathology confirmed the gross melanotic or amelanotic characteristics and tumors were classified according to the WHO. HMB45 or Melan A immunostainings were performed to confirm the diagnosis of amelanotic melanomas. Cell proliferation was quantified both by counting mitotic figures and PCNA positive nuclei. Expressions of connexins 26 and 43 were evaluated by immunohistochemistry, qRT-PCR and Western blot. Dogs bearing amelanotic melanomas presented a shorter lifespan in comparison to those with melanotic melanomas. Cell proliferation was significantly higher in amelanotic melanomas. Expressions of Connexins 26 and 43 were significantly reduced in amelanotic melanomas. The results presented here suggest that oral cavity melanotic and amelanotic melanomas differ regarding their behavior, cell proliferation and connexin expression in dogs, indicating a higher aggressiveness of amelanotic variants.
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