Abstract
BackgroundThe epidermal growth factor receptors participate in the physiological processes such as regulation of morphogenesis, proliferation and cell migration, but when overexpressed or overactivated they may play an important role in neoplastic progression. Melanoma is the most aggressive skin neoplasm and is characterized by elevated invasion and low survival rates in both humans and dogs. In human melanomas the overexpression of EGFR, HER3 or HER4 is associated with poor prognosis. In canine melanomas the epidermal growth factor receptors expression has not been evaluated. Therefore, this study evaluated the expression of epidermal growth factor receptors by immunohistochemistry and investigated their relationship with morphological characteristics and proliferative indices in cutaneous and oral canine melanoma.ResultsIn cutaneous melanoma an increased proliferative index was associated with increased cytoplasmic HER4 and reduced EGFR and HER3 protein expression. In oral melanomas, membranous HER2 protein expression correlated with occurrence of emboli, but ERBB2 gene amplification wasn’t observed.ConclusionThus, our work evidenced the relationship between HER4 and the stimulus to cell proliferation in cutaneous melanomas, in addition to the relationship between HER2 and the occurrence of emboli in oral melanomas.
Highlights
The epidermal growth factor receptors participate in the physiological processes such as regulation of morphogenesis, proliferation and cell migration, but when overexpressed or overactivated they may play an important role in neoplastic progression
The epidermal growth factor receptors EGFR, HER2, HER3 and HER4 participate in the regulation of cell morphogenesis, proliferation, migration and adhesion [1]
Due to the high aggressiveness of canine melanoma and the scarcity of information of association with epidermal growth factor receptors and canine melanoma progression, the aims of the present study were to characterize the expression of EGFR, HER2, HER3 and HER4 in skin and oral canine melanoma and to determine their relationship with the histopathological characteristics and proliferative indices of these tumors
Summary
The epidermal growth factor receptors participate in the physiological processes such as regulation of morphogenesis, proliferation and cell migration, but when overexpressed or overactivated they may play an important role in neoplastic progression. In canine melanomas the epidermal growth factor receptors expression has not been evaluated. The epidermal growth factor receptors EGFR, HER2, HER3 and HER4 participate in the regulation of cell morphogenesis, proliferation, migration and adhesion [1]. These receptors are transmembrane proteins composed of an extracellular epidermal growth factor (EGF)-binding domain, a transmembrane domain and a cytoplasmic domain with tyrosine kinase activity [2]. In vitro and in silico studies in human melanoma cell lines and experimental murine melanoma models found that epidermal growth factor receptors are promising therapeutic targets [11, 12]
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