Study of c-kit immunoexpression in canine cutaneous melanocytic tumors

Abstract

Melanocytic tumors occur as much in humans as in dogs and are frequently associated with receptor tyrosine kinase dysregulation. The transmembrane c-kit protein is a receptor tyrosine kinase that is crucial in melanocytic homeostasis and, when mutated, is associated with tumor development in those cells. In human studies, its expression is generally detected in melanocytomas and primary malignant melanomas, being lost with tumor progression and metastasis. In this study, we aimed to analyze c-kit expression in canine cutaneous melanocytic tumors and its association with tumor behavior, in order to investigate the dog’s potential in comparative pathology and c-kit’s potential in the diagnosis of these tumors. The expression of c-kit was evaluated immunohistochemically in 39 canine cutaneous melanocytic tumors and scored in terms of the labeling location, extension, and intensity. The labeling location was essentially cytoplasmic, and the labeling extension and intensity were generally higher in melanocytomas (83.3% diffuse-labeled cells) than those in malignant melanomas (22.2% negative-labeled cells). The differences found in the labeling extension were statistically significant (P<0.001). There was no association between c-kit immunoexpression in malignant melanomas and the clinicopathological criteria, except between the labeling intensity and the degree of intralesional pigmentation (P=0.048). Our results for labeling extension are in agreement with similar human studies, reinforcing the dog’s potential as a model organism for investigation in this type of cancer. In addition, the loss of c-kit expression in malignant melanomas might be a criterion of tumor aggressiveness, indicating that this receptor may be useful in the diagnosis of these tumors.