KIT receptor tyrosine kinase dysregulation in feline cutaneous mast cell tumour

Introduction Feline cutaneous mast cell tumours (cMCTs) are characterized by a variable biologic behaviour. Development of multiple cutaneous nodules and concurrent visceral involvement, along with inconsistency of conventional prognostic aids, justify present uncertainty in differentiating benign from malignant forms. c-kit proto-oncogene activating mutations have been reported in 68% of feline MCTs, however their prognostic relevance has not been determined. This is a prospective study performed on feline cMCTs with variable clinical presentation to assess whether KIT immunohistochemical overexpression can be regarded as indicative of c-kit mutations, and evaluate their relationship with disease progression. Materials and Methods Cats with a histological diagnosis of cMCT in the absence of visceral involvement were enrolled. Patients underwent surgery and were followed for at least 6 months. KIT/CD117 immunohistochemistry and c-kit mutation analysis (exons 8,9,11) were performed on tumour samples and correlated with DFI and OS. Results Twenty-one cats with 11 solitary, 4 multiple, and 6 disseminated cMCTs were included. Determinations were performed on 28 tumour samples. KIT cytoplasmic expression was observed in 20 tumours, showing a shorter DFI (P=0.013) and OS (P=0.04). c-kit encoding mutations were detected in 58% of cases (exon 8, 12%; exon 9, 46%; exon 11, 4%), but they were not directly correlated with clinical behaviour. Conclusion c-kit mutations occur frequently in feline cMCT, and their incidence is higher among tumours with a CD117 overexpression, but their prognostic relevance needs to be assessed in a larger series. Multiple nodules from any one cat did not harbour the same mutations, suggesting that they may represent separate events