Introduction

We established a prognostic panel for canine cutaneous mast cell tumors (MCTs) based on a 2-tier grading system, the Ki67 index and the combined Ki67/AgNOR index and immunohistochemical expression patterns of KIT. We previously demonstrated that the presence of exon 11 mutations in c-Kit was associated with a poor prognosis, while the role of mutations in exon 8 of c-Kit has not been investigated.

Objective

The goal of this retrospective study was to investigate the prognostic significance of exon 8 and 11 mutations in MCTs.

Methods

KIT pattern, Ki67 index, and combined Ki67/AgNOR index were determined for 69 MCTs with exon 8 mutations, 105 MCTs with exon 11 mutations, and 50 MCTs with no mutation in either exon. Multivariate statistical analysis was performed to determine correlations between different mutations, other parameters measured, as well as overall survival times.

Results

While aberrant KIT expression, a high Ki67 index, a high combined Ki67/AgNOR index, and high tumor grade were significantly associated with exon 11 mutations, there was no significant association of the investigated parameters with mutations in exon 8 or no mutations. Dogs with MCTs with exon 11 mutations had significantly shorter disease-free survival times and overall survival times than dogs with MCTs with mutations in exon 8 that had similar survival times as dogs with MCTs with no mutation.

Conclusions

Mutations in exon 11 of c-Kit predict a high risk of systemic disease, while mutations in exon 8 are most commonly found in MCTs that only cause local disease.