Investigation of the Theragnostic Role of KIT Expression for the Treatment of Canine Mast Cell Tumors with Tyrosine Kinase Inhibitors


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Article

by

Davide De Biase

1,†,

Marcello De Leo

2,†,

Giuseppe Piegari

2,*,†,

Ilaria d’Aquino

2,

Evaristo Di Napoli

2,

Carmela Mercogliano

2,

Alfonso Calabria

2,

Agata Pula

2,

Luigi Navas

2,

Valeria Russo

2 and

Orlando Paciello

2

1

Department of Pharmacy, University of Salerno, 84084 Fisciano, Italy

2

Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80138 Napoli, Italy

*

Author to whom correspondence should be addressed.

These authors contributed equally to this work.

Submission received: 19 August 2024
/
Revised: 29 September 2024
/
Accepted: 8 October 2024
/
Published: 10 October 2024

Simple Summary

Canine mast cell tumors (MCTs) are a neoplasm frequently diagnosed in dogs that have a very variable aggressive behavior. The aim of our research was to assess the potential role of KIT in canine mast cell tumors in term of response to therapy by investigating the association between KIT expression patterns, the cumulative survival and the progression-free survival in dogs treated with tyrosine kinase inhibitors postoperatively. Dogs that underwent surgery alone were used as a control population. A log-rank test was used to check the differences between the curves, showing that tumors with KIT staining pattern 3 were significantly associated with decreased CS compared to tumors with KIT patterns 2 and 1. Our data suggest that the anomalous expression of KIT is negatively associated with the efficacy of tyrosine kinase inhibitors, thus providing a meaningful prognostic information about the treatment outcome.

Abstract

Several reports have indicated that canine MCTs express a mutated form of a tyrosine kinase receptor, namely KIT, that is involved in abnormal mast cell growth and differentiation. Currently, the post-surgical prognosis for MCTs is related to three different KIT immunohistochemical expression patterns. However, to our knowledge, there are few studies specifically exploring the efficacy of treatment with tyrosine kinase inhibitors related to KIT staining pattern. The purpose of this study was to investigate the potential theragnostic role of KIT expression patterns by studying their correlation to the overall survival and progression-free survival in dogs treated with only tyrosine kinase inhibitors immediately after surgery. We selected 66 cases of canine cutaneous MCTs with complete clinical background. A statistical analysis was performed to assess the overall survival status. Our data suggest an important role of KIT in the etiopathogenesis of canine MCTs and indicate that the anomalous cytoplasmatic distribution of KIT is potentially related to a lower efficacy of tyrosine kinase inhibitors, thus providing a significant prognostic information about the treatment outcome.

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