Expression and Prognostic Evaluation of the Receptor Tyrosine Kinase MET in Canine Malignant Melanoma

SIMPLE SUMMARY: Melanoma is a cancer of cells that produce melanin pigment, and it can develop in dogs as well as in humans. Canine melanoma has a high risk of metastasis and is resistant to systemic chemotherapy. Therefore, alternative effective systemic treatment is urgently needed. Abnormal expression and activation of the receptor tyrosine kinase MET is reported in many human cancers, including melanoma. However, the role of MET in canine melanoma is unknown. The purpose of this study is to confirm MET expression in canine melanomas and determine if the levels of expression correlate with prognosis. A review of 30 canine melanoma cases confirmed mild MET expression in more than 50% of these samples. While the levels of MET expression were not significantly associated with key histologic features or survival, a difference in time to metastasis to lymph nodes versus other organs was noted. This may suggest a role for MET expression in the pattern of metastasis, which may in turn help with patient stratification and treatment recommendation. ABSTRACT: The overexpression and activation of the MET receptor tyrosine kinase has been identified in many human malignancies, but its role in canine cancer has only been minimally investigated. In this study we evaluated the expression of MET in two canine malignant melanoma (CMM) cell lines as well as in 30 CMM tissue samples that were collected from the clinical service at our institution. We were able to confirm the expression of the MET protein in both melanoma cell lines, and we demonstrated MET activation by its ligand, HGF, through phosphorylation, in Western blot analysis. We were also able to demonstrate, by immunohistochemistry, the expression of MET in 63% of the tumor tissue samples analyzed, with the majority demonstrating a relatively low expression profile. We then evaluated the association of MET expression scores with histologic parameters, metastasis, and survival. While statistically significant associations were not found across these parameters, an inverse relationship between MET expression levels and time to lymph node versus distant metastasis was suggested in our cohort. These findings may require assessment in a larger group of specimens to further evaluate the role of MET expression in the homing of metastasis in lymph nodes versus that in distant organs.