| Canine cutaneous mast cell tumors (MCTs) are one of the most common neoplastic diseases in dogs, and have an extremely variable biologic behavior ranging from a benign, solitary mass to a potentially fatal metastatic disease. Due to the high prevalence of canine MCTs, their variable biologic behavior, the physical, emotional, and financial costs associated with various treatment protocols, accurate prognostication of canine MCTs is critical in order to identify patients that will benefit most from adjunct radiation and chemotherapy. Currently, histologic grading is the major prognostic and therapeutic determinant for canine MCTs as several studies have shown a significant association between histologic grades and survival. However, the marked degree of inter-observer variation associated with histologic grading, and the predominance of intermediate grade MCTs, has led many to question the relevance of the current system. An additional concern with the treatment and prognostication of canine cutaneous MCTs is the current lack of knowledge in terms of the biology of these tumors. Therefore, in light of our current knowledge gap and the need for improved prognostication of canine MCTs, the goals of this dissertation were: (1) to identify novel markers and characterize previously described markers for the prognostication of canine MCTs; (2) to characterize the role of the c-KIT proto-oncogene in the pathogenesis of canine cutaneous MCTs. The studies described in this dissertation elucidate the utility of KIT staining patterns, c-KIT mutations, and proliferation markers such as Ki67 and AgNORs in the prognostication of canine cutaneous MCTs, and demonstrate the inadequacy of tumor depth, tumor location, tryptase staining patterns, and PCNA immunostaining for prognostication. Additionally, the studies described in this dissertation clarify the role of the c-KIT proto-oncogene in the pathogenesis of canine MCTs, demonstrating c-KIT's importance in the progression of this disease. In summary, the results of these studies strengthen the current body of knowledge of canine MCTs both in terms of diagnostics and basic biology, and these results should serve as building blocks for further hypotheses and future studies. |
