CD117 immunoexpression in canine mast cell tumours: correlations with pathological variables and proliferation markers

Abstract

BackgroundCutaneous mast cell tumours are one of the most common neoplasms in dogs and show a highly variable biologic behaviour. Several prognosis tools have been proposed for canine mast cell tumours, including histological grading and cell proliferation markers. CD117 is a receptor tyrosine kinase thought to play a key role in human and canine mast cell neoplasms. Normal (membrane-associated) and aberrant (cytoplasmic, focal or diffuse) CD117 immunoexpression patterns have been identified in canine mast cell tumours. Cytoplasmic CD117 expression has been found to correlate with higher histological grade and with a worsened post-surgical prognosis. This study addresses the role of CD117 in canine mast cell tumours by studying the correlations between CD117 immunoexpression patterns, two proliferation markers (Ki67 and AgNORs) histological grade, and several other pathological variables.ResultsHighly significant (p < 0,001) correlations were found between CD117 immunostaining patterns and histological grade, cell proliferation markers (Ki67, AgNORs) and tumoral necrosis. Highly significant (p < 0,001) correlations were also established between the two cellular proliferation markers and histological grade, tumour necrosis and epidermal ulceration. A significant correlation (p = 0.035) was observed between CD117 expression patterns and epidermal ulceration. No differences were observed between focal and diffuse cytoplasmic CD117 staining patterns concerning any of the variables studied.ConclusionThese findings highlight the key role of CD117 in the biopathology of canine MCTs and confirm the relationship between aberrant CD117 expression and increased cell proliferation and higher histological grade. Further studies are needed to unravel the cellular mechanisms underlying focal and diffuse cytoplasmic CD117 staining patterns, and their respective biopathologic relevance.

Prognostic Value of Histologic and Immunohistochemical Features in Feline Cutaneous Mast Cell Tumors

“…7,20,38 C-kit mutations in dogs are mostly associated with aberrant cytoplasmic KIT expression by neoplastic mast cells, 35,39 and dogs with tumors that have these mutations or KIT overexpression have a worse prognosis and are considered good candidates for treatment with kinase inhibitors. 9,17,21,31,35,39 Feline MCT is suspected to have similar carcinogenetic mechanisms, and c-kit mutation in the extracellular ligand-binding domain (exon 8) has been recently reported in a cat, which responded to treatment with the tyrosine kinase inhibitor imatinib mesylate. 14 KIT immunopositivity has been demonstrated in feline MCTs; 27,33 in one report, cytoplasmic expression of KIT was detected in 18 of 27 cutaneous MCTs (67%), without correlation with the histotype.…”

“…9 Additionally, CD117 immunoreactivity was scored (KIT immunoreactivity score [KIT IS]) as the product of the percentage of positive cells (1, 10%; 2, 11 to 30%; 3, 31 to 60%; or 4, > 60%) and the intensity of labeling (1, low; 2, moderate; 3, high).…”

c-KIT messenger RNA and protein expression and mutations in canine cutaneous mast cell tumors

“…4,11,39 Thus, new proposals for more accurate prediction of the biological behavior of canine cutaneous and subcutaneous MCTs have been formulated. 9,35 In the present study, the Patnaik and 2-tier histological systems were used to classify MCT cases, and both systems were compared with post-surgical clinical prognosis.…”

Nuclear Morphometry in Cytopathology: A Prognostic Indicator for Canine Cutaneous Mast Cell Tumors

“…The best results have been achieved with proliferation markers 1,3,18,31,33 and KIT expression patterns. 10,15,19,20,30,36,37 Among the methods proposed to complement histomorphologic grading, computerized morphology is worthy of notice. This procedure has already proved useful in several types of human cancer, 6,9,11,13 and its application in veterinary medicine has been increasing.…”