Abstract
Backgroundc-KIT expression has been related to bone metastasis in human prostate cancer, but whether c-KIT expression can be similarly classified in canine prostatic tissue is unknown. This study assessed c-KIT and Ki67 expression in canine prostate cancer (PC). c-KIT gene and protein expression and Ki67 expression were evaluated in forty-four canine prostatic tissues by immunohistochemistry, RT-qPCR and western blot. Additionally, we have investigated c-KIT protein expression by immunoblotting in two primary canine prostate cancer cell lines.ResultsEleven normal prostates, 12 proliferative inflammatory atrophy (PIA) prostates, 18 PC, 3 metastatic lesions and two prostate cancer cell cultures (PC1 and PC2) were analysed. The prostatic tissue exhibited varying degrees of membranous, cytoplasmic or membranous/cytoplasmic c-KIT staining. Four normal prostates, 4 PIA and 5 prostatic carcinomas showed positive c-KIT expression. No c-KIT immunoexpression was observed in metastases. Canine prostate cancer and PIA samples contained a higher number of Ki67-positive cells compared to normal samples. The median relative quantification (RQ) for c-KIT expression in normal, PIA and prostate cancer and metastatic samples were 0.6 (0.1-2.5), 0.7 (0.09-2.1), 0.7 (0.09-5.1) and 0.1 (0.07-0.6), respectively. A positive correlation between the number of Ki67-positive cells and c-KIT transcript levels was observed in prostate cancer samples. In the cell line, PC1 was negative for c-KIT protein expression, while PC2 was weakly positive.ConclusionThe present study identified a strong correlation between c-KIT expression and proliferative index, suggesting that c-KIT may influence cell proliferation. Therefore, c-KIT heterogeneous protein expression among the samples (five positive and thirteen negative prostate cancer samples) indicates a personalized approach for canine prostate cancer.
Highlights
Prostate cancer (PC) in dogs is associated with aggressive tumour behaviour, high metastatic rate and poor prognosis [1]
Clinical data All clinical information about breed, age and metastatic history from the fourteen dogs with prostate cancer (PC) are shown in Additional file 1: Table S1
There were no significant differences between survival time and c-KIT or Ki67 expression
Summary
Prostate cancer (PC) in dogs is associated with aggressive tumour behaviour, high metastatic rate and poor prognosis [1]. The proto-oncogene c-KIT belongs to the class III receptor tyrosine kinase family, and its ligand (stem cell factor protein) represents the mast cell growth factor in humans and dogs [15, 16]. In xenografts models of human PC with low c-KIT expression, the receptor is upregulated during cancer progression through production. Osteoclasts produce stem cell factor, stimulating PC cells to increase c-KIT expression and, subsequently, their migration from the primary tumour to bones [14]. Inhibition of c-KIT using lentiviral short hairpin RNA in human PC cell lines reduced tumour growth and increased the incidence of metastasis, suggesting a key role for c-KIT in intraosseous tumour growth in xenografts model [17]
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