Expression of vascular endothelial growth factor (VEGF) in equine sarcoid

Abstract

BackgroundSarcoids are the mostcommon skin tumors in horses, characterized by rare regression, invasiveness and high recurrence following surgical intervention and Delta Papillomaviruses are widely recognized as the causative agents of the disease. In order to gain new insights into equine sarcoid development, we have evaluated, in 25 equine sarcoids, by immunohistochemistry and western blotting analysis, the expression levels of VEGF, Ki67 and bcl-2. Moreover, we have measured microvessel density and specific vessel parameters.ResultsAll sarcoid samples showed a strong and finely granular cytoplasmatic staining for VEGF in the majority (90%) of keratinocytes, sarcoid fibroblasts and endothelial cells. Numerous small blood vessels, immunostained with Von Willebrand factor, often appeared irregular in shape and without a distinct lumen, with mean values of microvessel area and perimeter lower than normal. Moreover, in all sarcoid samples, Ki67 immunoreactivity was moderately positive in 5–10% of dermal sarcoid fibroblasts, while Bcl2 immunoreactivity was detected in 52% of the sarcoid samples, with a weak staining in 20–50% of dermal sarcoid fibroblasts. Biochemical analysis was consistent with immunohistochemical results.ConclusionsThis study has provided evidence that in equine sarcoid: VEGF was strongly expressed; the increased number of vessels was not associated with their complete maturation, probably leading to a hypoxic condition, which could increase VEGF synthesis; the levels of sarcoid fibroblasts proliferation were very low. Concluding, VEGF may have a role in equine sarcoid development, not only through the increase of angiogenesis, but also through the control of sarcoid fibroblast activity.

Evaluation of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) in Equine Sarcoid: An Immunohistochemical and Biochemical Study

“…The rank correlation analysis showed that the percentage of HIF-1α positive cells was positively correlated with the percentage of VEGF positive cells found during a previous study by our group (r = 0.60 p < 0.01) [27].…”

“…The examined sarcoids (n = 35) showed the classic histological features of the lesion: epidermal hyperplasia with rete pegs; hyperkeratosis; proliferation of neoplastic fibroblast in the dermal layer, oriented in a 'picket fence' perpendicular to the basilar epidermal layer; exuberant extracellular matrix; presence of many small vessels irregular in shape [26,27].…”

“…The protein E5, in synergy with E7, induces DNA damages and genomic instability [20][21][22][23], leading to the cell transformation and to subsequent development of cancer [12]. The principal mechanisms whereby the BPV major oncogene E5 induces malignant transformation, involve the activation of platelet-derived growth factor βeta-receptor (PDGFβ-r) [24], the immune evasion [11], the resistance to apoptosis [25], the upregulation of matrix metalloproteinase (MMPs) with consequent alteration of extracellular matrix (ECM) turnover [26], and the increase of angiogenesis [27]. Angiogenesis, the development of new vessels, is necessary for neoplastic invasion, growth, and metastasis, and has a crucial role in the development and progression of numerous human and animal cancers [28][29][30][31][32][33][34][35][36][37].…”

“…We have recently shown an overexpression of VEGF and abnormal vessel structures [27] in equine sarcoids, which could cause a hypoxic condition, leading to an upregulation of HIF-1α.…”

“…Since the specific function of HIF-1α in sarcoid pathogenesis has not been investigated, so far, we analyzed the expression of HIF-1α in 35 BPV positive equine sarcoids and explored the relationship with VEGF expression reported in our previous study [27].…”