Tumour development is dependent upon the formation of an adequate blood supply through angiogenesis. Vascular endothelial growth factor (VEGF) is one of the most potent and specific pro-angiogenic factors associated with tumour development. Vascular endothelial growth factor is elevated in dogs with a variety of neoplastic tumours and has been linked to an increased risk for metastasis and a poorer prognosis in several tumours. Spirocerca lupi (S. lupi) is a nematode of canids which infests the oesophagus where it forms a nodule. The oesophageal nodule can develop into a neoplastic tumour namely osteosarcoma, fibrosarcoma or anaplastic sarcoma. The pathogenesis of the neoplastic transformation is poorly understood. Diagnosis of neoplastic transformation can be challenging and is based on endoscopy-guided biopsies which are invasive, expensive and may yield non diagnostic samples. The aim of this prospective study was to determine if serum and plasma VEGF levels could be used to distinguish between neoplastic and non-neoplastic spirocercosis. Twenty four dogs were enrolled in the study, 9 with non-neoplastic, 9 with neoplastic spirocercosis, and 6 control dogs. Plasma and serum samples for VEGF analysis were collected at diagnosis. Measurement of VEGF was done using a canine VEGF Quantikine ELISA kit. Statistical analysis to compare the means of the VEGF concentrations between the groups was performed using the Kruskal-Wallis followed by the Dunn’s test. Significance was set at p<0.05 The median plasma VEGF concentration of the dogs with neoplastic spirocercosis 629pg/ml (range 282 – 2366) was higher than the median plasma VEGF concentrations of both the non-neoplastic 0pg/ml (range 0 – 716) and controls 0pg/ml (range 0 – 0) (p<0.001). The median serum VEGF concentration of the neoplastic dogs 69pg/ml (range 0 – 212) was higher than the serum VEGF concentrations in the non-neoplastic 0pg/ml (range 0 – 44.13) and control 0pg/ml (range 0 – 39.4) (p=0.001). Plasma VEGF at a cut off value of 250pg/ml was determined to have a sensitivity of 100%, specificity of 77.8%, a PPV of 81.8% and a NPV of 100% for determining neoplastic transformation. Serum VEGF at a cut off value of 25pg/ml was determined to have a sensitivity of 88.9%, specificity of 100%, a PPV of 100% and a NPV of 90% for determining neoplastic transformation. Both plasma and serum VEGF concentrations can be used to differentiate between non-neoplastic and neoplastic spirocercosis. Plasma VEGF concentrations were higher than serum VEGF concentrations, contrary to what is reported in literature. Both plasma and serum VEGF concentrations can, therefore, potentially be used for diagnosis of neoplastic vs. non-neoplastic cases in canine spirocercosis. There is a need to perform more studies to determine cut-off concentrations that would maximize the sensitivity and specificity for determining neoplastic transformation in canine spirocercosis as well as to determine the role of VEGF in the pathogenesis of the neoplastic transformation. Copyright
Dissertation (MMedVet)--University of Pretoria, 2012.