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Prognostic value of Vascular Endothelial Growth Factor and Hypoxia-Inducible Factor 1a in canine malignant mammary tumors


Mammary tumors are the most common type of tumor in dogs, with approximately half of these tumors are malignant. Hypoxia, characterized by oxygen levels below normal, is a known adverse factor to cancer treatment. The hypoxia-inducible factor 1a (HIF -1a) is a central regulator of pathophysiological response of mammalian cells to low oxygen levels; it activates the transcription of the vascular endothelial growth factor (VEGF), which in turn promotes angiogenesis through its ability to stimulate growth, migration and invasion of endothelial cells to form new blood vessels, contributing to tumor progression. In this study, we evaluated the serum concentration and the gene expression of VEGF and HIF-1a linking them with clinicopathological parameters and survival of dogs with mammary tumors in order to infer the possible prognostic value of these factors. We collected blood and tumor fragments of 24 bitches with malignant mammary tumors (study group) and 26 non-affect female dogs (control group) to verify the gene expression of VEGF and HIF-1a by Quantitative Real Time PCR (qPCR) and the serum levels by ELISA (Enzyme-linked immunosorbent). The results showed high serum levels of VEGF in the study group and its correlation between abundant vascularization, lymph node involvement, metastasis, death rate and low survival (p<0.05). The serum percentage of HIF-1a in bitches with mammary neoplasia was lower than in the control group and higher in female dogs with tumor metastasis and history of tumor recurrent (p<0.05). Regarding gene expression, there was a gene overexpression of VEGFA in female dogs with poor outcome, in contrast to the gene underexpression of HIF-1A. Taken together, these results suggest that VEGF plays an important role in tumor progression and can be used as a potential prognostic marker in clinical practice, being useful in predicting tumor progression in dogs with mammary neoplasia. (AU)

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