Expression and prognostic significance of vascular endothelial growth factor‐A (VEGF‐A) and its receptor in canine prostate cancer. Issue 14 (28th July 2021)

• Record Type: Journal Article
• Authors: Leis‐Filho, Antonio Fernando; Lainetti, Patricia deFaria; Kobayashi, Priscila Emiko; Palmieri, Chiara; Amorim, Renée Laufer; Fonseca‐Alves, Carlos Eduardo
• Is Part Of: Prostate. Volume 81:Issue 14(2021)
• Page Start: 1021
• Page End: 1031
• Publication Date: 2021-07-28
• Subjects: angiogenesis -- cancer -- dog -- VEGF‐A -- VEGFR‐2; Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.24199
• Languages: English
• ISSNs: 0270-4137

Abstract

Abstract: Background: Vascular endothelial growth factor‐A (VEGF‐A) and its receptor, VEGF receptor‐2 (VEGFR‐2), represent a complex family of angiogenic molecules consisting of different ligands and receptors. Due to the importance of VEGF‐A/VEGFR‐2 signaling in tumor proliferation and angiogenesis, this study aimed to evaluate the protein and gene expression levels of VEGF‐A and VEGFR‐2 in canine prostate cancer (PC). Methods: We analyzed VEGF‐A and VEGFR‐2 expression in 87 PC samples by immunohistochemistry and quantitative‐polymerase chain reaction. PC samples were graded according to the Gleason score and the immunohistochemical staining for VEGF‐A and VEGFR‐2 was quantified using a selected threshold from the ImageJ Software. Microvascular density was assessed by cluster of differentiation 31 staining and counting the number of positive vessels. Additionally, the homology of VEGF‐A and VEGFR‐2 between humans and dogs was assessed, followed by the construction of a protein structure homology model to compare the tertiary structures of these proteins in both species. Results: Negative to weakly positive expression levels of VEGF‐A and VEGFR‐2 were observed in the epithelial cells of the normal prostate (NP) and prostatic hyperplasia samples. In contrast, the canine proliferative atrophy and PC samples exhibited higher VEGF‐A ( p < .0001) and VEGFR‐2 ( p < .0001) compared to NP. Moreover, positive correlations between the expression levels of VEGF‐A and VEGFR‐2 (Spearman's coefficient ( r ) = .68, p = .013) and the expression levels of VEGF‐A and VEGFR‐2 proteins ( r = .8, p < .0001) were also observed in the NP samples. Additionally, the patients with PC exhibiting higher VEGFR‐2 expression levels experienced a shorter survival period ( p = .0372). Furthermore, we found an association between the microvascular density and overall survival. Dogs with a higher number of vessels showed a shorter survival time. We further demonstrated that the VEGF‐A and VEGFR‐2 exhibited high homology between humans and dogs, and identified their protein structures in both species. Conclusions: In conclusion, VEGFR‐2 appears to be an independent prognostic factor in animals with PC. VEGF‐A and VEGFR‐2 are highly conserved between humans and dogs, which can be investigated further in future cross‐species studies to explore their therapeutic applications.