Abstract: Background -Tumor microenvironment and variable gene expression plays an important role in tumor growth and can mediate chemotherapy resistance. Hypoxia-inducible factor (HIF-1α) is increased in urothelial carcinoma (UC) in people and is negatively correlated with survival. Urothelial carcinoma (UC) is the most common urinary bladder neoplasia in dogs, but HIF-1α has not been investigated in this canine tumor.Hypothesis/Objectives -We hypothesized that HIF-1α will be increased in canine UC when compared to normal canine urinary bladder tissue.Animals –Ten dogs with confirmed UC, and ten dogs in the control group with normal urinary bladders.Methods –Normal urinary bladder or UC was confirmed on hematoxylin-eosin stained tissue and uroplakin-3 IHC. Immunohistochemistry was then performed on paraffin sections though incubation with the primary antibodies against HIF-1α. Immunolabeled slides were examined and a semiquantitative immunoreactivity score was applied in which intranuclear labeling of HIF-1α was considered positive (0-3+; Table 1).Results -Positive intranuclear labeling for HIF-1α was observed in 5 (50%) of the UC samples, and was scored as 1+ in these 5 with less than 10% of cells displaying positivity. All of the normal bladder tissue displayed intranuclear labeling for HIF-1α, with 9/10 scored 1+, and the tenth being 2+ with moderate intensity.Conclusions and Clinical Importance –There is variable expression of HIF-1α in dogs with UC, with more consistent expression of HIF-1α seen in normal canine bladder tissue. Further investigation of this transcription factor through RNA sequencing of canine UC tissue for genes encoding for HIF-1α is ongoing.
