Hypoxia-inducible factor 1α expression does not differ between canine urothelial carcinoma and normal urinary bladder tissue.

Abstract

Objective: To evaluate the RNA and protein expression of hypoxia-inducible factor (HIF-1α) in canine urothelial carcinoma (UC) compared to normal canine urinary bladder tissue.

Methods: Dogs with normal urinary bladder tissue were enrolled at the time of euthanasia with the tissue obtained via necropsy within 1 hour after death. The high-grade UC tissue was collected via necropsy or cystoscopically utilizing a resectoscope. Dogs in the UC group were excluded if they were treated with chemotherapy or radiation therapy prior to tissue collection. Immunohistochemistry was performed on all tissues to evaluate intracytoplasmic and intranuclear immunoreactivity of HIF-1α using a semiquantitative immunoreactivity score (IRS). Ribonucleic acid sequencing was also performed to evaluate the expression of HIF-1α in normal urinary bladders and canine UC.

Results: 10 dogs with high-grade UC and 10 dogs with normal urinary bladder tissue were enrolled. The median intracytoplasmic HIF-1α in the UC group was mild in intensity with a low percentage of positive cells (median IRS, 1; range, 0 to 2). The control dogs had similar intracytoplasmic HIF-1α expression (median IRS, 1; range, 0 to 1). The difference in RNA expression of HIF-1α between groups was not significant (1.3-fold change).

Conclusions: This study did not identify any differential RNA or protein expression of HIF-1α between normal urinary bladder tissue and UC in dogs.

Clinical relevance: HIF-1α is not differentially expressed in canine UC, but further exploration is necessary to evaluate if other proteins associated with hypoxia and angiogenesis could play a role in tumor growth and chemotherapy resistance in canine UC.