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Positive expression of HIF-2alpha/EPAS1 in invasive bladder cancer
Guangbin Xia1, Yukio Kageyama, Tetsuo Hayashi
1Department of Urology and Reproductive Medicine, Graduate School Tokyo Medical and Dental University, Tokyo, Japan.
Objectives:
To investigate the expression of hypoxia-inducible factor (HIF)-2alpha/endothelial PAS domain protein 1 (EPAS1) in bladder cancer.
Methods:
Two bladder cancer cell lines (T24, EJ-1) were examined for the expression of HIF-2alpha/EPAS1 mRNA by reverse transcriptase-polymerase chain reaction and HIF-2alpha/EPAS1 protein by Western blot analysis, respectively. Expression of HIF-2alpha/EPAS1 protein was also investigated immunohistochemically on paraffin-embedded sections from 24 patients with bladder cancer.
Results:
HIF-2alpha/EPAS1 mRNA and protein could be detected in the two bladder cell lines under normoxia. The normal urothelium and all 7 superficial cases (pTis-pTa) were negative for HIF-2alpha/EPAS1. Five of the 8 pT1 cases (62.5%) and all 9 muscle-invasive cases were positive. The invasive compartment showed stronger HIF-2alpha/EPAS1 immunoreactivity compared with the superficial compartment. All the tumor clusters infiltrating to the interstitial tissue among muscle fibers showed moderate to strong positive staining.
Conclusions:
HIF-2alpha/EPAS1 is mostly expressed in invasive bladder cancer, which indicates a possible role for HIF-2alpha/EPAS1 in the invasion of bladder cancer.