Expression and localization of hypoxia proteins in prostate cancer: prognostic implications after radical prostatectomy.

ABSTRACT

OBJECTIVES: To uncover novel biomarkers that will help predict which patients are at risk and may guide future treatment decisions. A significant proportion of prostate cancer patients treated with radical prostatectomy will experience a recurrence of the disease. Given the substantial role of hypoxia in prostate cancer development and treatment, this investigation focuses on the Hypoxia Inducible Factor (HIF-1alpha) pathway. METHODS: A tissue microarray was constructed of prostate cancer tissue collected from 71 patients undergoing radical prostatectomy. The expression of proteins involved in the HIF-1alpha pathway was investigated by an immunohistochemical approach and correlated to clinical features including the time to biochemical recurrence. RESULTS: Expression of GLUT1 correlated significantly (P <.05) with a shorter time to biochemical recurrence after radical prostatectomy and was independent from the Gleason grade and stage of cancer. Furthermore, our studies revealed for the first time that accumulation of prolyl-4-hydroxylases 1 especially in the nucleus, is a significant indicator for a worse prognosis (P <.001). CONCLUSIONS: This study confirms the upregulation of proteins involved in the HIF-1alpha hypoxia pathway in prostate cancer cells, indicative of a hypoxic tumor state. Importantly, we report the identification of 2 novel markers, GLUT1 and prolyl-4-hydroxylases 1, with prognostic significance for patients undergoing radical prostatectomy.