Expression of hypoxia inducible factor-1 alpha in matched hormone naive and castrate resistant prostate cancer specimens

摘要

Hypoxia inducible factor-1 alpha (HIF-1α) is known as an important transcription factor in endocrine tumours. It is elevated in hypoxic tumour microenvironment, increasing angiogenesis and enabling tumour cells to enter the circulation. We therefore hypothesised that patients with advanced prostate cancer disease have high tumoural HIF-1α xpression and worse disease specific survival. Aim of this study was to assess expression of HIF-1α in prostate cancer specimens taken before and after castrate resistance to address its cellular location and to examine if this is associated with clinicopathological features and clinical outcome of the particular prostate cancer cohort. 50 pairs of hormone naive and castrate resistant prostate cancer specimens were analysed employing tissue microarray technology. Immunohistochemistry was performed using an antibody to HIF-1α.HIF-1α expression was observed in both, cytoplasm and nucleus. Cytoplasmic HIF-1α expression correlated positively with metastases at diagnosis (p=0.005), whereas nuclear HIF-1α expression correlated with metastases at relapse (p=0.041). Cytoplasmic and nuclear HIF-1α expression did not change from hormone naive to hormone castrate resistant tumours. No significant association was observed in this study between tumoural HIF-1α expression, biochemical relapse and patient survival. HIF-1α was associated with the presence of metastases at time of diagnosis and time of relapse. HIF-1α is likely to play a role in progressive prostate cancer.