AIM: Angiogenesis plays a central role in the growth of a tumor. The hypoxia-inducible factor 1alpha (HIF-1alpha) is a regulated subunit of HIF-1, a key factor that carries fundamental features in angiogenesis and tumor progression. Renal cell carcinoma (RCC) is highly vascularized with a variable clinical outcome, having specific genetic alterations in different RCC types. This study investigated HIF-1alpha mRNA and protein expression in relation to RCC type and clinicopathological variables including clinical stage and survival.METHODS: Quantitative analysis of HIF-1alpha mRNA expression in 202 patients including 168 clear cell (cRCC), 23 papillary (pRCC) and 11 chromophobe RCCs. Additionally, 49 samples from non-malignant corresponding kidney cortex were analysed. Comparative analysis of HIF-1alpha protein expression was performed by immunohistochemistry of tissue microarray.RESULTS: HIF-1alpha mRNA levels were significantly lower in cRCC compared with pRCC (P = 0.001) and kidney cortex (P < 0.001). In cRCC, HIF-1alpha mRNA was correlated to gender and age. For pRCC there was no correlation between HIF-1alpha mRNA and tumor stage, nuclear grade, age, tumor size or gender. HIF-1alpha mRNA expression was inversely related to HIF-1alpha protein levels in pRCC (P = 0.041) but not significantly in cRCC (P = 0.075).CONCLUSION: HIF-1alpha mRNA levels were significantly lower in cRCC copmpared with kidney cortex and the other RCC types. High HIF-1alpha protein expression appeared to suppress HIF-1alpha mRNA expression, distressing the HIF-1 pathway in RCC.