Hypoxia-inducible factor-2α mRNA expression in human renal cell carcinoma

Abstract

Background. Hypoxia-inducible factor (HIF)-2α is upregulated in hypoxia or by inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene. In a number of malignancies, increased HIF-2α expression may indicate worse prognosis. The aim of this study was to evaluate the prognostic information of HIF-2α mRNA expression in renal cell carcinoma (RCC). Material and methods. HIF-2α mRNA was quantified by real time polymerase chain reaction (rt-PCR) in tumour tissue samples from 202 patients. Samples from 50 corresponding kidney cortex tissue were analysed as controls. mRNA levels were evaluated in relation to tumour cell type, TNM stage, nuclear grade and disease specific survival. Results. The levels of HIF-2α mRNA were significantly higher in 168 clear cell (c)RCC than in 23 papillary (p)RCC (p < 0.001) or 11 chromophobe (ch)RCC (p < 0.006). Among cRCC there was an inverse correlation between HIF-2α mRNA levels and TNM stage I and II-IV tumours (p=0.01), and nuclear grade (p = 0.006). After a median follow-up time of 99 months (range 34–247), 106 patients had died of RCC. No correlation of HIF-2α mRNA to survival was observed. A multivariate analysis of prognostic factors in cRCC showed that TNM stage alone was an independent predictor of prognosis; HIF-2α mRNA levels did not add further prognostic information. Discussion. The results demonstrated that HIF-2α mRNA levels were higher in cRCC compared to pRCC and chRCC. Furthermore, HIF-2α mRNA levels were inversely related to TNM stage and nuclear grade in cRCC.