OBJECTIVE To evaluate transcription factor hypoxia inducible factor‐1α (HIF‐1α) activity, by analysing a target gene for HIF‐1α, glucose transporter‐1 (GLUT‐1), using a tissue microarray (TMA) in different types of renal cell carcinoma (RCC, a tumour with a variable clinical course, partly due to angiogenic activity), as angiogenesis is important for tumour progression and metastatic spread, and is activated by hypoxia. PATIENTS AND METHODS GLUT‐1 and HIF‐1α expressions were semiquantitatively analysed using immunohistological staining of a prepared TMA, using samples from 187 patients, including 148 with conventional, 26 with papillary and 13 with chromophobe RCC. RESULTS GLUT‐1 staining was found mainly in the cytoplasm. The tumours were subdivided into GLUT −1LOW and GLUT‐1HIGH, based on staining intensity. There was a significant difference in GLUT‐1 expression between RCC types (P < 0.05). In conventional RCC, GLUT‐1 had no correlation with clinicopathological variables. By contrast there was a correlation with tumour stage in papillary RCC. There was an insignificant trend to better survival of patients with GLUT‐1LOW expression in both conventional and papillary RCC. GLUT‐1 correlated significantly (P = 0.008) with HIF‐1α. CONCLUSIONS Most patients with conventional RCC had GLUT‐1HIGH staining and there was a significant correlation with HIF‐1α. In papillary RCC, GLUT‐1 expression was associated with stage; GLUT‐1 expression was significantly higher in conventional RCC than in papillary and chromophobe RCC. GLUT‐1LOW in both papillary and conventional RCC appeared to correspond with a better prognosis.

No abstract

Purpose: Renal cell carcinoma (RCC) is the most common malignancy of the kidney composed of specific tumor types. The sporadic conventional RCCs are, in contrast to the other RCC types, characterized by a high rate of von Hippel-Lindau (VHL) mutations and hypermethylation. The majority of these tumors lack functional VHL protein (pVHL) that leads to increased hypoxia-inducible factor 1α (HIF-1α) expression. The pVHL is the physiologic regulator of the activity of HIF-1α by targeting it to the proteasome for degradation under normoxia. Both pVHL and HIF-1α target other genes that are important for cancer survival and proliferation. Expression of HIF-1α has been linked to poor prognosis in different malignancies, although few studies have been done on the relation between HIF-1α and clinical variables in RCC. Experimental Design: HIF-1α protein expression was analyzed in tumor tissue from 92 patients with RCC. HIF-1α was quantified by Western blot relative to a positive control. Results: The HIF-1α protein was expressed as two bands which strongly correlated (r = 0.906, P &lt; 0.001); therefore, they were added and the sum evaluated against clinicopathologic variables. There was no association between HIF-1α and gender, stage, grade, tumor size, or vein invasion. Conventional RCCs had significantly higher HIF-1α expression compared with papillary and chromophobe RCCs and kidney cortex. In conventional RCC, HIF-1α was an independent prognostic factor. Conclusion: HIF-1α levels varied significantly between the different RCC types. In conventional RCC, HIF-1α was an independent prognostic factor. These data indicate that HIF-1α is involved in tumorogenesis and progression of RCC. Evaluation of other HIF target gene products and correlation to angiogenesis seems warranted.

No abstract