Expression of hypoxia inducible factor-1α and 2α in conventional renal cell carcinoma with or without sarcomatoid differentiation

Objectives: Expressions of hypoxia inducible factor (HIF)-1α and HIF-2α in epithelial and sarcomatoid components from the same patients with clear cell renal cell carcinoma (RCC) are lacking. We performed this study to define better the correlations among these molecules in RCC tissues. Materials and methods: Immunohistochemical staining of paraffin sections for HIF-1α and HIF-2α was performed in 24 cases of RCC with sarcomatoid differentiation using a streptavidin-peroxidase procedure. Control samples were collected from 58 patients with no sarcomatoid differentiation matched to cases by age, gender, and TNM stage. Results: HIF-1α was more expressed within the epithelial component of clear cell RCC with no sarcomatoid differentiation (82.8%) than within that with sarcomatoid differentiation (66.7%). HIF-2α was expressed in most of the epithelial component, regardless of the sarcomatoid differentiation. However, HIF-1α and HIF-2α were not expressed in the sarcomatoid component in about 50.0% of clear cell RCC regardless of the sarcomatoid differentiation. Multivariate Cox proportional hazards model analysis showed that HIF-1α expression was an independent predictor of cancer-specific survival in clear cell RCC with sarcomatoid differentiation (P = 0.029). Conclusions: HIF-1α and HIF-2α are not expressed in the sarcomatoid component in about a half of clear cell RCC with sarcomatoid differentiation, while HIF-2α was consistently overexpressed in the epithelial component in a majority of the tumors. Only HIF-1α expression regardless of tumor component is an independent prognostic factor in clear cell RCC with sarcomatoid differentiation.