VHL and neoplasm: In conventional RCC, HIF-1α immunoreactivity is observed in cells throughout the tumor, consistent with HIF activation being caused by loss of VHL tumor suppressor function rather than microenvironmental hypoxia.[10] Therefore, these results confirmed the report of Yao et al.,[5] who demonstrated that RCC without VHL alteration had a poorer prognosis than RCC with VHL alteration.