Moreover, Von-Hippel-Lindau (VHL) mutations in ccRCC patients with antiangiogenic therapies induce a hypoxia-inducible factor (HIF)alpha accumulation, also activating alternative HIF and/or non HIF-mediated proangiogenic signaling pathways in the tumor, such as fibroblast growth factor (FGF), placental growth factor (PIGF), ephrin and angiopoietin [5]. Here, VHL is linked to nonpapillary renal cell carcinoma.