The considerable progress in understanding the pathogenesis of RCC, along with the central role of the VHL/HIF/VEGF axis, have provided a foundation for the development of targeted therapies for advanced ccRCC.12-14 Under normal conditions, VHL serves as a tumor suppressor protein that has been shown to inversely regulate transcriptions factors, HIF-1α and HIF-2α, through ubiquitin-mediated proteasomal degradation, thereby preventing angiogenesis and tumor growth. This evidence concerns the gene VHL and nonpapillary renal cell carcinoma.