EPAS1 and nonpapillary renal cell carcinoma: Studies of multiple pre-cancerous renal lesions in patients with familial VHL disease show a switch to HIF-2α expression in lesions with more neoplastic pathological features [12,30]; not infrequently HIF-2α is the only isoform expressed in advanced ccRCC, and in many ccRCC lines [11,16,18,31].