Hypoxia is one of the most important contributing factors in the tumor microenvironment, stimulating tumor dedifferentiation and angiogenesis.33 In this regard, the expression of HIF-2α has been proposed to be associated with dedifferentiation of NB, which may depend on its angiogenic property rather than cell-cycle modulation.34 TLX is reported to act as a hypoxia-inducible proangiogenic switch molecule, strongly expressed in postnatal proangiogenic retinal astrocytes, which secrete vascular endothelial growth factor (VEGF) and fibronectin. This evidence concerns the gene EPAS1 and neuroblastoma.