HIF1A and neoplasm: Moreover, the extent of HIF-1α and CAIX staining can be influenced by the proliferation status of the hypoxic tumor cells [40] and their metabolic and physiological microenvironments, including the level of reactive oxygen and nitrogen species, lowered extracellular pH and glucose and bicarbonate deprivation, and the concentrations of some growth factors and cytokines [28, 32, 41, 42].