Introduction: Patients with von Hippel-Lindau disease (VHL) develop a multitude of highly vascular and cystic tumors. It has been proposed that the vascular nature of these tumors is the product of reactive angiogenesis, secondary to unregulated Hypoxia Inducible Factor (HIF) activity and subsequent overexpression of Vascular Endothelial Growth Factor (VEGF) and Platelet-Derived Growth Factor (PDGF?) in neoplastic tumor cells. However, a recent study has shown that the characteristic islands of erythrocytes in VHL-associated CNS hemangioblastoma tumors are developmentally-derived directly from tumor cells. Furthermore, the hemangioblasts cell, identified as the probable neoplastic cell in hemangioblastomas, maintains the capacity to differentiate into both endothelial cells and erythrocytes.
Methods: 3D immunofluorescence staining, loss of heterozygosity (LOH), and fluorescence in situ hybridization (FISH) were used to explore the relationship of VHL status with the vasculature of VHL-associated lesions.
Results: Utilizing 3D immunofluorescence staining and LOH, we reinforced the results of prior studies. With FISH, we demonstrated that the isolated vascular structures and blood vessels within VHL-associated lesions are a result of tumor-derived vasculogenesis.
Conclusions: Our FISH findings provide confirmatory evidence that embryologic, developmentally arrested hemangioblasts are the precursor cells responsible for VHL-associated tumor development.
Patient Care: The implications of this research is for novel targeting of VHL-deficient vessels to inhibit tumor progression.
Learning Objectives: By the conclusion of this session, participants should be able to:
1. Describe the two prevailing hypotheses of vasculogenesis in VHL-associated tumors
2. Identify how new research confirms the VHL-derived vasculogenesis hypothesis
3. Recognize the implications of this research for novel targeting of VHL-deficient vessels to inhibit tumor progression