Von Hippel-Lindau (VHL) disease is a hereditary
tumor syndrome that targets a highly selective subset of organs causing specific types of
tumors. The
biological basis for this principle of organ selectivity and
tumor specificity is not well understood. VHL-associated
hemangioblastomas share similar molecular and morphological features with embryonic blood and vascular precursor cells. Therefore, we suggest that VHL
hemangioblastomas are derived from developmentally arrested hemangioblastic lineage keeping their potential of further differentiation. Due to these common features, it is of major interest to investigate whether VHL-associated
tumors other than
hemangioblastoma also share these pathways and molecular features. The expression of hemangioblast
proteins has not yet been assessed in other VHL-related
tumors. To gain a better understanding of VHL
tumorigenesis, the expression of hemangioblastic
proteins in different VHL-associated
tumors was investigated. The expression of embryonic hemangioblast
proteins Brachyury and TAL1 (
T-cell acute lymphocytic leukemia protein 1) was assessed by immunohistochemistry staining on 75 VHL-related
tumors of 51 patients: 47
hemangioblastomas, 13 clear cell
renal cell carcinomas, 8
pheochromocytomas, 5 pancreatic
neuroendocrine tumors, and 2
extra-adrenal paragangliomas.
Brachyury and TAL1 expression was, respectively, observed in 26% and 93% of cerebellar
hemangioblastomas, 55% and 95% of spinal
hemangioblastomas, 23% and 92% of clear cell
renal cell carcinomas, 38% and 88% of
pheochromocytomas, 60% and 100% of pancreatic
neuroendocrine tumors, and 50% and 100% of
paragangliomas. We concluded that the expression of hemangioblast
proteins in different VHL-associated
tumors indicates a common embryological origin of these lesions. This may also explain the specific topographic distribution of VHL-associated
tumors.