Clinicopathological study of vascular endothelial growth factor (VEGF), p53, and proliferative potential in familial von Hippel-Lindau disease and sporadic hemangioblastomas.

We examined the clinical characteristics and prognosis in six patients with familial von Hippel-Lindau (VHL) disease and seven with sporadic hemangioblastomas. The expression of vascular endothelial growth factor (VEGF), p53 protein, and proliferative potential with Ki67 monoclonal antibody (MIB-1) was compared using immunohistochemical methods between sporadic and VHL disease-associated hemangioblastomas. Patients with sporadic CNS hemangioblastomas were treated by total removal of the tumors, and they had a good long-term prognosis without neurological deficits on recurrence. However, patients with familial VHL disease often had multiple hemangioblastomas in the CNS and visceral tumors. Even if total removal of CNS hemangioblastomas in patients with VHL disease was performed initially, small multiple hemangioblastomas recurred during long-term follow-up in areas remote from the primary region resected by surgery. All of the hemangioblastomas displayed extensive overexpression of VEGF protein, with moderate to marked proliferation of blood vessels. The MIB-1 indices showed low values of 0.8% as the mean, with a range of 0.03%-2.1% for all the hemangioblastomas. None of the hemangioblastomas expressed p53 protein. The hemangioblastomas in patients with VHL disease were multiple in the CNS and were combined with visceral tumors. Patients with VHL disease had a poor long-term prognosis, in contrast to those with sporadic hemangioblastomas. The immunohistochemical findings for VEGF protein, p53 protein, and MIB-1 did not differ significantly between the sporadic and VHL disease-associated hemangioblastomas.