Abstract
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 over-expression 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 signifi-cantly between the sporadic and VHL disease-associated hemangioblastomas.
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References
Latif F, Gnarra J, Tory K, et al (1993) Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 260:1317–1320
Friedrich CA (1999) Von Hippel-Lindau syndrome. Cancer 86:1658–1662
Wizigmann-Voos S, Breier G, Risau W et al (1995) Up-regulation of vascular endothelial growth factor and its receptors in von Hippel-Lindau disease-associated and sporadic hemangioblastomas. Cancer Res 55:1358–1364
Leung DW, Cachianes G, Kuang WJ, et al (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309
Keck P, Hauser SD, Krivi G, et al (1989) Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 246:1309–1312
Connolly DT, Heuvelman DM, Nelson R, et al. (1989) Tumor vascular permeability factor simulates endothelial cell growth and angiogenesis. J Clin Invest 84:1470–1478
Pietsch T, Valter MM, Wolf HK, et al (1997) Expression and distribution of vascular endothelial growth factor protein in human brain tumors. Acta Neuropathol (Berl) 93:109–117
van Meir EG, Porverini PJ, Chazin VR, et al (1994) Release of an inhibitor of angiogenesis upon induction of wild-type p53 expression in glioblastoma cells. Nature Genet 8:171–176
Miyagami M, Tazoe M, Nakamura S (1998) Expression of vascular endothelial growth factor and p53 protein in association with neovascularization in human malignant gliomas. Brain Tumor Pathol 15:95–100
Miyagami M, Kanou T, Nakamura S (1996) p53 protein expression and proliferative potential in non-recurrent and recurrent meningiomas. Brain Nerve 48:719–725
Melmon K, Rosen S (1964) Lindau's disease. Am J Med 36:595–617
Richard S, Campello C, Taillandier L (1998) Hemangioblastomas of the central nervous system in von Hippel-Lindau disease. French VHL Sudy Group. J Intern Med 243:547–553
Neumann HPH, Eggert HR, Weigel K, et al (1989) Hemangioblastomas of the central nervous system. A 10-year study with special reference to von Hippel-Lindau syndrome. J Neurosurg 70:24–30
Cramer F, Kimsey W (1952) The cerebellar hemangioblastomas. Review of 53 cases, with special reference to cerebellar cysts and the association of polycythemia. Arch Neurol Psychiat 67:237–252
Palmer JJ (1972) Hemangioblastomas: a review of 81 cases. Acta Neurochir 27:125–148
Silver ML, Hennigar G (1952) Cerebellar hemangioblastoma (hemangioblastoma). A clinicopathological review of 40 cases. J Neurosurg 9:484–494
Niemela M, Lim YJ, Scoderman M, et al (1996) Gamma knife radiosurgery in 11 hemangioblastomas. J Neurosurg 85:591–596
Chang SD, Meisel JA, Hancock SL, et al (1998) Treatment of hemangioblastomas in von Hippel-Lindau disease with linear accelerator-based radiosurgery. Neurosurgery 43:28–35
Maher ER, Yates JRW, Harries R, et al (1990) Clinical features and natural history of von Hippel-Lindau disease. Q J Med 77:1151–1163
Filling-Katz MR, Choyke PL, Oldfield E, et al (1991) Central nervous system involvement in von Hippel Lindau disease. Neurology 41:41–46
Neumann HP, Eggert HR, Sheremet R, et al (1992) Central nervous system lesions in von Hippel-Lindau syndrome. J Neurol Neurosurg Psychiat 55:898–901
Niemela M, Lemeta S, Summanen P, et al (1999) Long-term prognosis of hemangioblastoma of the CNS: impact of von Hippel-Lindau disease. Acta Neurchir (Wien) 141:1147–1156
Stratmann R, Krieg M, Haas R, et al (1997) Putative control of angiogenesis in hemangioblastomas by the von Hippel-Lindau tumor suppressor gene. J Neuropathol Exp Neurol 56:1242–1252
Morii K, Tanaka R, Washiyama K, et al (1993) Expression of vascular endothelial growth factor in capillary hemangioblastoma. Biochem Biophys Res Commun 194:749–755
Vaquero J, Zurita M, Coca S, et al (1998) Expression of vascular endothelial growth factor in cerebellar hemangioblastomas does correlate with tumor angiogenesis. Cancer Lett 132:213–217
Brown DF, Gazdar AF, White CL III, et al (1997) Human telomerase RNA expression and MIB-1 (Ki-67) proliferation index distinguish hemangioblastomas from metastatic renal cell carcinomas. J Neuropathol Exp Neurol 56:1349–1355
Iwata K, Nakagawa H, Hashizume Y (1996) Significance of MIB-1, PCNA indices, and p53 protein overexpression in intramedullary tumors of the spinal cord. Noshuyo Byori 13:73–78
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Miyagami, M., Katayama, Y. & Nakamura, S. Clinicopathological study of vascular endothelial growth factor (VEGF), p53, and proliferative potential in familial von Hippel-Lindau disease and sporadic hemangioblastomas. Brain Tumor Pathol 17, 111–120 (2000). https://doi.org/10.1007/BF02484282
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DOI: https://doi.org/10.1007/BF02484282