Disease relevance of Hemangioblastoma

• Germ-line mutations of the von Hippel-Lindau tumor suppressor gene (VHL) predispose individuals to a variety of human tumors, and somatic mutations of this gene have been identified in sporadic renal cell carcinomas and cerebellar hemangioblastomas [1].
• Germline mutations in the von Hippel-Lindau tumor suppressor gene (VHL) predispose individuals to a variety of tumors, including renal carcinoma, hemangioblastoma of the central nervous system, and pheochromocytoma [2].
• Differential expression in glioblastoma multiforme and cerebral hemangioblastoma of cytoplasmic proteins that bind two different domains within the 3'-untranslated region of the human glucose transporter 1 (GLUT1) messenger RNA [3].
• Secondary erythrocytosis due to a cerebellar hemangioblastoma: demonstration of erythropoietin mRNA in the tumor [4].
• Case 2. Hemangioblastomas: diagnosis of von Hippel-Lindau disease and antiangiogenic treatment with SU5416 [5].

High impact information on Hemangioblastoma

• The glucose transporter 1 (GLUT1) protein is underexpressed in human glioblastoma multiforme and is overexpressed in human cerebral hemangioblastoma [3].
• In situ hybridization confirmed the presence of VEGPF mRNA in tumor cells and its increased abundance in capillary hemangioblastomas [6].
• However, Epo expression in hemangioblastomas was observed only in individual cases, and the analyses were mainly based on indirect determination of erythropoiesis-stimulating activity [7].
• In situ hybridization revealed neoplastic stromal cells as Epo- and VEGF-producing cells in hemangioblastomas [7].
• HIF-1alpha was detected in tumor cell nuclei of both hemangioblastomas and CC-RCCs [8].

Chemical compound and disease context of Hemangioblastoma

• We observed, after 3 to 4 months of treatment, secondary paradoxical polycythemia in 3 VHL patients with CNS or retinal hemangioblastomas treated by the anti-VEGF receptor SU5416 [9].
• Prednisolone induced increased levels of enzyme activity in most cultures, and sodium butyrate acted as an inducer in cultures of pituitary adenoma and hemangioblastoma cells [10].
• This study examined the relationship between arterial blood pressure and plasma norepinephrine levels during 12 hours of monitored sleep in a 35-year-old man in whom neurogenic hypertension developed immediately after surgical removal of a large hemangioblastoma at the obex region of the cervical-medullary junction [11].
• Nineteen hemangioblastomas, nine angioblastic meningiomas, ten metastases to the brain (including five renal cell carcinomas), and five primary renal cell carcinomas were studied using the immunoperoxidase method for Factor VIII related antigen and glial fibrillary acidic protein (GFAP) [12].
• CONCLUSIONS: Thallium-201 washout is significantly faster in hemangioblastomas [13].

Biological context of Hemangioblastoma

• Hypermethylation of the VHL gene was detected in 33% (6/18) of tumors without LOH, including 2 RCCs and 4 hemangioblastomas [14].
• The results suggest that allelic losses and mutations of the VHL tumor suppressor gene play a role in sporadic cerebellar hemangioblastoma tumorigenesis [15].
• Up-regulation of vascular endothelial growth factor and its receptors in von Hippel-Lindau disease-associated and sporadic hemangioblastomas [16].
• To determine the molecular pathogenesis of tumor formation in this setting, we analyzed five central nervous system hemangioblastomas from three patients of a single VHL germline deletion kindred, all displaying mild clinical phenotype [17].
• Reconsideration of biallelic inactivation of the VHL tumour suppressor gene in hemangioblastomas of the central nervous system [18].

Anatomical context of Hemangioblastoma

• In an erythrocytotic patient with a cerebellar hemangioblastoma we found elevated levels of Ep in the tumor cyst fluid and for the first time demonstrated Ep mRNA in the tumor by Northern blotting [4].
• High expression of the Glut1 glucose transporter in human brain hemangioblastoma endothelium [19].
• Because nestin is highly expressed in growing endothelial cells, we examined its expression in hemangioblastomas because hemangioblasts are thought to be a precursor for angiogenic epithelial cells [20].
• CONCLUSIONS: We report rapid, extensive, and durable recovery of visual function after systemic administration of the VEGF receptor inhibitor SU5416 to a patient with VHL syndrome and optic nerve head hemangioblastoma [21].
• The authors present four patients with no family history or clinical evidence of VHL syndrome in whom extensive, progressive, en plaque coating of the brainstem and spinal cord with hemangioblastomas developed 1 to 8 years after complete resection of a solitary cerebellar hemangioblastoma [22].

Gene context of Hemangioblastoma

• The inactivation of the von Hippel-Lindau (VHL) gene predisposes affected individuals to VHL syndrome and is an early genetic event associated with sporadic renal cell carcinoma and CNS hemangioblastomas [23].
• These results suggest that in the nonhypoxic microenvironment of hemangioblastoma, Epo, similar to VEGF, might be negatively regulated by the VHL gene product [7].
• Our findings suggest that autocrine and/or juxtacrine growth stimulation via the EGFR may contribute to tumor growth in capillary hemangioblastomas [24].
• Ten hemangioblastomas of the central nervous system were examined by an immunoperoxidase technique for glial fibrillary acidic protein (GFAP), S-100 protein, and Factor VIII-related antigen to determine the origin of the stromal cells [25].
• All of the hemangioblastomas demonstrated PR immunoreactivity, whereas 10 of 12 primary RCCs were negative [26].

Analytical, diagnostic and therapeutic context of Hemangioblastoma

• The cytologic features of a hemangioblastoma of the spinal cord diagnosed by an intraoperative fine needle aspiration (FNA) biopsy are reported in a 66-year-old man with a long-standing history of Charcot-Marie-Tooth disease [27].
• The identification of VHL mutations and subsequent screening allows early diagnosis and treatment of asymptomatic retinal or central nervous system hemangioblastomas, as well as other malignancies associated with this syndrome [28].
• Since 1960, 17 patients with von Hippel-Lindau disease have had cerebellar hemangioblastomas removed at the Victoria General Hospital, Halifax, Nova Scotia. The 4 most recent patients have had renal arteriography as a part of their investigation [29].

References