title: Difference in CXCR4 expression between sporadic and VHL-related hemangioblastoma.
abstract: Central nervous system hemangioblastomas occur sporadically and in patients with von Hippel-Lindau (VHL) disease due to a VHL germline mutation. This mutation leads to enhanced transcription of chemokine receptor 4 (CXCR4), its ligand (CXCL12) and vascular endothelial growth factor A (VEGFA). We aimed to determine in VHL-related and sporadic hemangioblastomas CXCR4, CXCL12, and VEGFA protein expression and to correlate this to hemangioblastoma size and expression in normal surrounding tissue. 27 patients with a hemangioblastoma were included for analysis of immunohistochemistry of tissue, MRI and DNA. Hemangioblastomas overexpress CXCR4, CXCL12, and VEGFA compared to normal surrounding tissue. In sporadic hemangioblastomas the mean percentage of CXCR4 positive hemangioblastoma cells was 16 %, SD 8.4, in VHL-related hemangioblastomas 8 %, SD 4.4 (P = 0.002). There was no relation between preoperative tumor size and CXCR4 or CXCL12 expression. Compared to normal surrounding tissue CXCR4, CXCL12, and VEGFA were overexpressed in hemangioblastomas. Most interestingly, sporadic hemangioblastomas overexpress CXCR4 compared to VHL-related hemangioblastoma.
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.|Department of Endocrinology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Roeliene C
authors.initials: RC
authors.lastname: Kruizinga
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Denise M S
authors.initials: DM
authors.lastname: van Marion
authors.affiliation: Department of Pathology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Wilfred F A
authors.initials: WF
authors.lastname: den Dunnen
authors.affiliation: Department of Radiology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Jan C
authors.initials: JC
authors.lastname: de Groot
authors.affiliation: Department of Neurosurgery, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Eelco W
authors.initials: EW
authors.lastname: Hoving
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Sjoukje F
authors.initials: SF
authors.lastname: Oosting
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Hetty
authors.initials: H
authors.lastname: Timmer-Bosscha
authors.affiliation: Department of Radiology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Rosalie P H
authors.initials: RP
authors.lastname: Derks
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, P.O. Box 85.500, 3508 GA, Utrecht, The Netherlands.
authors.forename: Chantal
authors.initials: C
authors.lastname: Cornelissen
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, P.O. Box 85.500, 3508 GA, Utrecht, The Netherlands.
authors.forename: Rob B
authors.initials: RB
authors.lastname: van der Luijt
authors.affiliation: Department of Endocrinology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Thera P
authors.initials: TP
authors.lastname: Links
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands. a.walenkamp@umcg.nl.
authors.forename: Annemiek M E
authors.initials: AM
authors.lastname: Walenkamp
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000473:pathology; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018325:Hemangioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human
keywords: CXCL12; CXCR4; Hemangioblastomas; VEGF; VHL