Difference in CXCR4 expression between sporadic and VHL-related hemangioblastoma

Roeliene C Kruizinga; Denise M S van Marion; Wilfred F A den Dunnen; Jan C de Groot; Eelco W Hoving; Sjoukje F Oosting; Hetty Timmer-Bosscha; Rosalie P H Derks; Chantal Cornelissen; Rob B van der Luijt; Thera P Links; Elisabeth G E de Vries; Annemiek M E Walenkamp

doi:10.1007/s10689-016-9879-3

Difference in CXCR4 expression between sporadic and VHL-related hemangioblastoma

Fam Cancer. 2016 Oct;15(4):607-16. doi: 10.1007/s10689-016-9879-3.

Authors

Affiliations

¹ Department of Medical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
² Department of Endocrinology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
³ Department of Pathology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
⁴ Department of Radiology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
⁵ Department of Neurosurgery, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
⁶ Department of Medical Genetics, University Medical Center Utrecht, P.O. Box 85.500, 3508 GA, Utrecht, The Netherlands.
⁷ 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.

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.

Keywords: CXCL12; CXCR4; Hemangioblastomas; VEGF; VHL.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Cerebellar Neoplasms / genetics*
Cerebellar Neoplasms / pathology
Chemokine CXCL12 / genetics
Chemokine CXCL12 / metabolism
Female
Gene Expression Regulation, Neoplastic
Hemangioblastoma / genetics*
Hemangioblastoma / pathology
Humans
Male
Middle Aged
Mutation
Receptors, CXCR4 / genetics*
Receptors, CXCR4 / metabolism
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism
Von Hippel-Lindau Tumor Suppressor Protein / genetics*
Von Hippel-Lindau Tumor Suppressor Protein / metabolism
Young Adult

Substances

CXCL12 protein, human
CXCR4 protein, human
Chemokine CXCL12
Receptors, CXCR4
VEGFA protein, human
Vascular Endothelial Growth Factor A
Von Hippel-Lindau Tumor Suppressor Protein
VHL protein, human