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

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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.

Original languageEnglish
Pages (from-to)607-616
Number of pages10
JournalFamilial Cancer
Volume15
Issue number4
Early online date26-Feb-2016
DOIs
Publication statusPublished - Oct-2016

Keywords

  • CXCR4
  • CXCL12
  • Hemangioblastomas
  • VEGF
  • VHL
  • HIPPEL-LINDAU-DISEASE
  • CHEMOKINE RECEPTOR CXCR4
  • TUMOR-SUPPRESSOR GENE
  • CENTRAL-NERVOUS-SYSTEM
  • RENAL-CELL-CARCINOMA
  • CEREBELLAR HEMANGIOBLASTOMAS
  • BREAST-CANCER
  • CAPILLARY HEMANGIOBLASTOMAS
  • ANTAGONIST CTCE-9908
  • MOLECULAR PATHOLOGY

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