TY - JOUR
T1 - Difference in CXCR4 expression between sporadic and VHL-related hemangioblastoma
AU - Kruizinga, Roeliene C
AU - van Marion, Denise M S
AU - den Dunnen, Wilfred F A
AU - de Groot, Jan C
AU - Hoving, Eelco W
AU - Oosting, Sjoukje F
AU - Timmer-Bosscha, Hetty
AU - Derks, Rosalie P H
AU - Cornelissen, Chantal
AU - van der Luijt, Rob B
AU - Links, Thera P
AU - de Vries, Elisabeth G E
AU - Walenkamp, Annemiek M E
PY - 2016/10
Y1 - 2016/10
N2 - 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.
AB - 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.
KW - CXCR4
KW - CXCL12
KW - Hemangioblastomas
KW - VEGF
KW - VHL
U2 - 10.1007/s10689-016-9879-3
DO - 10.1007/s10689-016-9879-3
M3 - Article
C2 - 26920352
SN - 1389-9600
VL - 15
SP - 607
EP - 616
JO - Familial Cancer
JF - Familial Cancer
IS - 4
ER -