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

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

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

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 language	English
Pages (from-to)	607-16
Number of pages	10
Journal	Familial Cancer
Volume	15
Issue number	4
DOIs	https://doi.org/10.1007/s10689-016-9879-3
Publication status	Published - Oct 2016
Externally published	Yes

Keywords

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

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10.1007/s10689-016-9879-3

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Kruizinga, R. C., van Marion, D. M. S., den Dunnen, W. F. A., de Groot, J. C., Hoving, E. W., Oosting, S. F., Timmer-Bosscha, H., Derks, R. P. H., Cornelissen, C., van der Luijt, R. B., Links, T. P., de Vries, E. G. E., & Walenkamp, A. M. E. (2016). Difference in CXCR4 expression between sporadic and VHL-related hemangioblastoma. Familial Cancer, 15(4), 607-16. https://doi.org/10.1007/s10689-016-9879-3

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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.",

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

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

note = "Publisher Copyright: {\textcopyright} 2016, The Author(s).",

year = "2016",

month = oct,

doi = "10.1007/s10689-016-9879-3",

language = "English",

volume = "15",

pages = "607--16",

journal = "Familial Cancer",

issn = "1389-9600",

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Kruizinga, RC, van Marion, DMS, den Dunnen, WFA, de Groot, JC, Hoving, EW, Oosting, SF, Timmer-Bosscha, H, Derks, RPH, Cornelissen, C, van der Luijt, RB, Links, TP, de Vries, EGE & Walenkamp, AME 2016, 'Difference in CXCR4 expression between sporadic and VHL-related hemangioblastoma', Familial Cancer, vol. 15, no. 4, pp. 607-16. https://doi.org/10.1007/s10689-016-9879-3

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 - Adolescent

KW - Adult

KW - Aged

KW - Cerebellar Neoplasms/genetics

KW - Chemokine CXCL12/genetics

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Hemangioblastoma/genetics

KW - Humans

KW - Male

KW - Middle Aged

KW - Mutation

KW - Receptors, CXCR4/genetics

KW - Vascular Endothelial Growth Factor A/genetics

KW - Von Hippel-Lindau Tumor Suppressor Protein/genetics

KW - Young Adult

UR - https://www.scopus.com/pages/publications/84975757948

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 -

Difference in CXCR4 expression between sporadic and VHL-related hemangioblastoma

Abstract

Keywords

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