VEGF-C, VEGF-D and VEGFR-3 expression in peripheral neuroblastic tumours.
OBJECTIVE
More than 50% of neuroblastomas (NBs) present with haematogenous and/or lymphatic metastasis; however, little is known about the clinicopathological significance in NBs of the key lymphangiogenesis growth factors vascular endothelial growth factor (VEGF)-C and VEGF-D and the receptor VEGFR-3.


RESULTS
Ninety-three NBs and nine ganglioneuromas (GNs) were immunostained for VEGF-C, VEGF-D and VEGFR-3. VEGF-C and VEGF-D were present in 76% and 82% of the NBs, respectively. There was no significant difference in VEGF-C expression between NBs and GNs. VEGF-D expression was significantly higher in NBs compared with GNs and in MYCN-amplified NBs. VEGFR-3 tumoral cell expression (VEGFR-3c), present in 48% of the NBs, was significantly higher in NBs from children ≥ 18 months at presentation and those belonging to a high-risk group. VEGFR-3 lymphovascular density was increased significantly in NBs compared with GNs and in NBs associated with adverse clinicopathological and biological factors. Lymphovascular invasion, assessed in VEGFR-3-stained vessels, was present in ∼50% of NBs. Cox regression analyses demonstrated that VEGFR-3c expression was associated with a significantly shorter event-free survival and that its effect was independent of the important pathological variable, mitosis-karyorrhexis index.


CONCLUSIONS
VEGF-D and VEGFR-3 up-regulation support tumour progression in NB and VEGFR-3c may provide a useful prognostic marker in NBs.
School of Cellular and Molecular Medicine, University of Bristol, School of Medical Sciences, University Walk, Bristol, UK. pramila.ramani@bristol.ac.uk
Pramila
P
Ramani
Rachel
R
Nash
Lucy
L
Radevsky
Ameesh
A
Patel
Michael
M
Luckett
Chris
C
Rogers
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005729:Ganglioneuroma / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D042583:Lymphangiogenesis / Q000502:physiology; D009447:Neuroblastoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D010524:Peripheral Nervous System Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D015854:Up-Regulation; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism*; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D040321:Vascular Endothelial Growth Factor Receptor-3