The VEGF/VEGF-R axis in sporadic vestibular schwannomas correlates with irradiation and disease recurrence.
OBJECTIVE
The molecular mechanisms downstream of mutated neurofibromatosis type 2 (NF2) gene resulting in the growth and development of vestibular schwannoma (VS) are controversial. Several lines of evidence suggest the involvement of the vascular endothelial growth factor (VEGF) pathway in VS development. Given that recent studies of VEGF blockade in patients with NF2-associated VS showed positive effects on VS growth control, we initiated this comprehensive study of the VEGF pathway in sporadic VS.


METHODS
A tissue microarray analysis of 182 sporadic VS was conducted. The expression of VEGF and its receptors as well as the proliferative activity of the tumors were quantified. The expression data were correlated to tumor volumes and diameters as well as to tumor recurrence and previous irradiation.


RESULTS
All studied tumors expressed VEGF and its receptors. Proliferative activity was related to the growth characteristics of the tumors. Moreover, we found significantly higher VEGF levels in recurrent tumors (p = 0.0387) and in preoperatively irradiated tumors (p = 0.0213).


CONCLUSIONS
Our data suggest a relevant role of the VEGF pathway in VS growth and therapy outcome. Therefore, targeting this pathway using antiangiogenic compounds might be beneficial for patients with sporadic VS, especially those with recurrent or irradiated tumors.
Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Germany.
D
D
Koutsimpelas
M
M
Bjelopavlovic
R
R
Yetis
K
K
Frauenknecht
B
B
Adryan
I
I
Schmidtmann
H
H
Gouveris
K
K
Fruth
U R
UR
Heinrich
R H
RH
Stauber
W J
WJ
Mann
J
J
Brieger
D000293:Adolescent; D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D009464:Neuroma, Acoustic / Q000532:radiotherapy* / Q000601:surgery; D039942:Neuropilin-1 / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D046888:Tissue Array Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D055815:Young Adult
D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D040262:Receptors, Vascular Endothelial Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2