Expression of angiogenic factors in craniopharyngiomas: implications for tumor recurrence.
BACKGROUND
The primary treatment for craniopharyngiomas is total excision, but recurrence is common. However, current knowledge on the mechanisms of recurrence is limited.


OBJECTIVE
We hypothesized that recurrence is linked to the angiogenesis of the tumor. Recurrent and nonrecurrent tumor samples were compared with regard to expression of angiogenesis-related factors and angiogenic capacity in a corneal angiogenesis model.


METHODS
Specimens of 4 recurrent and 6 nonrecurrent tumors were selected from 57 patients with adamantinomatous craniopharyngiomas. Sections were immunohistochemically stained with antibodies for vascular endothelial growth factor (VEGF), fibronectin, fibroblast growth factor (FGF)-2, platelet-derived growth factor (PDGF)-A, PDGF-B, platelet-derived growth factor receptor (PDGFR)-alpha, and PDGFR-beta. Expression levels were graded using a 4-point scoring system and were compared. For corneal angiogenesis assay, tissue samples were inoculated in a micropocket created on the rat eye, and microvessels were counted on days 3, 5, 7, and 9 to evaluate angiogenic potential.


RESULTS
Expression of PDGFR-alpha and FGF-2 were significantly higher for recurrent tumors (P = .02 and P = .01). However, recurrent and nonrecurrent tumors did not differ in the expressions of other ligands and receptors (PDGF-A, PDGF-B, and PDGFR-beta). Recurrent tumors displayed a higher angiogenic potential starting from the fifth day of corneal angiogenesis assay.


CONCLUSIONS
These findings suggest a relationship between recurrence of craniopharyngiomas and angiogenesis. New treatment modalities with selective PDGFR-alpha blockers may represent a novel and effective therapeutic option for the treatment of craniopharyngiomas.
Sun
Halil Ibrahim
HI
Marmara University, Institute of Neurological Sciences, Molecular Neurosurgery Laboratory, Istanbul, Turkey.
Akgun
Emel
E
Bicer
Atilla
A
Ozkan
Abdulkadir
A
Bozkurt
Suheyla Uyar
SU
Kurtkaya
Ozlem
O
Koc
Demet Yalcinkaya
DY
Pamir
M Necmettin
MN
Kilic
Turker
T
D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D003397:Craniopharyngioma / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D009368:Neoplasm Transplantation; D010911:Pituitary Neoplasms / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
D043925:Angiogenesis Inducing Agents; D005353:Fibronectins; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2