Expression of VEGF and its receptor genes in intracranial schwannomas.
Vascular endothelial growth factor (VEGF) is considered to be a major regulator of angiogenesis in various brain tumors. In this study, we determined the expression levels of VEGF, and vascular endothelial growth factor receptor (VEGFR)-1 and -2 mRNA in 46 intracranial schwannomas by quantitative real-time PCR, and correlated these with various clinical factors or other molecular markers. We found that these tumors expressed significant amounts of VEGF mRNA in comparison with other brain tumors, including malignant gliomas and meningiomas. In addition, we performed immunohistochemical studies for VEGF and VEGFR-1, and confirmed that these tumors prominently express these proteins. The expression levels of VEGF and VEGFR-1 mRNA in recurrent tumors were higher than those in primary tumors. When we divided patients into two groups according to VEGF mRNA expression in the tumor, there was no significant difference in patient age, gender, or cranial nerves of origin between groups; however, the tumor volume tended to be larger in the high VEGF group than in the low VEGF group. The levels of VEGFR-1 mRNA and neurofibromatosis-2 mRNA in the high VEGF group were significantly greater than those in the low VEGF group. Levels of VEGFR-2 mRNA and DNA topoisomerase IIalpha mRNA, and the MIB-1 labeling index in the high VEGF group were slightly higher than those in the low VEGF group; however, the difference was not statistically significant. Based on these observations, the significance of VEGF and its receptor genes in intracranial schwannomas is discussed.
Uesaka
Toshio
T
Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Shono
Tadahisa
T
Suzuki
Satoshi O
SO
Nakamizo
Akira
A
Niiro
Hiroaki
H
Mizoguchi
Masahiro
M
Iwaki
Toru
T
Sasaki
Tomio
T
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003390:Cranial Nerve Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008579:Meningioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009442:Neurilemmoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025581:Neurofibromin 2 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D025581:Neurofibromin 2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D004250:DNA Topoisomerases, Type II