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Journal of Neuro-Oncology

, Volume 83, Issue 3, pp 259–266 | Cite as

Expression of VEGF and its receptor genes in intracranial schwannomas

  • Toshio Uesaka
  • Tadahisa Shono
  • Satoshi O. Suzuki
  • Akira Nakamizo
  • Hiroaki Niiro
  • Masahiro Mizoguchi
  • Toru Iwaki
  • Tomio Sasaki
Laboratory Investigation

Abstract

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 IIα 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.

Keywords

Intracranial schwannoma mRNA Real-time PCR VEGF VEGFR-1 VEGFR-2 

Notes

Acknowledgments

We thank Tomomi Yamada, MS (Department of Medical Information Science, Kyushu University Hospital) for her invaluable assistance in statistical analysis, and Saori Uchida for her excellent technical assistance, Mikiko Hidaka and Emiko Uchiyama (Department of Neurosurgery, Kyushu University Graduate School of Medical Sciences) for assistance with manuscript preparation.

References

  1. 1.
    Woodruff JM, Kourea HP, Louis DN, Scheithauer BW (2000) Schwannoma. In: Kleihues P, Cavenee WK (eds) Pathology and genetics of tumors of the nervous system. International Agency for Reseach on Cancer Press, Lyon, pp 164–166Google Scholar
  2. 2.
    Herwadker A, Vokurka EA, Evans DG, Ramsden RT, Jackson A (2005) Size and growth rate of sporadic vestibular schwannoma: predictive value of information available at presentation. Otol Neurotol 26:86–92PubMedCrossRefGoogle Scholar
  3. 3.
    Nakasu S, Nakasu Y, Nakajima M, Yokoyama M, Matsuda M, Handa J (1996) Potential doubling time and tumour doubling time in meningiomas and neurinomas. Acta Neurochir (Wien) 138:763–770CrossRefGoogle Scholar
  4. 4.
    Abe M, Kawase T, Urano M, Mizoguchi Y, Kuroda M, Kasahara M, Suzuki H, Kanno T (2000) Analyses of proliferative potential in schwannomas. Brain Tumor Pathol 17:35–40PubMedCrossRefGoogle Scholar
  5. 5.
    Welling DB, Lasak JM, Akhmametyeva E, Ghaheri B, Chang LS (2002) cDNA microarray analysis of vestibular schwannomas. Otol Neurotol 23:736–748PubMedCrossRefGoogle Scholar
  6. 6.
    Saito K, Kato M, Susaki N, Nagatani T, Nagasaka T, Yoshida J (2003) Expression of Ki-67 antigen and vascular endothelial growth factor in sporadic and neurofibromatosis type 2-associated schwannomas. Clin Neuropathol 22:30–34PubMedGoogle Scholar
  7. 7.
    Caye-Thomasen P, Werther K, Nalla A, Bog-Hansen TC, Nielsen HJ, Stangerup SE, Thomsen J (2005) VEGF and VEGF receptor-1 concentration in vestibular schwannoma homogenates correlates to tumor growth rate. Otol Neurotol 26:98–101PubMedCrossRefGoogle Scholar
  8. 8.
    Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676PubMedCrossRefGoogle Scholar
  9. 9.
    Schratzberger P, Schratzberger G, Silver M, Curry C, Kearney M, Magner M, Alroy J, Adelman LS, Weinberg DH, Ropper AH, Isner JM (2000) Favorable effect of VEGF gene transfer on ischemic peripheral neuropathy. Nat Med 6:405–413PubMedCrossRefGoogle Scholar
  10. 10.
    Samoto K, Ikezaki K, Ono M, Shono T, Kohno K, Kuwano M, Fukui M (1995) Expression of vascular endothelial growth factor and its possible relation with neovascularization in human brain tumors. Cancer Res 55:1189–1193PubMedGoogle Scholar
  11. 11.
    Nishikawa R, Cheng SY, Nagashima R, Huang HJ, Cavenee WK, Matsutani M (1998) Expression of vascular endothelial growth factor in human brain tumors. Acta Neuropathol (Berl) 96:453–462CrossRefGoogle Scholar
  12. 12.
    Caye-Thomasen P, Baandrup L, Jacobsen GK, Thomsen J, Stangerup SE (2003) Immunohistochemical demonstration of vascular endothelial growth factor in vestibular schwannomas correlates to tumor growth rate. Laryngoscope 113:2129–2134PubMedCrossRefGoogle Scholar
  13. 13.
    Huang H, Held-Feindt J, Buhl R, Mehdorn HM, Mentlein R (2005) Expression of VEGF and its receptors in different brain tumors. Neurol Res 27:371–377PubMedCrossRefGoogle Scholar
  14. 14.
    Parliament MB, Allalunis-Turner MJ, Franko AJ, Olive PL, Mandyam R, Santos C, Wolokoff B (2000) Vascular endothelial growth factor expression is independent of hypoxia in human malignant glioma spheroids and tumours. Br J Cancer 82:635–641PubMedCrossRefGoogle Scholar
  15. 15.
    Stefanik DF, Fellows WK, Rizkalla LR, Rizkalla WM, Stefanik PP, Deleo AB, Welch WC (2001) Monoclonal antibodies to vascular endothelial growth factor (VEGF) and the VEGF receptor; FLT-1, inhibit the growth of C6 glioma in a mouse xenograft. J Neurooncol 55:91–100PubMedCrossRefGoogle Scholar
  16. 16.
    Brieger J, Bedavanija A, Lehr HA, Maurer J, Mann WJ (2003) Expression of angiogenic growth factors in acoustic neurinoma. Acta Otolaryngol 123:1040–1045PubMedCrossRefGoogle Scholar
  17. 17.
    Pollock BE, Lunsford LD, Kondziolka D, Sekula R, Subach BR, Foote RL, Flickinger JC (1998) Vestibular schwannoma management. Part II. Failed radiosurgery and the role of delayed microsurgery. J Neurosurg 89:949–955PubMedCrossRefGoogle Scholar
  18. 18.
    Hanabusa K, Morikawa A, Murata T, Taki W (2001) Acoustic neuroma with malignant transformation. Case report. J Neurosurg 95:518–521PubMedCrossRefGoogle Scholar
  19. 19.
    Shin M, Ueki K, Kurita H, Kirino T (2002) Malignant transformation of a vestibular schwannoma after gamma knife radiosurgery. Lancet 360:309–310PubMedCrossRefGoogle Scholar
  20. 20.
    Hovinga KE, Stalpers LJ, van Bree C, Donker M, Verhoeff JJ, Rodermond HM, Bosch DA, van Furth WR (2005) Radiation-enhanced vascular endothelial growth factor (VEGF) secretion in glioblastoma multiforme cell lines—a clue to radioresistance? J Neurooncol 74:99–103PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Toshio Uesaka
    • 1
  • Tadahisa Shono
    • 1
  • Satoshi O. Suzuki
    • 2
  • Akira Nakamizo
    • 4
  • Hiroaki Niiro
    • 3
  • Masahiro Mizoguchi
    • 1
  • Toru Iwaki
    • 2
  • Tomio Sasaki
    • 1
  1. 1.Department of Neurosurgery, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Neuropathlogy, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  3. 3.Center for Cellular and Molecular MedicineKyushu University HospitalFukuokaJapan
  4. 4.Department of Neurosurgery, National Hospital OrganizationKyushu Medical CenterFukuokaJapan

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