Advertisement

Journal of Neuro-Oncology

, Volume 98, Issue 1, pp 49–55 | Cite as

Spontaneous canine gliomas: overexpression of EGFR, PDGFRα and IGFBP2 demonstrated by tissue microarray immunophenotyping

  • Robert J. HigginsEmail author
  • Peter J. Dickinson
  • Richard A. LeCouteur
  • Andrew W. Bollen
  • Huamin Wang
  • Hua Wang
  • Linda J. Corely
  • Lynnette M. Moore
  • Wei Zang
  • Gregory N. Fuller
Laboratory Investigation - Human/Animal Tissue

Abstract

Fifty-seven spontaneous canine gliomas were histologically classified and graded using the latest World Health Organization (WHO 2007) criteria for classification of human gliomas. A total of 19 canine astrocytomas were classified as follows: grade IV (GBM) n = 7; grade III n = 5; and grade II, n = 7. Thirty-eight oligodendrogliomas were classified as either grade III (anaplastic) n = 35 or low grade II n = 3. Tissue microarray (TMA) immunohistochemistry was used to evaluate tumor expression of EGFR, PDGFRa and IGFBP2, three key molecules of known pathophysiological importance in human gliomas. Findings were correlated with tumor classification and grade. Increased EGFR expression was demonstrated in 57% of GBMs, 40% of grade III and 28% of grade II astrocytomas. EGFR expression occurred in only 3% of grade III oligodendrogliomas. Increased expression of PDGFRα was demonstrated in 43% of GBMs, 20% of grade III, and 14% of grade II astrocytomas. In the oligodendroglioma series, 94% of grade III tumors overexpressed PDGFRα. IGFBP2 expression was detected in 71, 60 and 28% of GBMs, grade III and grade II astrocytomas respectively. IGFBP2 expression occurred in 48% of anaplastic and in 33% of low grade oligodendrogliomas. Expression of EGFR, PDGFRα or IGFBP2 was not detected in normal canine CNS control TMA cores. The incidence of overexpression of EGFR, PDGFRα and IGFBP2 in these canine gliomas closely parallels that in human tumors of similar type and grade. These findings support a role for the spontaneous canine glioma model in directed pathway-targeting therapeutic studies.

Keywords

Canine EGFR Glioma IGFBP2 Immunohistochemistry PDGFRα Tissue microarray 

References

  1. 1.
    Kliehues P, Burger PC, Aldape KD (2007) Glioblastoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavanee WK et al (eds) WHO classification of tumours of the central nervous system. IARC, Lyon, France, pp 33–49Google Scholar
  2. 2.
    Fleming TP, Saxena A, Clark WC et al (1992) Amplification or overexpression of platelet derived growth factor receptors and epidermal growth factor receptor in human glial tumors. Cancer Res 52:4550–4553PubMedGoogle Scholar
  3. 3.
    Haberler C, Gelpi E, Marosi C et al (2006) Immunohistochemical analysis of platelet derived growth factor receptor-α,-β, c-kit, c-abl, and arg proteins in glioblastoma: possible implications for patient selection for imatinib mesylate therapy. J Neurooncol 76:105–109CrossRefPubMedGoogle Scholar
  4. 4.
    DiRocco F, Carroll RS, Zhang J, Black PM (1998) Platelet-derived growth factor and its receptor expression in human oligodendrogliomas. Neurosurgery 42:341–346CrossRefGoogle Scholar
  5. 5.
    Smith JS, Wang XY, Jetal Qian (2000) Amplification of the platelet-derived growth factor receptor-A (PDGFA) gene occurs in oligodendrogliomas with grade IV anaplastic features. J Neuropathol Exp Neurol 59:495–503PubMedGoogle Scholar
  6. 6.
    Shih AH, Dai C, Hu X et al (2004) Dose-dependent effects of platelet-derived growth factor-B on glial tumorigenesis. Cancer Res 64:4783–4789CrossRefPubMedGoogle Scholar
  7. 7.
    Fuller GN, Rhee CH, Hess KR et al (1999) Reactivation of insulin-like growth factor binding protein 2 expression in glioblastoma multiforme: a revelation by parallel gene expression profiling. Cancer Res 59:4228–4232PubMedGoogle Scholar
  8. 8.
    Zhang W, Wang H, Song SW, Fuller GN (2002) Insulin-like growth factor binding protein 2: gene expression microarrays and the hypothesis-generation paradigm. Brain Pathol 12:87–94PubMedGoogle Scholar
  9. 9.
    Elmlinger MW, Deininger MH, Schuett BS et al (2001) In vivo expression of insulin-like growth factor-binding protein-2 in human gliomas increases with the tumor grade. Endocrinology 142:1652–1658CrossRefPubMedGoogle Scholar
  10. 10.
    McDonald KL, O’Sullivan MG, Parkinson JF et al (2007) IQGAP1 and IGFBP2: valuable biomarkers for determining prognosis in glioma patients. J Neuropathol Exp Neurol 66:405–417CrossRefPubMedGoogle Scholar
  11. 11.
    Wang H, Wang H, Shen W et al (2003) Insulin-like growth factor binding protein 2 enhances glioblastoma invasion by activating invasion-enhancing genes. Cancer Res 63:4315–4321PubMedGoogle Scholar
  12. 12.
    Wang GK, Hu L, Fuller GN, Zhang W (2006) An interaction between insulin-like growth factor-binding protein 2 (IFGBP2) and integrin α5 is essential for IGFBP2-induced cell mobility. J Biol Chem 281:14085–14091CrossRefPubMedGoogle Scholar
  13. 13.
    Dunlap SM, Celestino J, Wang H et al (2007) Insulin-like growth factor binding protein 2 promotes glioma development and progression. PNAS 104:11736–11741CrossRefPubMedGoogle Scholar
  14. 14.
    Priester WA, Mantel N (1971) Occurrence of tumors in domestic animals. Data from 12 United States and Canadian colleges of veterinary medicine. J Natl Cancer Inst 47:1333–1344PubMedGoogle Scholar
  15. 15.
    Lipsitz D, Higgins RJ, Kortz GD et al (2003) Glioblastoma multiforme: clinical findings, magnetic resonance imaging and pathology in five dogs. Vet Pathol 40:659–669CrossRefPubMedGoogle Scholar
  16. 16.
    Stoica G, Kim H-T, Hall DG, Coates JR (2004) Morphology, immunocytochemistry, and genetic alterations in dog astrocytomas. Vet Pathol 41:10–19CrossRefPubMedGoogle Scholar
  17. 17.
    Dickinson PJ, Roberts B, Higgins RJ et al (2006) Expression of tyrosine kinase receptors VEGF-1 (FLT-1), VEGFR-2 (KDR), EGFR-1, PDGFRα and c-Met in canine brain tumors. Vet Comp Oncol 4:132–140CrossRefPubMedGoogle Scholar
  18. 18.
    Louis DN, Ohgaki H, Wiestler OD et al (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109CrossRefPubMedGoogle Scholar
  19. 19.
    Wang H, Wang H, Zhang W, Fuller GN (2002) Tissue microarrays: applications in neuropathology research, diagnosis and education. Brain Pathol 12:95–107PubMedCrossRefGoogle Scholar
  20. 20.
    Watanabe K, Tachibana O, Sata K, Yonekawa Y, Kliehues P (1996) Ohaki H overexpression of the EF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol 6:217–223CrossRefPubMedGoogle Scholar
  21. 21.
    Li JY, Wang H, May S, Song X, Fueyo J, Fuller GN, Wang H (2008) Constitutive activation of c-Jun N-terminal kinase correlates with histologic grade and EGFR expression in diffuse gliomas. J Neurooncol 88:11–17CrossRefPubMedGoogle Scholar
  22. 22.
    Reifenberger J, Reifenberger G, Ichimura K, Schmidt EE, Wechsler W, Collins VP (1996) Epidermal growth factor receptor expression in oligodendroglial tumors. Am J Pathol 149:29–35PubMedGoogle Scholar
  23. 23.
    McLendon RE, Wikstrand CJ, Matthews MR, Al-Baradei R, Bigner S, Bigner D (2000) Glioma-associated antigen expression in oligodendroglial neoplasms: tenascin and epidermal growth factor receptor. J Histochem Cytochem 48:1103–1110PubMedGoogle Scholar
  24. 24.
    Robinson S, Cohen M, Prayson R, Ransohoff RM, Tabrizi N, Miller RH (2001) Constitutive expression of growth-related oncogene and its receptor in oligodendrogliomas. Neurosurgery 48:864–873CrossRefPubMedGoogle Scholar
  25. 25.
    Dai C, Lyustikman Y, Shih A et al (2005) The characteristics of astrocytomas and oligodendrogliomas are caused by two distinct and interchangeable signaling formats. Neoplasia 7:397–406CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Robert J. Higgins
    • 1
    Email author
  • Peter J. Dickinson
    • 2
  • Richard A. LeCouteur
    • 2
  • Andrew W. Bollen
    • 3
  • Huamin Wang
    • 4
  • Hua Wang
    • 5
  • Linda J. Corely
    • 4
  • Lynnette M. Moore
    • 4
  • Wei Zang
    • 4
  • Gregory N. Fuller
    • 4
  1. 1.Department of Pathology, Microbiology and ImmunologySchool of Veterinary Medicine, University of California DavisDavisUSA
  2. 2.Department of Surgical and Radiological SciencesSchool of Veterinary Medicine, University of California DavisDavisUSA
  3. 3.Department of PathologySchool of Medicine, University of CaliforniaSan FranciscoUSA
  4. 4.Department of PathologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA
  5. 5.Department of GI Medical OncologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA

Personalised recommendations