Journal of Neuro-Oncology

, Volume 108, Issue 1, pp 45–52 | Cite as

A histopathological diagnostic marker for human spinal astrocytoma: expression of glial fibrillary acidic protein-δ

  • Dong Hwa Heo
  • Se Hoon Kim
  • Kyung-Moo Yang
  • Yong Jun Cho
  • Keung Nyun Kim
  • Do Heum Yoon
  • Tae-Cheon KangEmail author
Laboratory Investigation


Although histopathological diagnosis of spinal cord astrocytomas is important for postoperative treatment planning and prognosis, there is a lack of reliable immunohistochemical markers. The purpose of our study was to assess the expression pattern of GFAP-δ in spinal cord astrocytomas in human patients and to evaluate the utility of GFAP-δ as an immunohistochemical diagnostic marker. A total of 22 patients with spinal cord astrocytic tumors were included in this study. Patients were classified according to the WHO designation of human astrocytic tumors; three patients had grade 1 astrocytomas, 14 had grade 2, and five had Grade 3. Normal control spinal cord tissues were obtained at autopsy from the cervical spinal cords of ten patients with no history of cervical trauma or neurological disease. We evaluated BRAF, IDH1, GFAP, and GFAP-δ immunoreactivity in control tissues and astrocytomas. In normal control tissues, GFAP immunoreactivity was detected in astrocytes whereas GFAP-δ immunoreactivity was observed in very few astrocytes adjacent to the subpial layer of the spinal cord. GFAP-δ immunoreactivity was significantly correlated with spinal cord astrocytoma grade in astrocytomas compared to that in normal control tissues. The optical density of GFAP-δ increased significantly with astrocytoma grade (correlation coefficient, R 2 = 0.680). Also, BRAF and IDH1 immunoreactivity were detected in astrocytoma. We suggest that GFAP-δ may be an additional, reliable histopathological diagnostic marker for spinal cord astrocytomas.


Astrocytic tumor Astrocyte Glial fibrillary acidic protein-δ Spinal cord 



Human glial fibrillary acidic protein-delta


Human v-raf murine sarcoma viral oncogene homolog B1 gene


Human cytosolic NADP+ dependent isocitrate dehydrogenase 1


World Health Organization


Phosphate-buffered saline


Amino acid



This study was supported by the BioGreen21 Program (200810FTH010103002 and 200810FTH010102001) of the Rural Development Administration.

Conflict of interest



  1. 1.
    Henson JW (2001) Spinal cord gliomas. Curr Opin Neurol 14:679–682PubMedCrossRefGoogle Scholar
  2. 2.
    Minehan KJ, Brown PD, Scheithauer BW, Krauss WE, Wright MP (2009) Prognosis and treatment of spinal cord astrocytoma. Inter J Radiat Oncol Biol Phys 73:727–733CrossRefGoogle Scholar
  3. 3.
    Benes V, Barsa P, Suchomel P (2009) Prognostic factors in intramedullary astrocytomas: a literature review. Eur Spine J 18:1397–1422PubMedCrossRefGoogle Scholar
  4. 4.
    Garcs-Ambrossi GL, McGirt MJ, Mehta VA, Sciubba DM, Witham TF, Bydon A, Wolinksy J, Jallo GI, Gokaslan ZL (2009) Factors associated with progression-free survival and long-term neurological outcome after resection of intramedullary spinal cord tumors: analysis of 101 consecutive cases. J Neurosurg Spine 11:591–599CrossRefGoogle Scholar
  5. 5.
    Nakamura M, Shimada K, Ishida E, Nakase H, Konishi N (2007) Genetic analysis to complement histopathological diagnosis of brain tumors. Histol Histopathol 22:327–335PubMedGoogle Scholar
  6. 6.
    Choi K, Kwak S, Kim J, Sheen SH, Kang T (2009) Enhanced glial fibrillary acidic protein-delta expression in human astrocytic tumor. Neuroscie Lett 463:182–187CrossRefGoogle Scholar
  7. 7.
    Figarella Branger D, Maues de Paula A, Colin C, Bouvier C (2011) Histomolecular classification of adult diffuse gliomas: the diagnostic value of immunohistochemical markers. Rev Neurol 167:683–690PubMedCrossRefGoogle Scholar
  8. 8.
    von Deimling A, Korshunov A, Hartmann C (2011) The next generation of glioma biomarkers: MGMT methylation, BRAF fusions and IDH1 mutations. Brain Pathol 21:74–87CrossRefGoogle Scholar
  9. 9.
    Hol EM, Roelofs RF, Moraal E, Sonnemans MAF, Sluijs JA, Proper EA, de Graan PNE, Fischer DF, van Leeuwen FW (2003) Neuronal expression of GFAP in patients with Alzheimer pathology and identification of novel GFAP splice forms. Mol Psychiatry 8:786–796PubMedCrossRefGoogle Scholar
  10. 10.
    Roelofs RF, Fischer DF, Houtman SH, Sluijs JA, Van Haren W, Van Leeuwen FW, Hol EM (2005) Adult human subventricular, subgranular, and subpial zones contain astrocytes with a specialized intermediate filament cytoskeleton. Glia 52:289–300PubMedCrossRefGoogle Scholar
  11. 11.
    Perng M, Wen S, Gibbon T, Middeldorp J, Sluijs J, Hol EM, Quinlan RA (2008) Glial fibrillary acidic protein filaments can tolerate the incorporation of assembly-compromised GFAP-delta, but with consequences for filament organization and alphaB-crystallin association. Mol Biol of Cell 19:4521–4533CrossRefGoogle Scholar
  12. 12.
    Yang P, Baker KA, Hagg T (2005) A disintegrin and metalloprotease 21 (ADAM21) is associated with neurogenesis and axonal growth in developing and adult rodent CNS. J Comp Neurol 490:163–179PubMedCrossRefGoogle Scholar
  13. 13.
    Constantini S, Houten J, Miller DC, Freed D, Ozek MM, Rorke LB, Allen JC, Epstein FJ (1996) Intramedullary spinal cord tumors in children under the age of 3 years. J Neurosurg 85:1036–1043PubMedCrossRefGoogle Scholar
  14. 14.
    McComb RD, Burger PC (1985) Pathologic analysis of primary brain tumors. Neurol Clin 3:711–728PubMedGoogle Scholar
  15. 15.
    Korshunov A, Meyer J, Capper D, Christians A, Remke M, Witt H, Pfister S, von Deimling A, Hartmann C (2009) Combined molecular analysis of BRAF and IDH1 distinguishes pilocytic astrocytoma from diffuse astrocytoma. Acta Neuropathol 118:401–405PubMedCrossRefGoogle Scholar
  16. 16.
    Martinian L, Boer K, Middeldorp J, Hol EM, Sisodiya SM, Squier W, Aronica E, Thom M (2009) Expression patterns of glial fibrillary acidic protein (GFAP)-delta in epilepsy-associated lesional pathologies. Neuropathol Appl Neurobiol 35:394–405PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Dong Hwa Heo
    • 6
  • Se Hoon Kim
    • 1
  • Kyung-Moo Yang
    • 2
  • Yong Jun Cho
    • 6
  • Keung Nyun Kim
    • 3
  • Do Heum Yoon
    • 3
  • Tae-Cheon Kang
    • 4
    • 5
    Email author
  1. 1.Department of Pathology, College of MedicineYonsei UniversitySeoulKorea
  2. 2.Department of Forensic MedicineNational Forensic ServiceSeoulKorea
  3. 3.Department of Neurosurgery, College of MedicineSeverance Hospital, Yonsei UniversitySeoulKorea
  4. 4.Department of Anatomy & Neurobiology, College of MedicineHallym UniversityChuncheonKorea
  5. 5.Institute of Epilepsy Research, College of MedicineHallym UniversityChuncheonKorea
  6. 6.Department of Neurosurgery, College of MedicineChuncheon Sacred Heart Hospital, Hallym UniversityChuncheonKorea

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