Skip to main content
Log in

Immunohistochemical analysis of GFAP-δ and nestin in cerebral astrocytomas

  • Original Article
  • Published:
Brain Tumor Pathology Aims and scope Submit manuscript

Abstract

GFAP-δ, the delta isoform of the glial fibrillary acidic protein, is particularly expressed in the subventricular zone (SVZ) of the brain. GFAP-δ positive cells in the SVZ co-express the neural stem cells (NSCs) marker nestin. According to the theory of glioma oncogenesis, transformation of a cell population with stem features which resides in the SVZ could be the origin of astrocytomas. Moreover, it is known that cancer stem cells promote tumor invasion in cerebral astrocytomas. Therefore, we investigated the immunostaining of GFAP-δ and nestin in cerebral astrocytomas and evaluated the correlation between the positive cell ratio of these markers and the neuroimaging features associated with tumor invasion in forty-four cases of grade II, III and IV cerebral astrocytomas (World Health Organization’s classification). Tissue samples were obtained by stereotactic biopsies in all cases. According to the preoperative neuroimaging criteria, tumors were categorized into highly invasive and low invasive. Most of the low-grade and high-grade astrocytomas express GFAP-δ and nestin. The positive cell ratio of GFAP-δ and the positive cell ratio of nestin were statistically significantly higher in highly invasive tumors compared with low-invasive tumors (p < 0.05). Altogether, these results suggest that GFAP-δ and nestin could be clinically relevant markers associated with tumor invasiveness in cerebral astrocytomas.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Jacque CM, Vinner C, Kujas M, Raoul M, Racadot J, Baumann NA (1978) Determination of glial fibrillary acidic protein (GFAP) in human brain tumors. J Neurol Sci 35(1):147–155

    Article  CAS  PubMed  Google Scholar 

  2. Blechingberg J, Holm IE, Nielsen KB, Jensen TH, Jorgensen AL, Nielsen AL (2007) Identification and characterization of GFAPkappa, a novel glial fibrillary acidic protein isoform. Glia 55:497–507

    Article  PubMed  Google Scholar 

  3. Feinstein DL, Weinmaster GA, Milner RJ (1992) Isolation of cDNA clones encoding rat glial fibrillary acidic protein: expression in astrocytes and in Schwann cells. J Neurosci Res 32:1–14

    Article  CAS  PubMed  Google Scholar 

  4. Zelenika D, Grima B, Brenner M, Pessac B (1995) A novel glial fibrillary acidic protein mRNA lacking exon 1. Brain Res Mol Brain Res 30:251–258

    Article  CAS  PubMed  Google Scholar 

  5. 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(4):289–300

    Article  PubMed  Google Scholar 

  6. Van den Berge SA, Middeldorp J, Zhang CE, Curtis MA, Leonard BW, Mastroeni D, Voorn P, van de Berg WD, Huitinga I, Hol EM (2010) Longterm quiescent cells in the aged human subventricular neurogenic system specifically express GFAP-delta. Aging Cell 9(3):313–326

    Article  PubMed  Google Scholar 

  7. Sanai N, Tramontin AD, Quiñones-Hinojosa A, Barbaro NM, Gupta N, Kunwar S, Lawton MT, McDermott MW, Parsa AT, Manuel-García Verdugo J, Berger MS, Alvarez-Buylla A (2004) Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427:740–744

    Article  CAS  PubMed  Google Scholar 

  8. Sanai N, Alvarez-Buylla A, Berger MS (2005) Neural stem cells and the origin of gliomas. N Engl J Med 353:811–822

    Article  CAS  PubMed  Google Scholar 

  9. 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(4):394–405

    Article  CAS  PubMed  Google Scholar 

  10. Bleau AM, Howard BM, Taylor LA, Gursel D, Greenfield JP, Lim Tung HY, Holland EC, Boockvar JA (2008) New strategy for the analysis of phenotypic marker antigens in brain tumor-derived neurospheres in mice and humans. Neurosurg Focus 24:E28

    Article  PubMed  Google Scholar 

  11. Dell’Albani P (2008) Stem cell markers in gliomas. Neurochem Res 33:2407–2415

    Article  PubMed  Google Scholar 

  12. Zhang M, Song T, Yang L, Chen R, Wu L, Yang Z, Fang J (2008) Nestin and CD133: valuable stem cell-specific markers for determining clinical outcome of glioma patients. J Exp Clin Cancer Res 24(27):85

    Article  Google Scholar 

  13. CBTRUS (2011) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2004–2007. Source: Central Brain Tumor Registry of the United States, Hinsdale, IL. http://www.cbtrus.org

  14. Farin A, Suzuki SO, Weiker M, Goldman JE, Bruce JN, Canoll P (2006) Transplanted glioma cells migrate and proliferate on host brain vasculature: a dynamic analysis. Glia 53:799–808

    Article  PubMed  Google Scholar 

  15. Andreiuolo F, Junier M-P, Hol EM, Miquel C, Chimelli L, Leonard N, Chneiweiss H, Daumas-Duport C, Varlet P (2009) GFAP-δ immunostaining improves visualization of normal and pathologic astrocytic heterogeneity. Neuropathology 29:31–39

    Article  PubMed  Google Scholar 

  16. Choia K-C, Kwakb S-E, Kimb J-E, Sheen SH, Kang TC (2009) Enhanced glial fibrillary acidic protein-δ expression in human astrocytic tumor. Neurosci Lett 463:182–187

    Article  Google Scholar 

  17. Heo DH, Kim SH, Yang KM, Cho YJ, Kim KN, Yoon do H, Kang TC (2012) A histopathological diagnostic marker for human spinal astrocytoma: expression of glial fibrillary acidic protein-δ. J Neurooncol 108(1):45–52

    Article  CAS  PubMed  Google Scholar 

  18. Beadle C, Assanah MC, Monzo P, Vallee R, Rosenfeld SS, Canoll P (2008) The role of myosin II in glioma invasion of the brain. Mol Biol Cell 19:3357–3368

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Ivkovic S, Beadle C, Noticewala S, Massey SC, Swanson KR, Toro LN, Bresnick AR, Canoll P, Rosenfeld SS (2012) Direct inhibition of myosin II effectively blocks glioma invasion in the presence of multiple motogen. Mol Biol Cell 23(4):533–542

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Brehar FM, Ciurea AV, Zarnescu O, Bleotu C, Gorgan RM, Dragu D, Matei L (2010) Infiltrating growing pattern xenografts induced by glioblastoma and anaplastic astrocytoma derived tumor stem cells. Chirurgia (Bucur) 105(5):685–694

    CAS  Google Scholar 

  21. Zarnescu O, Brehar FM, Bleotu C, Gorgan RM (2011) Co-localization of PCNA, VCAM-1 and caspase-3 with nestin in xenografts derived from human anaplastic astrocytoma and glioblastoma multiforme tumor spheres. Micron 42(8):793–800

    Article  CAS  PubMed  Google Scholar 

  22. Greenberg Mark S (2010) Handbook of neurosurgery, 7th edn. Thieme Medical Publisher, New York

    Google Scholar 

  23. Kleihues Paul, Cavenee Webster (2000) Pathology and genetics of tumors of the nervous system, World Health Organization (WHO) classification of tumors. IARC Press, Lyon

    Google Scholar 

  24. Scarabino T, Giannatempo GM, Nemore F, Popolizio T, Stranieri A (2005) Supratentorial low-grade gliomas. Neuroradiology. J Neurosurg Sci 49(3):73–76

    CAS  PubMed  Google Scholar 

  25. Kitai R, Horita R, Sato K, Yoshida K, Arishima H, Higashino Y, Hashimoto N, Takeuchi H, Kubota T, Kikuta K-I (2010) Nestin expression in astrocytic tumors delineates tumor infiltration. Brain Tumor Pathol 27(1):17–21

    Article  CAS  PubMed  Google Scholar 

  26. Strojnik T, Rosland GV, Sakariassen PO, Kavalar R, Lah T (2007) Neural stem cell markers, nestin and musashi proteins, in the progression of human glioma: correlation of nestin with prognosis of patient survival. Surg Neurol 68:133–143

    Article  PubMed  Google Scholar 

  27. Louis David N, Ohgaki Hiroko, Wiestler Otmar D, Cavenee Webster K, Burger Peter C, Jouvet Anne, Scheithauer Bernd W, Kleihues Paul (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Grant No. 28487/30.10.2012 of “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania (FM Brehar, D Arsene) and grant PN-II-RU-TE-2012-3-0235 of the Romanian National Authority for Scientific Research, CNCS-UEFISCDI (FM Brehar, MRGorgan). We thank Diana M. Branduse, PhD, State University of New York at Binghamton, for her kind support in writing the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Felix Mircea Brehar.

Additional information

F. M. Brehar and D. Arsene equally contributed to the research and manuscript preparation.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Brehar, F.M., Arsene, D., Brinduse, L.A. et al. Immunohistochemical analysis of GFAP-δ and nestin in cerebral astrocytomas. Brain Tumor Pathol 32, 90–98 (2015). https://doi.org/10.1007/s10014-014-0199-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10014-014-0199-8

Keywords

Navigation