Brain Tumor Pathology

, Volume 21, Issue 3, pp 117–120 | Cite as

Immunohistochemical analysis of SOX6 expression in human brain tumors

  • Ryo Ueda
  • Kazunari Yoshida
  • Yutaka Kawakami
  • Takeshi Kawase
  • Masahiro Toda
Original Article


We previously demonstrated that the developmentally regulated gene,SOX6, is strongly expressed in glioma cells and in the fetal brain, but only faintly in the normal adult brain. Recent studies have indicated that brain tumor cells may share antigens, signaling systems, and behavior with neural stem/progenitor cells. To test the validity of this proposition, we analyzed the expression of SOX6 in various human central nervous system (CNS) tumors. Immunohistochemical analysis revealed that astrocytic and oligodendroglial tumors expressed SOX6; neuronal-glial cell tumors (central neurocytoma) and embryonal tumors (medulloblastoma), which arise from multipotential stem cell precursors, also showed a high intensity of SOX6 staining. In contrast, ependymal tumors (ependymoma and subependymoma), meningioma, and schwannoma, which are all well differentiated tumors, showed either no staining or only faint staining for SOX6. These results suggest that SOX6 may be expressed in bipotential or multipotential cells capable of neuronal and glial differentiation, but not in fully differentiated cells. SOX6 may be a useful marker for the diagnosis of tumors arising from immature bipotential cells that may differentiate into neuronal and glial cells.

Key words

SOX6 Brain tumor Undifferentiated cell Neural stem/progenitor cell 


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  1. 1.
    Holland EC (2001) Progenitor cells and glioma formation. Curr Opin Neurol 14:683–688PubMedCrossRefGoogle Scholar
  2. 2.
    Dai C, Celestino JC, Okada Y, et al (2001) PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. Genes Dev 15:1913–1925PubMedCrossRefGoogle Scholar
  3. 3.
    Fults D, Pedone C, Dai C, et al (2002) MYC expression promotes the proliferation of neural progenitor cells in culture and in vivo. Neoplasia 4:32–39PubMedCrossRefGoogle Scholar
  4. 4.
    Holland EC, Celestino J, Dai C, et al (2000) Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. Nat Genet 25:55–57PubMedCrossRefGoogle Scholar
  5. 5.
    Dahlstrand J, Collins VP, Lendahl U (1992) Expression of the class VI intermediate filament nestin in human central nervous system tumors. Cancer Res 52:5334–5341PubMedGoogle Scholar
  6. 6.
    Tohyama T, Lee VM, Rorke LB, et al (1992) Nestin expression in embryonic human neuroepithelium and in human neuroepithelial tumor cells. Lab Invest 66:303–313PubMedGoogle Scholar
  7. 7.
    Ueda R, Iizuka Y, Yoshida K, et al (2004) Identification of a human glioma antigen, SOX6, recognized by patients' sera. Oncogene 23:1420–1427PubMedCrossRefGoogle Scholar
  8. 8.
    Ueda R, Yoshida K, Kawakami Y, et al (2004) Expression of a transcriptional factor, SOX6, in human gliomas. Brain Tumor Pathol 21:35–38PubMedCrossRefGoogle Scholar
  9. 9.
    Connor F, Wright E, Denny P, et al (1995) The Sry-related HMG box-containing gene Sox6 is expressed in the adult testis and developing nervous system of the mouse. Nucleic Acids Res 23:3365–3372PubMedGoogle Scholar
  10. 10.
    Hemmati HD, Nakano I, Lazareff JA, et al (2003) Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci U S A 100:15178–15183PubMedCrossRefGoogle Scholar
  11. 11.
    Ignatova TN, Kukekov VG, Laywell ED, et al (2002) Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Glia 39:193–206PubMedCrossRefGoogle Scholar
  12. 12.
    Leung C, Lingbeek M, Shakhova O, et al (2004) Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature 428:337–341PubMedCrossRefGoogle Scholar
  13. 13.
    Toda M, Iizuka Y, Yu W, et al (2001) Expression of the neural RNA-binding protein Musashi1 in human gliomas. Glia 34:1–7PubMedCrossRefGoogle Scholar
  14. 14.
    Kleihues P, Louis DN, Scheithauer BW, et al (2002) The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 61:215–225PubMedGoogle Scholar
  15. 15.
    Rao G, Pedone CA, Coffin CM, et al (2003) c-Myc enhances sonic hedgehog-induced medulloblastoma formation from nestin-expressing neural progenitors in mice. Neoplasia 5:198–204PubMedGoogle Scholar
  16. 16.
    Laudet V, Stehelin D, Clevers H (1993) Ancestry and diversity of the HMG box superfamily. Nucleic Acids Res 21:2493–2501PubMedGoogle Scholar
  17. 17.
    Prior HM, Walter MA (1996) SOX genes: architects of developmen. Mol Med 2:405–412PubMedGoogle Scholar
  18. 18.
    Wegner M (1999) From head to toes: the multiple facets of Sox proteins. Nucleic Acids Res 27:1409–1420PubMedCrossRefGoogle Scholar
  19. 19.
    Dyer MA (2004) Mouse models of childhood cancer of the nervous system. J Clin Pathol 57:561–576PubMedCrossRefGoogle Scholar
  20. 20.
    Mendelsohn G, Maksem JA (1986) Divergent differentiation in neoplasms. Pathologic, biologic, and clinical considerations. Pathol Annu 21(Pt 1):91–119PubMedGoogle Scholar
  21. 21.
    Valdueza JM, Westphal M, Vortmeyer A, et al (1996) Central neurocytoma: clinical, immunohistologic, and biologic findings of a human neuroglial progenitor tumor. Surg Neurol 45:49–56PubMedCrossRefGoogle Scholar
  22. 22.
    von Deimling A, Kleihues P, Saremaslani P, et al (1991) Histogenesis and differentiation potential of central neurocytomas. Lab Invest 64:585–591Google Scholar

Copyright information

© The Japan Society of Brain Tumor Pathology 2004

Authors and Affiliations

  • Ryo Ueda
    • 1
  • Kazunari Yoshida
    • 2
  • Yutaka Kawakami
    • 3
  • Takeshi Kawase
    • 2
  • Masahiro Toda
    • 2
    • 1
  1. 1.Neuroimmunology Research GroupKeio University School of MedicineTokyoJapan
  2. 2.Department of NeurosurgeryKeio University School of MedicineTokyoJapan
  3. 3.Division of Cellular Signaling, Institute for Advanced Medical ResearchKeio University School of MedicineTokyoJapan

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