Journal of Neuro-Oncology

, Volume 77, Issue 2, pp 153–159 | Cite as

Survivin expression in ganglioglioma

  • Audrey Rousseau
  • Michèle Kujas
  • Anne-Marie Bergemer-Fouquet
  • Rémy van Effenterre
  • Jean-Jacques Hauw
Laboratory Investigation


Gangliogliomas are unusual central nervous system (CNS) neoplasms occurring mainly in children and young adults and inducing chronic pharmacoresistant epilepsy. These are usually well differentiated neuroepithelial tumors composed of neurons in association with neoplastic glial cells. Gangliogliomas present with favorable outcome. However, some may recur and/or progress to anaplasia and be associated with a dismal prognosis. Since histopathological features do not consistently correlate with clinical outcome, reliable prognostic factors have yet to be defined in gangliogliomas. Survivin is an anti-apoptotic protein whose expression has been found to be of prognostic significance in many human cancers, including gliomas. The objective of this study was to assess survivin expression using immunohistochemistry in 15 gangliogliomas. Ten lesions were low-grade neoplasms whereas 5 were high-grade tumors. Survivin expression appeared restricted to the neoplastic glial component and was detected in 6/15 gangliogliomas. Two additional tumors expressed survivin upon relapse. Half survivin expressing lesions displayed less than 1% immunoreactive cells. Survivin expression in more than 5% neoplastic glial cells was detected only in malignant and/or recurrent gangliogliomas. Extended lifespan in survivin expressing cells might enhance aggressive behavior in these tumors through accumulation of mutations, thereby allowing progression to malignant phenotypes. Survivin expression may carry a negative prognostic value in gangliogliomas.


apoptosis brain tumor central nervous system ganglioglioma glioneuronal tumor immunohistochemistry prognosis survivin 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lantos PL, Louis DN, Rosenblum MK, Kleihues P: Tumours of the nervous system In: Graham DI, Lantos PL, (eds) Greenfield’s Neuropathology. Arnold, London 2002, pp. 767–980Google Scholar
  2. 2.
    Nelson JS, Bruner JM, Wiestler OD, Vandenberg SR, 2000 Ganglioglioma and gangliocytoma In: Kleihues P, Cavenee WK, (eds) Pathology and Genetics of Tumours of the Nervous System. World Health Organization Classification of TumoursIARC, Lyon, 96–98Google Scholar
  3. 3.
    Im SH, Chung CK, Cho BK, Lee SK, 2002 Supratentorial ganglioglioma and epilepsy: postoperative seizure outcome J Neurooncol 57: 59–66PubMedCrossRefGoogle Scholar
  4. 4.
    Blümcke I, Wiestler OD, 2002 Gangliogliomas: an intriguing tumor entity associated with focal epilepsies J Neuropathol Exp Neurol 61:575–584PubMedGoogle Scholar
  5. 5.
    Prayson RA, Khajavi K, Comair YG, 1995 Cortical architectural abnormalities and MIB1 immunoreactivity in gangliogliomas: a study of 60 patients with intracranial tumors J Neuropathol Exp Neurol 54:513–520PubMedCrossRefGoogle Scholar
  6. 6.
    Wolf HK, Müller MB, Spänle M, Zentner J, Schramm J, Wiestler OD, 1994 Gangliogliomas: a detailed histopathological and immunohistochemical analysis of 61 cases Acta Neuropathol 88: 166–173PubMedGoogle Scholar
  7. 7.
    Im SH, Chung CK, Cho BK, Wang KC, Yu IK, Song IC, Cheon GJ, Lee DS, Kim NR, Chi JG, 2002 Intracranial ganglioglioma: preoperative characteristics and oncologic outcome after surgeryJ Neurooncol 59: 173–183PubMedCrossRefGoogle Scholar
  8. 8.
    Zentner J, Wolf HK, Ostertun B, Hufnagel A, Campos MG, Solymosi L, Schramm J, 1994 Gangliogliomas: clinical, radiological, and histopathological findings in 51 patients J Neurol Neurosurg Psychiatry 57: 1497–1502PubMedGoogle Scholar
  9. 9.
    Prayson RA, Estes ML, Morris HH, 1993 Coexistence of neoplasia and cortical dysplasia in patients presenting with seizuresEpilepsia 34: 609–615PubMedCrossRefGoogle Scholar
  10. 10.
    Mickle JP, 1992 Ganglioglioma in children: a review of 32 cases at the University of FloridaPediatr Neurosurg 18: 310–314PubMedGoogle Scholar
  11. 11.
    Zhu JJ, Leon SP, Folkerth RD, Guo SZ, Wu JK, Black PM, 1997 Evidence for clonal origin of neoplastic neuronal and glial cells in gangliogliomasAm J Pathol 151: 565–571PubMedGoogle Scholar
  12. 12.
    Hakim R, Loeffler JS, Anthony DC, Black PM, 1997 Gangliogliomas in adults Cancer 79: 127–131PubMedCrossRefGoogle Scholar
  13. 13.
    Selch M, Goy BW, Lee SP, El-Sadin S, Kincaid P, Park SH, Withers HR, 1998 Gangliogliomas. Experience with 34 patients and review of the literatureAm J Clin Oncol 21: 557–564PubMedCrossRefGoogle Scholar
  14. 14.
    Hirose T, Scheithauer BW, Gerber HA, Altermatt HJ, Vandenberg SR, 1997 Ganglioglioma. An ultrastructural and immunohistochemical studyCancer 79: 989–1003PubMedCrossRefGoogle Scholar
  15. 15.
    Rumana CS, Valadka AB, 1998 Radiation therapy and malignant degeneration of benign supratentorial gangliogliomasNeurosurg 42: 1038–1043CrossRefGoogle Scholar
  16. 16.
    Sasaki A, Hirato J, Nakazato Y, Tamura M, Kadowaki H, 1996 Recurrent anaplastic ganglioglioma: pathological characterization of tumor cellsJ Neurosurg 84: 1055–1059PubMedGoogle Scholar
  17. 17.
    Danjoux M, Sabatier J, Uro-Coste E, Roche H, Delisle M-B, 2001 Gangliogliome anaplasique temporal avec métastases médullairesAnn Pathol 21: 55–58PubMedGoogle Scholar
  18. 18.
    Hayashi Y, Iwato M, Hasegawa M, Tachibana O, von Deimling A, Yamashita J, 2001 Malignant transformation of a gangliocytoma/ganglioglioma into a glioblastoma multiforme: a molecular genetic analysis J Neurosurg 95: 138–142PubMedGoogle Scholar
  19. 19.
    Miller DC, Lang FF, Epstein FJ, 1993 Central nervous system gangliogliomas. Part 1: Pathology J Neurosurg 79: 859–866PubMedGoogle Scholar
  20. 20.
    Wacker MR, Cogen PH, Etzell E, Daneshvar L, Davis RL, Prados MD, 1992 Diffuse leptomeningeal involvement by a ganglioglioma in a childJ Neurosurg 77: 302–306PubMedGoogle Scholar
  21. 21.
    Lang FF, Epstein FJ, Ransohoff J, Allen JC, Wisoff J, Abbott IR, Miller DC, 1993 Central nervous system gangliogliomas. Part 2: Clinical outcomeJ Neurosurg 79: 867–873PubMedCrossRefGoogle Scholar
  22. 22.
    Luyken C, Blümcke I, Fimmers R, Urbach H, Wiestler OD, Schramm J, 2004 Supratentorial gangliogliomas: histopathologic grading and tumor recurrence in 184 patients with a median follow-up of 8 yearsCancer 101: 146–155PubMedCrossRefGoogle Scholar
  23. 23.
    Monzo M, Rosell R, Felip E, Astudillo J, Sanchez J, Maestre J, Martin C, Font A, Barnadas A, Abad A, 1999 A novel anti-apoptosis gene: re-expression of survivin messenger RNA as a prognosis marker in non-small-cell lung cancersJ Clin Oncol 17: 2100–2104PubMedGoogle Scholar
  24. 24.
    Sarela A, Macadam R, Farmery S, Makham A, Guillou P, 2000 Expression of the antiapoptosis gene, survivin, predicts death from recurrent colorectal carcinomaGut 46: 645–650PubMedCrossRefGoogle Scholar
  25. 25.
    Sarela AI, Scott N, Ramsdale J, Markham AF, Guillou PJ, 2001 Immunohistochemical detection of the anti-apoptosis protein, survivin, predicts survival after curative resection of stage II colorectal carcinomasAnn Surg Oncol 8: 305–310PubMedCrossRefGoogle Scholar
  26. 26.
    Tanaka K, Iwamoto S, Gon G, Nohara T, Iwamoto M, Tanigawa N, 2000 Expression of survivin and its relationship to loss of apoptosis in breast carcinomasClin Cancer Res 6: 127–134PubMedGoogle Scholar
  27. 27.
    Fangusaro JR, Jiang Y, Holloway MP, Caldas H, Singh V, Boué DR, Hayes J, Altura RA, 2005 Survivin, Survivin-2B, and Survivin-deltaEx3 expression in medulloblastoma: biologic markers of tumour morphology and clinical outcomeBr J Cancer 1–7Google Scholar
  28. 28.
    Kajiwara Y, Yamasaki F, Hama S, Yahara K, Yoshioka H, Sugiyama K, Arita K, Kurisu K, 2003 Expression of survivin in astrocytic tumors. Correlation with malignant grade and prognosisCancer 97: 1077–1083PubMedCrossRefGoogle Scholar
  29. 29.
    Chakravarti A, Noll E, Black P McL, Finkelstein DF, Dianne M, Dyson NJ, Loeffler JS, 2002 Quantitatively determined survivin expression levels are of prognostic value in human gliomasJ Clin Oncol 20: 1063–1068PubMedCrossRefGoogle Scholar
  30. 30.
    Caldas H, Jiang Y, Holloway MP, Fangusaro J, Mahotka C, Altura RA, Conway EM, 2005 Survivin splice variants regulate the balance between proliferation and cell death. Oncogene 1–14Google Scholar
  31. 31.
    Ambrosini G, Adida C, Altieri DC, 1997 A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma Nat Med 3: 917–921PubMedCrossRefGoogle Scholar
  32. 32.
    Adida C, Crotty PL, McGrath J, Berrebi D, Diebold J, Altieri DC, 1998 Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiationAm J Pathol 152: 43–49PubMedGoogle Scholar
  33. 33.
    Adida C, Haioun C, Gaulard P, Lepage E, Morel P, Brière J, Dombret H, Reyes F, Diebold J, Gisselbrecht C, Salles G, Altieri DC, Molina TJ, 2000 Prognostic significance of survivin expression in diffuse large B-cell lymphomasBlood 96: 1921–1925PubMedGoogle Scholar
  34. 34.
    Invernizzi R, Travaglino E, Lunghi M, Klersy C, Bernasconi P, Cazzola M, Ascari E, 2004 Survivin expression in acute leukemias and myelodysplastic syndromesLeuk Lymphoma 45: 2229–2237PubMedCrossRefGoogle Scholar
  35. 35.
    Uematsu M, Ohsawa I, Aokage T, Nishimaki K, Matsumoto K, Takahashi H, Asoh S, Teramoto A, Ohta S, 2005 Prognostic significance of the immunohistochemical index of survivin in glioma: a comparative study with the MIB-1 indexJ Neurooncol 72: 231–238PubMedCrossRefGoogle Scholar
  36. 36.
    Chakravarti A, Zhai GG, Zhang M, Malhotra R, Latham DE, Delaney MA, Robe P, Nestler U, Song Q, Loeffler J, 2004 Survivin enhances radiation resistance in primary human glioblastoma cells via caspase-independent mechanismsOncogene 23: 7494–7506PubMedCrossRefGoogle Scholar
  37. 37.
    Asanuma K, Moriai R, Yajima T, Yagihashi A, Yamada M, Kobayashi D, Watanabe N, 2000 Survivin as a radioresistance factor in pancreatic cancerJpn J Cancer Res 91: 1204–1209PubMedGoogle Scholar
  38. 38.
    Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T, Reed JC, 1998 IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugsCancer Res 58: 5315–5320PubMedGoogle Scholar
  39. 39.
    Li F, 2004 Role of survivin and its slice variants in tumorigenesisBr J Cancer 1–5Google Scholar
  40. 40.
    Hassounah M, Lach B, Allam A, Al-Khalaf H, Siddiqui Y, Pangue-Cruz N, Al-Omeir A, Al-Ahdal MN, Aboussekhra A, 2005 Benign tumors from the human nervous system express high levels of survivin and are resistant to spontaneous and radiation-induced apoptosisJ Neurooncol 72: 203–208PubMedCrossRefGoogle Scholar
  41. 41.
    Julien T, Frankel B, Longo S, Kyle M, Gibson S, Shillitoe E, Ryken T, 2000 Antisense-mediated inhibition of the bcl-2 gene induces apoptosis in human malignant gliomaSurg Neurol 53: 360–368PubMedCrossRefGoogle Scholar
  42. 42.
    O’Connor DS, Schechner JS, Adida C, Mesri M, Rothermel AL, Li F, Nath AK, Pober JS, Altieri DC, 2000 Control of apoptosis during angiogenesis by survivin expression in endothelial cellsAm J Pathol 156: 393–398PubMedGoogle Scholar
  43. 43.
    Mesri M, Morales-Ruiz M, Ackermann EJ, Bennett CF, Pober JS, Sessa WC, Altieri DC, 2001 Suppression of vascular endothelial growth factor-mediated endothelial cell protection by survivin targeting. Am J Pathol 158: 1757–1765PubMedGoogle Scholar
  44. 44.
    Altieri DC, 2003 Validating survivin as a cancer therapeutic targetNat Rev Cancer 3: 46–54PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Audrey Rousseau
    • 1
    • 4
  • Michèle Kujas
    • 1
  • Anne-Marie Bergemer-Fouquet
    • 3
  • Rémy van Effenterre
    • 2
  • Jean-Jacques Hauw
    • 1
  1. 1.Raymond Escourolle Neuropathology DepartmentPitié-Salpêtrière HospitalParisFrance
  2. 2.Neurosurgery DepartmentPitié-Salpêtrière HospitalParisFrance
  3. 3.Pathology DepartmentBretonneau HospitalToursFrance
  4. 4.Molecular Pathology Unit, DN LouisCharlestownUSA

Personalised recommendations