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Glioblastoma with oligodendroglial component represents a subgroup of glioblastoma with high prevalence of IDH1 mutation and association with younger age

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Abstract

Glioblastoma with an oligodendroglial component (GBMO) is recognized as a subgroup of glioblastoma (GBM); however, the molecular and clinicopathological characteristics of GBMO are obscure. We evaluated the methylation status of MGMT, IDH1/2 mutation, deletions of 1p and 19q and expression of IDH1, p53, p16, CD151, and galectin3 proteins in 42 GBMOs (32 primary and 10 secondary tumors). Our aims were to correlate our molecular findings with clinicopathologic features, and to compare molecular-to-clinical correlations in the 42 GBMOs with the corresponding correlations in 45 GBMs. GBMO was subdivided into two subgroups according to the predominant cell component comprising >50 % of tumors: the astrocytic predominant type (GBMO-A) and oligodendroglioma predominant type (GBMO-O). Methylation of MGMT, IDH1/2 mutation, and co-deletion of 1p and 19q were found in 31.0, 26.2, and 17.9 % of patients with GBMO, respectively. Clinicopathological and molecular characteristics did not differ significantly between GBMO-A and GBMO-O. However, patients with GBMO-O experienced better outcomes than patients with GBMO-A (p = 0.007). On multivariate analysis the predominant cell type was an independent prognostic factor in overall survival [hazard ratio 4.2 (95 % confidence interval 1.4–12.8), p = 0.011]. When compared to patients with classic GBM, those with GBMO were younger (49.21 vs. 57.47, p = 0.003) and more frequently had tumors with IDH1 mutation (23.8 vs. 4.4 %, p = 0.009). Survival was similar in patients with GBMO and with classic GBM. Based on these results, GBMO may represent a subgroup of GBM that is associated with IDH1 mutation and younger age, although similar to classic GBM in prognosis.

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References

  1. Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL, Burkhard C, Schuler D, Probst-Hensch NM, Maiorka PC, Baeza N, Pisani P, Yonekawa Y, Yasargil MG, Lutolf UM, Kleihues P (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64:6892–6899

    Article  PubMed  CAS  Google Scholar 

  2. Ohgaki H, Kleihues P (2005) Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol 64:479–489

    PubMed  CAS  Google Scholar 

  3. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2007) WHO classification of tumours of the central nervous system, 4th edn. International Agency for Research on Cancer, Lyon

    Google Scholar 

  4. Hilton DA, Penney M, Pobereskin L, Sanders H, Love S (2004) Histological indicators of prognosis in glioblastomas: retinoblastoma protein expression and oligodendroglial differentiation indicate improved survival. Histopathology 44:555–560

    Article  PubMed  CAS  Google Scholar 

  5. Kraus JA, Lamszus K, Glesmann N, Beck M, Wolter M, Sabel M, Krex D, Klockgether T, Reifenberger G, Schlegel U (2001) Molecular genetic alterations in glioblastomas with oligodendroglial component. Acta Neuropathol 101:311–320

    PubMed  CAS  Google Scholar 

  6. Salvati M, Formichella AI, D’Elia A, Brogna C, Frati A, Giangaspero F, Delfini R, Santoro A (2009) Cerebral glioblastoma with oligodendrogliomal component: analysis of 36 cases. J Neurooncol 94:129–134

    Article  PubMed  Google Scholar 

  7. Vordermark D, Ruprecht K, Rieckmann P, Roggendorf W, Vince GH, Warmuth-Metz M, Kolbl O, Flentje M (2006) Glioblastoma multiforme with oligodendroglial component (GBMO): favorable outcome after post-operative radiotherapy and chemotherapy with nimustine (ACNU) and teniposide (VM26). BMC Cancer 6:247

    Article  PubMed  Google Scholar 

  8. Wang Y, Li S, Chen L, You G, Bao Z, Yan W, Shi Z, Chen Y, Yao K, Zhang W, Kang C, Jiang T (2012) Glioblastoma with an oligodendroglioma component: distinct clinical behavior, genetic alterations, and outcome. Neuro Oncol 14(4):518–525

    Article  PubMed  Google Scholar 

  9. He J, Mokhtari K, Sanson M, Marie Y, Kujas M, Huguet S, Leuraud P, Capelle L, Delattre JY, Poirier J, Hoang-Xuan K (2001) Glioblastomas with an oligodendroglial component: a pathological and molecular study. J Neuropathol Exp Neurol 60:863–871

    PubMed  CAS  Google Scholar 

  10. Pinto LW, Araujo MB, Vettore AL, Wernersbach L, Leite AC, Chimelli LM, Soares FA (2008) Glioblastomas: correlation between oligodendroglial components, genetic abnormalities, and prognosis. Virchows Arch 452:481–490

    Article  PubMed  Google Scholar 

  11. Klink B, Schlingelhof B, Klink M, Stout-Weider K, Patt S, Schrock E (2011) Glioblastomas with oligodendroglial component-common origin of the different histological parts and genetic subclassification. Cell Oncol (Dordr) 34:261–275

    Article  Google Scholar 

  12. Homma T, Fukushima T, Vaccarella S, Yonekawa Y, Di Patre PL, Franceschi S, Ohgaki H (2006) Correlation among pathology, genotype, and patient outcomes in glioblastoma. J Neuropathol Exp Neurol 65:846–854

    Article  PubMed  CAS  Google Scholar 

  13. Hegi ME, Janzer RC, Lambiv WL, Gorlia T, Kouwenhoven MC, Hartmann C, von Deimling A, Martinet D, Besuchet SN, Diserens AC, Hamou MF, Bady P, Weller M, van den Bent MJ, Mason WP, Mirimanoff RO, Stupp R, Mokhtari K, Wesseling P (2012) Presence of an oligodendroglioma-like component in newly diagnosed glioblastoma identifies a pathogenetically heterogeneous subgroup and lacks prognostic value: central pathology review of the EORTC_26981/NCIC_CE.3 trial. Acta Neuropathol 123(6):841–852

    Article  PubMed  CAS  Google Scholar 

  14. Nakamura H, Makino K, Kuratsu J (2011) Molecular and clinical analysis of glioblastoma with an oligodendroglial component (GBMO). Brain Tumor Pathol 28:185–190

    Article  PubMed  CAS  Google Scholar 

  15. Kwon MJ, Kim ST, Kong DS, Lee D, Park S, Kang SY, Song JY, Nam DH, Kato Y, Choi YL, Suh YL (2012) Mutated IDH1 is a favorable prognostic factor for type 2 gliomatosis cerebri. Brain Pathol 22:307–317

    Article  PubMed  CAS  Google Scholar 

  16. van den Bent MJ, Hegi ME, Stupp R (2006) Recent developments in the use of chemotherapy in brain tumours. Eur J Cancer 42:582–588

    Article  PubMed  Google Scholar 

  17. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773

    Article  PubMed  CAS  Google Scholar 

  18. Neder L, Marie SK, Carlotti CG Jr, Gabbai AA, Rosemberg S, Malheiros SM, Siqueira RP, Oba-Shinjo SM, Uno M, Aguiar PH, Miura F, Chammas R, Colli BO, Silva WA Jr, Zago MA (2004) Galectin-3 as an immunohistochemical tool to distinguish pilocytic astrocytomas from diffuse astrocytomas, and glioblastomas from anaplastic oligodendrogliomas. Brain Pathol 14:399–405

    Article  PubMed  CAS  Google Scholar 

  19. Sanson M, Marie Y, Paris S, Idbaih A, Laffaire J, Ducray F, El Hallani S, Boisselier B, Mokhtari K, Hoang-Xuan K, Delattre JY (2009) Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 27:4150–4154

    Article  PubMed  CAS  Google Scholar 

  20. Hartmann C, Hentschel B, Wick W, Capper D, Felsberg J, Simon M, Westphal M, Schackert G, Meyermann R, Pietsch T, Reifenberger G, Weller M, Loeffler M, von Deimling A (2010) Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. Acta Neuropathol 120:707–718

    Article  PubMed  Google Scholar 

  21. Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, Konermann C, Pfaff E, Tonjes M, Sill M, Bender S, Kool M, Zapatka M, Becker N, Zucknick M, Hielscher T, Liu XY, Fontebasso AM, Ryzhova M, Albrecht S, Jacob K, Wolter M, Ebinger M, Schuhmann MU, van Meter T, Fruhwald MC, Hauch H, Pekrun A, Radlwimmer B, Niehues T, von Komorowski G, Durken M, Kulozik AE, Madden J, Donson A, Foreman NK, Drissi R, Fouladi M, Scheurlen W, von Deimling A, Monoranu C, Roggendorf W, Herold-Mende C, Unterberg A, Kramm CM, Felsberg J, Hartmann C, Wiestler B, Wick W, Milde T, Witt O, Lindroth AM, Schwartzentruber J, Faury D, Fleming A, Zakrzewska M, Liberski PP, Zakrzewski K, Hauser P, Garami M, Klekner A, Bognar L, Morrissy S, Cavalli F, Taylor MD, van Sluis P, Koster J, Versteeg R, Volckmann R, Mikkelsen T, Aldape K, Reifenberger G, Collins VP, Majewski J, Korshunov A, Lichter P, Plass C, Jabado N, Pfister SM (2012) Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 22:425–437

    Article  PubMed  CAS  Google Scholar 

  22. Yan W, Zhang W, You G, Bao Z, Wang Y, Liu Y, Kang C, You Y, Wang L, Jiang T (2012) Correlation of IDH1 mutation with clinicopathologic factors and prognosis in primary glioblastoma: a report of 118 patients from China. PLoS ONE 7:e30339

    Article  PubMed  CAS  Google Scholar 

  23. SongTao Q, Lei Y, Si G, YanQing D, HuiXia H, XueLin Z, LanXiao W, Fei Y (2012) IDH mutations predict longer survival and response to temozolomide in secondary glioblastoma. Cancer Sci 103:269–273

    Article  PubMed  Google Scholar 

  24. Brandes AA, Franceschi E, Tosoni A, Benevento F, Scopece L, Mazzocchi V, Bacci A, Agati R, Calbucci F, Ermani M (2009) Temozolomide concomitant and adjuvant to radiotherapy in elderly patients with glioblastoma: correlation with MGMT promoter methylation status. Cancer 115:3512–3518

    Article  PubMed  CAS  Google Scholar 

  25. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003

    Article  PubMed  CAS  Google Scholar 

  26. Park SH, Min HS, Kim B, Myung J, Paek SH (2008) Galectin-3: a useful biomarker for differential diagnosis of brain tumors. Neuropathology 28:497–506

    Article  PubMed  Google Scholar 

  27. Bredel M, Bredel C, Juric D, Harsh GR, Vogel H, Recht LD, Sikic BI (2005) Functional network analysis reveals extended gliomagenesis pathway maps and three novel MYC-interacting genes in human gliomas. Cancer Res 65:8679–8689

    Article  PubMed  CAS  Google Scholar 

Download references

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Correspondence to Yeon-Lim Suh.

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Ha, S.Y., Kang, S.Y., Do, IG. et al. Glioblastoma with oligodendroglial component represents a subgroup of glioblastoma with high prevalence of IDH1 mutation and association with younger age. J Neurooncol 112, 439–448 (2013). https://doi.org/10.1007/s11060-013-1073-y

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