Acta Neuropathologica

, Volume 128, Issue 4, pp 551–559 | Cite as

Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma

  • Felix Sahm
  • David Reuss
  • Christian Koelsche
  • David Capper
  • Jens Schittenhelm
  • Stephanie Heim
  • David T. W. Jones
  • Stefan M. Pfister
  • Christel Herold-Mende
  • Wolfgang Wick
  • Wolf Mueller
  • Christian Hartmann
  • Werner Paulus
  • Andreas von Deimling
Original Paper


Astrocytoma and oligodendroglioma are histologically and genetically well-defined entities. The majority of astrocytomas harbor concurrent TP53 and ATRX mutations, while most oligodendrogliomas carry the 1p/19q co-deletion. Both entities share high frequencies of IDH mutations. In contrast, oligoastrocytomas (OA) appear less clearly defined and, therefore, there is an ongoing debate whether these tumors indeed constitute an entity or whether they represent a mixed bag containing both astrocytomas and oligodendrogliomas. We investigated 43 OA diagnosed in different institutions employing histology, immunohistochemistry and in situ hybridization addressing surrogates for the molecular genetic markers IDH1R132H, TP53, ATRX and 1p/19q loss. In all but one OA the combination of nuclear p53 accumulation and ATRX loss was mutually exclusive with 1p/19q co-deletion. In 31/43 OA, only alterations typical for oligodendroglioma were observed, while in 11/43 OA, only indicators for mutations typical for astrocytomas were detected. A single case exhibited a distinct pattern, nuclear expression of p53, ATRX loss, IDH1 mutation and partial 1p/19q loss. However, this was the only patient undergoing radiotherapy prior to surgery, possibly contributing to the acquisition of this uncommon combination. In OA with oligodendroglioma typical alterations, the portions corresponding to astrocytic part were determined as reactive, while in OA with astrocytoma typical alterations the portions corresponding to oligodendroglial differentiation were neoplastic. These data provide strong evidence against the existence of an independent OA entity.


Mixed glioma Oligoastrocytoma 1p/19q ATRX TP53 IDH1 



The study was supported by the Medical Faculty Heidelberg PostDoc Fellowship and the DKFZ Intramural Funding Program, Priority Topic Intratumoral Heterogeneity, to FS. We wish to thank Tanja Goeck and Katrin Kalis for skillful technical assistance.

Supplementary material

401_2014_1326_MOESM1_ESM.pdf (4.7 mb)
Supplementary material 1 (PDF 4820 kb)
401_2014_1326_MOESM2_ESM.docx (37 kb)
Supplementary material 2 (DOCX 37 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Felix Sahm
    • 1
    • 2
  • David Reuss
    • 1
    • 2
  • Christian Koelsche
    • 1
    • 2
  • David Capper
    • 1
    • 2
  • Jens Schittenhelm
    • 3
  • Stephanie Heim
    • 4
  • David T. W. Jones
    • 5
  • Stefan M. Pfister
    • 5
    • 6
  • Christel Herold-Mende
    • 7
  • Wolfgang Wick
    • 8
    • 9
  • Wolf Mueller
    • 10
  • Christian Hartmann
    • 11
  • Werner Paulus
    • 4
  • Andreas von Deimling
    • 1
    • 2
  1. 1.Department of Neuropathology, Institute of PathologyRuprecht-Karls-University HeidelbergHeidelbergGermany
  2. 2.Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK)German Cancer Research Center (DKFZ)HeidelbergGermany
  3. 3.Department of Neuropathology, Institute of Pathology and NeuropathologyUniversity TübingenTübingenGermany
  4. 4.Institute of NeuropathologyUniversity Hospital MünsterMünsterGermany
  5. 5.Division of Pediatric NeurooncologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  6. 6.Department of Pediatric Oncology, Haematology and ImmunologyHeidelberg University HospitalHeidelbergGermany
  7. 7.Department of NeurosurgeryUniversity Hospital HeidelbergHeidelbergGermany
  8. 8.Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK)German Cancer Research Center (DKFZ)HeidelbergGermany
  9. 9.Department of Neurooncology at the National Center for Tumor DiseasesHeidelberg University HospitalHeidelbergGermany
  10. 10.Department of NeuropathologyUniversity Hospital LeipzigLeipzigGermany
  11. 11.Department for NeuropathologyInstitute of Pathology, Medizinische Hochschule HannoverHannoverGermany

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