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

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Abstract

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, INF 224, 69120, Heidelberg, Germany

    Felix Sahm, David Reuss, Christian Koelsche, David Capper & Andreas von Deimling

  2. Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 224, 69120, Heidelberg, Germany

    Felix Sahm, David Reuss, Christian Koelsche, David Capper & Andreas von Deimling

  3. Department of Neuropathology, Institute of Pathology and Neuropathology, University Tübingen, Calwerstraße 3, 72076, Tübingen, Germany

    Jens Schittenhelm

  4. Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149, Münster, Germany

    Stephanie Heim & Werner Paulus

  5. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    David T. W. Jones & Stefan M. Pfister

  6. Department of Pediatric Oncology, Haematology and Immunology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany

    Stefan M. Pfister

  7. Department of Neurosurgery, University Hospital Heidelberg, INF 400, 69120, Heidelberg, Germany

    Christel Herold-Mende

  8. Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

    Wolfgang Wick

  9. Department of Neurooncology at the National Center for Tumor Diseases, Heidelberg University Hospital, INF 400, 69120, Heidelberg, Germany

    Wolfgang Wick

  10. Department of Neuropathology, University Hospital Leipzig, Liebigstr. 24, 04103, Leipzig, Germany

    Wolf Mueller

  11. Department for Neuropathology, Institute of Pathology, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Christian Hartmann

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  1. Felix Sahm
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Correspondence to Andreas von Deimling.

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Sahm, F., Reuss, D., Koelsche, C. et al. Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma. Acta Neuropathol 128, 551–559 (2014). https://doi.org/10.1007/s00401-014-1326-7

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  • DOI: https://doi.org/10.1007/s00401-014-1326-7

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