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Farewell to oligoastrocytoma: in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma
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  • 作者: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)
  • 关键词:Mixed glioma ; Oligoastrocytoma ; 1p/19q ; ATRX ; TP53 ; IDH1
  • 刊名:Acta Neuropathologica
  • 出版年:2014
  • 出版时间:October 2014
  • 年:2014
  • 卷:128
  • 期:4
  • 页码:551-559
  • 全文大小:1,740 KB
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  • 作者单位: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. Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, INF 224, 69120, Heidelberg, Germany
    2. Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 224, 69120, Heidelberg, Germany
    3. Department of Neuropathology, Institute of Pathology and Neuropathology, University T眉bingen, Calwerstra脽e 3, 72076, T眉bingen, Germany
    4. Institute of Neuropathology, University Hospital M眉nster, Pottkamp 2, 48149, M眉nster, Germany
    5. Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany
    6. Department of Pediatric Oncology, Haematology and Immunology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany
    7. Department of Neurosurgery, University Hospital Heidelberg, INF 400, 69120, Heidelberg, Germany
    8. Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
    9. Department of Neurooncology at the National Center for Tumor Diseases, Heidelberg University Hospital, INF 400, 69120, Heidelberg, Germany
    10. Department of Neuropathology, University Hospital Leipzig, Liebigstr. 24, 04103, Leipzig, Germany
    11. Department for Neuropathology, Institute of Pathology, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
  • ISSN:1432-0533
文摘
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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