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首页> 外文期刊>Neuro-Oncology >Molecular analysis of anaplastic oligodendroglial tumors in a prospective randomized study: A report from EORTC study 26951
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Molecular analysis of anaplastic oligodendroglial tumors in a prospective randomized study: A report from EORTC study 26951

机译：一项前瞻性随机研究中的间变性少突胶质细胞瘤的分子分析：EORTC研究报告26951

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摘要

Recent studies have shown that the clinical outcome of anaplastic oligodendroglial tumors is variable, but also that the histological diagnosis is subject to interobserver variation. We investigated whether the assessment of 1p/19q codeletion, polysomy of chromosome 7, epidermal growth factor receptor (EGFR) gene amplification (EGFR~(amp)), and loss of chromosome 10 or 10q offersrnadditional prognostic information to the histological diagnosis and would allow molecular subtyping. For this study, we used the clinical data and tumor samples of the patients included in multicenter prospective phase III European Organisation for Research and Treatment of Cancer (EORTC) study 26951 on the effects of adjuvant procarbazine, chloroethyl cyclohexylnitrosourea (lomustine), and vincristine chemotherapy in anaplastic oligodendroglial tumors. Fluorescence in situ hybridization was used to assess copy number aberrations of chromosome 1p, 19q, 7, 10, and 10q and EGFR. Three different analyses were performed: on all included patients based on local pathology diagnosis, on the patients with confirmed anaplastic oligodendroglial tumors onrncentral pathology review, and on this latter group but after excluding anaplastic oligoastrocytoma (AOA) with necrosis. As a reference set for glioblastoma multi-forme (GBM), patients from the prospective randomized phase III study on GBM (EORTC 26981) were used as a benchmark. In 257 of 368 patients, central pathology review confirmed the presence of an anaplastic oligo-dendroglial tumor. Tumors with combined lp and 19q loss (1p~(loss)19q~(loss)) were histopathologically diagnosed as anaplastic oligodendroglioma, were more frequently located in the frontal lobe, and had a better outcome. Anaplastic oligodendroglial tumors with EGFR~(amp) were more frequently AOA, were more often localized outside the frontal lobe, and had a survival similar to that for GBM. Survival of patients with AOA harboring necrosis was in a similar range as for GBM, while patients with AOA with only endothelial proliferation had better overall survival. In univariate analyses, all molecular factors except loss of 10q were of prognostic significance, but on multivariate analysis a histopathological diagnosis of AOA, necrosis, and 1p~(loss)19q~(loss) remained independent prognostic factors. AOA tumors with necrosis are to be considered WHO grade IV tumors (GBM). Of all molecular markers analyzed in this study, especially loss of 1p/19q carried prognostic significance, while the others contributed little prognostic value to classical histology.
机译：最近的研究表明，间变性少突胶质细胞瘤的临床结果是可变的，而且组织学诊断也存在观察者间差异。我们调查了评估1p / 19q缺失，7号染色体的多体性，表皮生长因子受体（EGFR）基因扩增（EGFR〜（amp））以及10号或10q染色体丢失是否为组织学诊断提供了其他预后信息，并且是否允许分子亚型。在这项研究中，我们使用了多中心前瞻性III期欧洲癌症研究与治疗组织（EORTC）研究26951中所含患者的临床数据和肿瘤样品，以评估佐丙嗪，氯乙基环己基亚硝基脲（洛米汀）和长春新碱化疗的作用在间变性少突胶质细胞瘤中。荧光原位杂交用于评估1p，19q，7、10和10q染色体和EGFR的拷贝数畸变。进行了三种不同的分析：对所有包括基于局部病理诊断的患者，经中央病理检查证实为变性少突胶质神经胶质瘤的患者，以及对后者进行的分析，但排除了具有坏死的间变性少星形胶质细胞瘤（AOA）。作为多形性胶质母细胞瘤（GBM）的参考集，前瞻性GBM随机III期研究（EORTC 26981）的患者用作基准。在368例患者中的257例中，中心病理检查证实存在间变性少突胶质细胞瘤。经组织病理学诊断为合并lp和19q丢失（1p〜（损失）19q〜（损失））的肿瘤为间变性少突胶质神经胶质瘤，更常位于额叶，并具有更好的结局。伴有EGFR〜（amp）的间变性少突胶质细胞瘤的AOA频率更高，更常见于额叶外，并且存活率与GBM相似。具有坏死的AOA患者的生存率与GBM相似，而仅具有血管内皮增生的AOA患者的总生存率更高。在单变量分析中，除10q丢失外，所有分子因素均具有预后意义，但在多变量分析中，AOA的组织病理学诊断，坏死和1p〜（丢失）19q〜（丢失）仍是独立的预后因素。伴有坏死的AOA肿瘤被认为是WHO IV级肿瘤（GBM）。在这项研究中分析的所有分子标记中，尤其是丢失1p / 19q具有预后意义，而其他分子标记对经典组织学的预后价值很小。

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  • 来源
    《Neuro-Oncology》 |2009年第6期|737-746|共10页
  • 作者

    Mathilde C.M. Kouwenhoven; Thierry Gorlia; Johan M. Kros; Ahmed Ibdaih; Alba A. Brandes; Jacolien E.C. Bromberg; Karima Mokhtari; Sjoerd G. van Duinen; Johannes L. Teepen; Pieter Wesseling; Fanny Vandenbos; Wolfgang Grisold; Laszlo Sipos; Rene Mirimanoff; Charles J. Vecht; Anouk Allgeier; Denis Lacombe; Martin J. van den Bent;

  • 作者单位

    Departments of Neurology Daniel den Hoed Cancer Center, Erasmus University Hospital, Rotterdam, the Netherlands;

    European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium;

    Departments of Neurology Pathology Daniel den Hoed Cancer Center, Erasmus University Hospital, Rotterdam, the Netherlands;

    Department of Neurology-Mazarin University Pitie-Salpetriere Hospital, Assistance Publique-Hopitaux de Paris, Paris, France;

    Medical Oncology Department Unit, Bellaria-Maggiore Hospital, Bologna, Italy;

    Departments of Neurology Daniel den Hoed Cancer Center, Erasmus University Hospital, Rotterdam, the Netherlands;

    Department of Neuropathology, University Pitie-Salpetriere Hospital, Assistance Publique-Hopitaux de Paris, Paris, France;

    Department of Pathology and Neurology, Leiden University Medical Center, Leiden, the Netherlands;

    Department of Pathology, Elisabeth Casthuis, Til burg, the Netherlands;

    Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands;

    Department of Pathology, University Hospital Center, Nice, France;

    Ludwig Boltzmann Institute for Neurooncology and Kaiser Franz Josef Hospital, Vienna, Austria;

    National Institute of Neurosurgery, Budapest, Hungary;

    Department of Radiotherapy, University Central Hospital Vaudois, Lausanne, Switzerland;

    Department of Neurology, Medical Center Haaglanden, the Hague, the Netherlands;

    European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium;

    European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium;

    Departments of Neurology Daniel den Hoed Cancer Center, Erasmus University Hospital, Rotterdam, the Netherlands Department of Neuro-Oncology, Dr. Daniel den Hoed Cancer Center, P.O. Box 5201, AE Rotterdam, 3008 Netherlands;

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  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    1p; 19q; anaplastic oligoastrocytoma; anaplastic oligodendroglioma; EGFR; monosomy 10;

    机译：1p;19q;间变性少星形细胞瘤;间变性少突胶质细胞瘤表皮生长因子单体10;

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