Department of Neurology, Daniel den Hoed Cancer Center, Erasmus University Hospital, Rotterdam, The Netherlands.
Neuro Oncol. 2009 Dec;11(6):737-46. doi: 10.1215/15228517-2009-011.
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 offers additional 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 on central pathology review, and on this latter group but after excluding anaplastic oligoastrocytoma (AOA) with necrosis. As a reference set for glioblastoma multiforme (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 oligodendroglial tumor. Tumors with combined 1p 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.
最近的研究表明，间变性少突胶质细胞瘤的临床结果是多变的，但组织学诊断也存在观察者间的差异。我们研究了 1p/19q 缺失、7 号染色体三体、表皮生长因子受体 (EGFR) 基因扩增 (EGFR(amp))、10 号染色体或 10q 缺失评估是否能提供组织学诊断以外的预后信息，并允许进行分子亚型分类。在这项研究中，我们使用了多中心前瞻性欧洲癌症研究与治疗组织 (EORTC) 第 26951 期临床试验中患者的临床数据和肿瘤样本，该试验研究了辅助使用丙卡巴肼、洛莫司汀 (CCNU) 和长春新碱化疗对间变性少突胶质细胞瘤的影响。荧光原位杂交用于评估染色体 1p、19q、7、10 和 10q 和 EGFR 的拷贝数异常。进行了三种不同的分析：基于局部病理诊断的所有纳入患者、基于中心病理复查确认存在间变性少突胶质细胞瘤的患者，以及对后者进行分析，但排除了伴有坏死的间变性少突星形细胞瘤 (AOA)。作为胶质母细胞瘤多形性 (GBM) 的参考组，使用前瞻性随机 III 期 GBM 研究 (EORTC 26981) 的患者作为基准。在 368 名患者中的 257 名患者中，中心病理复查证实存在间变性少突胶质细胞瘤。同时存在 1p 和 19q 缺失的肿瘤 (1p(loss)19q(loss)) 被组织病理学诊断为间变性少突胶质细胞瘤，更常位于额叶，并具有更好的预后。EGFR(amp) 阳性的间变性少突胶质细胞瘤更常为 AOA，更常位于额叶以外，生存情况与 GBM 相似。伴有坏死的 AOA 患者的存活率与 GBM 相似，而仅有内皮细胞增殖的 AOA 患者的总生存率更好。在单变量分析中，除了 10q 缺失外，所有分子因素均具有预后意义，但在多变量分析中，AOA、坏死和 1p(loss)19q(loss) 的组织病理学诊断仍然是独立的预后因素。伴有坏死的 AOA 肿瘤被认为是 WHO 分级 IV 肿瘤 (GBM)。在本研究分析的所有分子标志物中，特别是 1p/19q 的缺失具有预后意义，而其他标志物对经典组织学的预后价值贡献较小。
