Department of Neurological Surgery, Wakayama Medical University School of Medicine, Kimiidera 811-1, Wakayama, 641-0012, Japan.
Kansai Molecular Diagnosis Network for CNS Tumors, Osaka, 540-0006, Japan.
Brain Tumor Pathol. 2020 Apr;37(2):50-59. doi: 10.1007/s10014-020-00363-1. Epub 2020 May 2.
Aging is a known negative prognostic factor in glioblastomas (GBM). Whether particular genetic backgrounds are a factor in poor outcomes of elderly patients with GBM warrants investigation. We aim to elucidate any differences between older and younger adult patients with IDH-wildtype GBM regarding both molecular characteristics and clinical outcomes. We collected adult cases diagnosed with IDH-wildtype GBM from the Kansai Network. Clinical and pathological characteristics were analyzed retrospectively and compared between older (≥ 70 years) and younger (≤ 50 years) cases. Included were 92 older vs. 33 younger cases. The older group included more patients with preoperative Karnofsky performance status score < 70 and had a shorter survival time than the younger group. MGMT promoter was methylated more frequently in the older group. TERT promoter mutation was more common in the older group. There were significant differences in DNA copy-number alteration profiles between age groups in PTEN deletion and CDK4 amplification/gain. In the older group, no molecular markers were identified, but surgical resection was an independent prognostic factor. Age-specific survival difference was significant in the MGMT methylated and TERT wildtype subgroup. Elderly patients have several potential factors in poor prognosis of glioblastomas. Varying molecular profiles may explain differing rates of survival between generations.
衰老在胶质母细胞瘤(GBM)中是一个已知的预后不良因素。特定的遗传背景是否是老年 GBM 患者预后不良的一个因素值得研究。我们旨在阐明 IDH 野生型 GBM 中年龄较大和年龄较小的成年患者之间在分子特征和临床结果方面的任何差异。我们从关西网络中收集了 IDH 野生型 GBM 的成年病例。回顾性分析了临床和病理特征,并比较了年龄较大(≥70 岁)和年龄较小(≤50 岁)患者之间的差异。包括 92 例年龄较大的患者和 33 例年龄较小的患者。年龄较大的组中术前 Karnofsky 表现状态评分<70 的患者更多,并且比年龄较小的组存活时间更短。MGMT 启动子在年龄较大的组中甲基化更为常见。TERT 启动子突变在年龄较大的组中更为常见。在 PTEN 缺失和 CDK4 扩增/增益方面,年龄组之间的 DNA 拷贝数改变谱存在显著差异。在年龄较大的组中,没有鉴定出分子标志物,但手术切除是独立的预后因素。在 MGMT 甲基化和 TERT 野生型亚组中,年龄特异性生存差异显著。老年患者在胶质母细胞瘤的预后不良方面有几个潜在的因素。不同的分子谱可能解释了不同代际之间的生存率差异。