Zetterling Maria, Berhane Luwam, Alafuzoff Irina, Jakola Asgeir S, Smits Anja
Department of Neuroscience, Neurosurgery, Uppsala University, University Hospital, Uppsala, Sweden.
Department of Neuroscience, Neurology, Uppsala University, University Hospital, Uppsala, Sweden.
PLoS One. 2017 Nov 29;12(11):e0188419. doi: 10.1371/journal.pone.0188419. eCollection 2017.
In the 2016 WHO classification, the diagnosis of oligodendroglioma has been restricted to IDH mutated, 1p19q codeleted tumors (IDHmut-codel). IDHmut oligoastrocytoma is now classified either as oligodendroglioma or astrocytoma based on presence of 1p19q codeletion. There is growing evidence that this molecular classification more closely reflects patient outcome. Due to the strong association between IDHmut-codel with oligodendroglial morphology, the additional impact of these markers on prognostic accuracy is largely unknown. Our aim was to assess the prognostic impact of IDHmut-codel in an unselected cohort of morphologically classified oligodendroglial tumors.
We performed a retrospective chart review of oligodendroglial tumors (WHO grade II and III) operated since 1983. A total of 214 tumors were included, and molecular information was available for 96 tumors. The prognostic impact of IDHmut-codel together with clinical parameters was analyzed by multivariate Cox regression.
IDHmut-codel was registered in 64 tumors while for 150 tumors the molecular profile was negative for IDHmut-codel, unknown or incomplete. Comparison between the two groups showed that patients with IDHmut-codel tumors were younger (42 vs. 48 years), had more frequent frontal tumor location (48 vs. 33%) and presented more often with seizures (72 vs. 51%) and no signs of neurological impairment (14 vs. 30%) than patients harboring tumors with unknown or incomplete molecular profile. Multivariate survival analysis identified young age (HR 1.78 ≥ 40 years), the absence of neurological deficits or personality changes (HR 0.57), frontal tumor location (HR 0.64) and the presence of IDHmut-codel (HR 0.50) as independent predictors for longer survival, whereas tumor grade was not.
In this unselected single-institution cohort, the presence of IDHmut-codel was associated with more beneficial clinical parameters and was identified as an independent prognostic factor. We conclude that the classical oligodendroglioma genotype provides additional prognostic data beyond clinical characteristics, morphology and tumor grade.
在2016年世界卫生组织(WHO)分类中,少突胶质细胞瘤的诊断仅限于异柠檬酸脱氢酶(IDH)突变且1p19q共缺失的肿瘤(IDHmut-codel)。IDH突变型少突星形细胞瘤现在根据1p19q共缺失情况分类为少突胶质细胞瘤或星形细胞瘤。越来越多的证据表明,这种分子分类更能准确反映患者的预后。由于IDHmut-codel与少突胶质细胞形态之间存在密切关联,这些标志物对预后准确性的额外影响在很大程度上尚不清楚。我们的目的是评估IDHmut-codel在一组未经选择的形态学分类的少突胶质细胞瘤队列中的预后影响。
我们对自1983年以来接受手术的少突胶质细胞瘤(WHO二级和三级)进行了回顾性病历审查。共纳入214例肿瘤,其中96例肿瘤有分子信息。通过多变量Cox回归分析IDHmut-codel与临床参数的预后影响。
64例肿瘤检测到IDHmut-codel,150例肿瘤的分子特征为IDHmut-codel阴性、未知或不完整。两组比较显示,与分子特征未知或不完整的肿瘤患者相比,IDHmut-codel肿瘤患者更年轻(42岁对48岁),肿瘤位于额叶的频率更高(48%对33%),癫痫发作更频繁(72%对51%),且无神经功能缺损体征(14%对30%)。多变量生存分析确定年轻(年龄≥40岁,风险比[HR]1.78)、无神经功能缺损或人格改变(HR 0.57)、肿瘤位于额叶(HR 0.64)和存在IDHmut-codel(HR 0.50)是生存时间更长的独立预测因素,而肿瘤分级不是。
在这个未经选择的单机构队列中,IDHmut-codel的存在与更有利的临床参数相关,并被确定为独立的预后因素。我们得出结论,经典的少突胶质细胞瘤基因型除了临床特征、形态学和肿瘤分级外,还能提供额外的预后数据。