Mixed Research Unit, UMR 975, INSERM, National Institute of Health and Medical Research-Pierre and Marie Curie University, Pitie-Salpetriere Group Hospital, Paris, France.
Cancer. 2011 Jul 1;117(13):3014-26. doi: 10.1002/cncr.25827. Epub 2011 Jan 18.
Although it has been demonstrated that the neuronal intermediate filament alpha-internexin (INA) is closely related to 1p19q codeletion in gliomas, its prognostic and predictive value has not yet been confirmed in a prospective trial. The authors of this report assessed the prognostic significance of INA expression and its correlation with relevant clinical and molecular characteristics in the prospective, randomized European Organization for Research and Treatment of Cancer (EORTC) 26951 trial of adjuvant procarbazine, lomustine, and vincristine (PCV) in patients with anaplastic oligodendroglial tumors (AOTs).
INA immunohistochemistry expression in tumors from 92 patients who were included in the EORTC 26951 trial was analyzed independently by 2 observers and was correlated with relevant clinical characteristics, including progression-free survival (PFS) and overall survival (OS), and with molecular features, including 1p/19q codeletion, isocitrate dehydrogenase 1 and 2 gene (IDH1/IDH2) mutation, and O-6 methylguanine-DNA methyltransferase (MGMT) promoter methylation status.
INA expression was observed in 33 tumors and was strongly correlated with 1p/19q codeletion, IDH1 mutations, and MGMT promoter methylation. It was associated with significantly better PFS and OS independent of the treatment received. By using Cox proportional hazard modeling for OS with stepwise selection, INA expression, patient age, and performance status were identified as independent prognostic factors. The results indicated that INA expression may have an impact on the efficacy of combined radiotherapy plus PCV.
In a homogeneously treated group of patients with grade III AOTs, INA expression had strong favorable prognostic significance for OS and may have predictive value for sensitivity to chemotherapy.
尽管已经证明神经元中间丝α-连接蛋白(INA)与胶质瘤 1p19q 缺失密切相关,但在前瞻性试验中尚未证实其预后和预测价值。本报告的作者评估了 INA 表达的预后意义及其与相关临床和分子特征的相关性,这些特征来自于前瞻性、随机的欧洲癌症研究与治疗组织(EORTC)26951 试验,该试验评估了替莫唑胺(PCV)辅助治疗间变性少突胶质细胞瘤(AOTs)患者的疗效。
通过 2 位观察者独立分析了纳入 EORTC 26951 试验的 92 例患者肿瘤中的 INA 免疫组化表达,并将其与相关临床特征(包括无进展生存期(PFS)和总生存期(OS))以及分子特征(包括 1p/19q 缺失、异柠檬酸脱氢酶 1 和 2 基因(IDH1/IDH2)突变和 O-6-甲基鸟嘌呤-DNA 甲基转移酶(MGMT)启动子甲基化状态)相关联。
在 33 个肿瘤中观察到 INA 表达,与 1p/19q 缺失、IDH1 突变和 MGMT 启动子甲基化强烈相关。独立于接受的治疗,INA 表达与显著更好的 PFS 和 OS 相关。通过使用 Cox 比例风险模型进行 OS 的逐步选择,INA 表达、患者年龄和表现状态被确定为独立的预后因素。结果表明,INA 表达可能对联合放化疗的疗效有影响。
在一组同质治疗的 III 级 AOTs 患者中,INA 表达对 OS 具有强烈的有利预后意义,并且可能对化疗敏感性具有预测价值。