Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
PLoS One. 2013 Jun 28;8(6):e67421. doi: 10.1371/journal.pone.0067421. Print 2013.
Recurrence and progression to higher grade lesions are characteristic behaviors of gliomas. Though IDH1 mutation frequently occurs and is considered as an early event in gliomagenesis, little is known about its role in the recurrence and progression of gliomas. We therefore analysed IDH1 and IDH2 status at codon 132 of IDH1 and codon 172 of IDH2 by direct sequencing and anti-IDH1-R132H immunohistochemistry in 53 paired samples and their recurrences, including 29 low-grade gliomas, 16 anaplastic gliomas and 8 Glioblastomas. IDH1/IDH2 mutation was detected in 32 primary tumors, with 25 low-grade gliomas and 6 anaplastic gliomas harboring IDH1 mutation and 1 low-grade glioma harboring IDH2 mutation. All of the paired tumors showed consistent IDH1 and IDH2 status. Patients were analyzed according to IDH1 status and tumor-related factors. Malignant progression at recurrence was noted in 22 gliomas and was not associated with IDH1 mutation. Survival analysis revealed patients with IDH1 mutated gliomas had a significantly longer progression-free survival (PFS) and overall survival (OS). In conclusion, this study demonstrated a strong tendency of IDH1/IDH2 status being consistent during progression of glioma. IDH1 mutation was not a predictive marker for malignant progression and it was a potential prognostic marker for gliomas of Chinese patients.
复发性和向高级别病变的进展是神经胶质瘤的特征性行为。尽管 IDH1 突变经常发生并且被认为是神经胶质瘤发生的早期事件,但对其在神经胶质瘤复发和进展中的作用知之甚少。因此,我们通过直接测序和抗 IDH1-R132H 免疫组织化学分析了 53 对样本及其复发性肿瘤中 IDH1 第 132 位密码子和 IDH2 第 172 位密码子的 IDH1 和 IDH2 状态,包括 29 例低级别神经胶质瘤、16 例间变性神经胶质瘤和 8 例胶质母细胞瘤。在 32 例原发性肿瘤中检测到 IDH1/IDH2 突变,其中 25 例低级别神经胶质瘤和 6 例间变性神经胶质瘤携带 IDH1 突变,1 例低级别神经胶质瘤携带 IDH2 突变。所有配对肿瘤均显示出一致的 IDH1 和 IDH2 状态。根据 IDH1 状态和肿瘤相关因素对患者进行分析。在 22 例神经胶质瘤中观察到恶性进展,但与 IDH1 突变无关。生存分析显示 IDH1 突变型神经胶质瘤患者的无进展生存期(PFS)和总生存期(OS)显著延长。总之,本研究表明 IDH1/IDH2 状态在神经胶质瘤进展过程中具有很强的一致性趋势。IDH1 突变不是恶性进展的预测标志物,而是中国患者神经胶质瘤的潜在预后标志物。