Wang Xiang, Liu Yan-hui, Xie Fei, You Chao, Mao Qing
Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu 610041, China.
Zhonghua Wai Ke Za Zhi. 2013 Feb 1;51(2):166-70.
To analyze the long-term survivors of glioblastoma and to identify any prognostic factors that potentially contribute to survival.
Fifteen glioblastomas patients underwent surgery from June 2007 to April 2009 who survived longer than 3 years were enrolled in. Clinical characteristics such as age, location of tumor, extent of resection, and radiotherapy or chemotherapy were analyzed. The expressions of epidermal growth factor receptor (EGFR), tumor protein 53 (P53), phosphatase and tensin homolog (PTEN), O6-methylguanine-DNA methyltransferase (MGMT), isocitrate dehydrogenase 1 gene (IDH1), and neurofibromatosis type 1 (NF-1) in tumor samples were measured by immunohistochemical method, and the status of P53 and IDH1 were detected by direct DNA sequencing as well. And the patients who survived less than 1 year were set as control. Kaplan-Meier analysis was used to evaluate the prognostic factors.
The average age of patients at diagnosis was 45.6 years. And the overall survival time was 3-6 years (median survival time 3.5 years). Thirteen patients underwent a total resection, and 14 patients took orally temozolomide. The occurrence frequency of these molecular markers in long-term survivors was PTEN (13/15), IDH1 (13/15), IDH1 mutation (12/15), P53 (8/15), P53 mutation (7/15), EGFR (6/15), MGMT (4/15) and NF-1 (3/15). There was a good correlation between IDH1 protein expression and IDHI mutation, and between P53 protein expression and P53 mutation. And the survival analysis showed that age above 50 years at diagnosis (OR = 0.262, 95%CI: 0.102 - 0.672), total resection (OR = 0.372, 95%CI: 0.149 - 0.931) and combined oral temozolomide (OR = 0.131, 95%CI: 0.044 - 0.390) were favorable clinical prognostic factors. PTEN (OR = 0.201, 95%CI: 0.074 - 0.549) and IDH1 (OR = 0.151, 95%CI: 0.050 - 0.454) expression, IDH1 mutation (OR = 0.276, 95%CI: 0.108 - 0.709) in tumor cells contributed to a favorable prognosis.
There is probably no single molecular marker that is responsible for long-term survival of patients with glioblastoma, may be a balance between all these molecular events result in a favorable outcome.
分析胶质母细胞瘤的长期存活者，并确定任何可能有助于生存的预后因素。
纳入2007年6月至2009年4月接受手术且存活超过3年的15例胶质母细胞瘤患者。分析年龄、肿瘤位置、切除范围以及放疗或化疗等临床特征。采用免疫组化方法检测肿瘤样本中表皮生长因子受体（EGFR）、肿瘤蛋白53（P53）、磷酸酶和张力蛋白同源物（PTEN）、O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）、异柠檬酸脱氢酶1基因（IDH1）和1型神经纤维瘤病（NF-1）的表达，同时通过直接DNA测序检测P53和IDH1的状态。将存活时间少于1年的患者设为对照组。采用Kaplan-Meier分析评估预后因素。
患者诊断时的平均年龄为45.6岁。总生存时间为3至6年（中位生存时间3.5年）。13例患者接受了全切除，14例患者口服替莫唑胺。这些分子标志物在长期存活者中的出现频率分别为PTEN（13/15）、IDH1（13/15）、IDH1突变（12/15）、P53（8/15）、P53突变（7/15）、EGFR（6/15）、MGMT（4/15）和NF-1（3/15）。IDH1蛋白表达与IDHI突变之间以及P53蛋白表达与P53突变之间存在良好的相关性。生存分析表明，诊断时年龄大于50岁（OR = 0.262，95%CI：0.102 - 0.672）、全切除（OR = 0.372，95%CI：0.149 - 0.931）和联合口服替莫唑胺（OR = 0.131，95%CI：0.044 - 0.390）是有利的临床预后因素。肿瘤细胞中PTEN（OR = 0.201，95%CI：0.074 - 0.549）和IDH1（OR = 0.151，95%CI：0.050 - 0.454）的表达、IDH1突变（OR = 0.276，95%CI：0.108 - 0.709）有助于良好的预后。
可能没有单一的分子标志物可解释胶质母细胞瘤患者的长期存活，可能是所有这些分子事件之间的平衡导致了良好的结果。
