PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme
PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme
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DOI：
10.1093/jnci/93.16.1246
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发表时间：
2001-08-15
影响因子：
10.3
通讯作者：
Jenkins, RB
中科院分区：
文献类型：
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作者：
Smith, JS;Tachibana, I;Jenkins, RB
背景。间变性星形细胞瘤患者的生存率变化很大。因此，预后标志物将有助于识别此类患者的临床亚群。由于特定的遗传改变与胶质母细胞瘤相关，我们研究了是否可以在间变性星形细胞瘤患者中检测到类似的遗传改变，并用于识别那些具有特别侵袭性疾病的患者。方法：收集梅奥诊所癌症中心和中北部癌症治疗组临床试验中新诊断的胶质瘤患者174例的组织标本，其中63例为间变性星形细胞瘤。多形性胶质母细胞瘤III期。通过荧光原位杂交、半定量聚合酶链反应和DNA测序检测7号和10号染色体上EGFR、PTEN和p53基因的变化。所有统计检验均为双侧检验。结果：间变性星形细胞瘤中PTEN突变、EGFR扩增、10号染色体q臂缺失的发生率明显低于多形性胶质母细胞瘤（P = 0.033, P = 0.001, P < 0.001）， p53突变发生率明显高于多形性胶质母细胞瘤（P < 0.001）。间变性星形细胞瘤患者的单因素生存分析发现，PTEN （P = 0.002）和p53 （P = 0.012）突变分别与生存期缩短和延长有统计学显著相关。间变性星形细胞瘤患者的多因素Cox分析显示，在调整患者年龄、研究中表现评分和肿瘤切除程度后，PTEN突变仍然是一个重要的预后因素（风险比= 4.34；95%可信区间= 1.82 ~ 10.34）。所有174例患者的多变量分类和回归树分析发现，EGFR扩增是60岁以上多形性胶质母细胞瘤患者延长生存期的独立预测因子。结论：PTEN突变和EGFR扩增分别是间变性星形细胞瘤患者和老年多形性胶质母细胞瘤患者预后的重要因素。
Background. Survival of patients with anaplastic astrocytoma is highly variable. Prognostic markers would thus be useful to identify clinical subsets of such patients. Because specific genetic alterations have been associated with glioblastoma, we investigated whether similar genetic alterations could be detected in patients with anaplastic astrocytoma and used to identify those with particularly aggressive disease. Methods: Tissue specimens were collected from 174 patients enrolled in Mayo Clinic Cancer Center and North Central Cancer Treatment Group clinical trials for newly diagnosed gliomas, including 63 with anaplastic astrocytoma. and III with glioblastoma multiforme. Alterations of the EGFR, PTEN, and p53 genes and of chromosomes 7 and 10 were examined by fluorescence in situ hybridization, semiquantitative polymerase chain reaction, and DNA sequencing. All statistical tests were two-sided. Results: Mutation of PTEN, amplification of EGFR, and loss of the q arm of chromosome 10 were statistically significantly less common in anaplastic astrocytoma than in glioblastoma multiforme (P =.033, P =.001, and P < .001, respectively), and mutation of p53 was statistically significantly more common (P < .001). Univariate survival analyses of patients with anaplastic astrocytoma identified PTEN (P =.002) and p53 (P =.012) mutations as statistically significantly associated with reduced and prolonged survival, respectively. Multivariate Cox analysis of patients with anaplastic astrocytoma showed that PTEN mutation remained a powerful prognostic factor after adjusting for patient age, on-study performance score, and extent of tumor resection (hazard ratio = 4.34; 95% confidence interval = 1.82 to 10.34). Multivariate classification and regression-tree analysis of all 174 patients identified EGFR amplification as an independent predictor of prolonged survival in patients with glioblastoma multiforme who were older than 60 years of age. Conclusion: PTEN mutation and EGFR amplification are important prognostic factors in patients with anaplastic astrocytoma and in older patients with glioblastoma multiforme, respectively.