Dehais Caroline, Laigle-Donadey Florence, Marie Yannick, Kujas Michele, Lejeune Julie, Benouaich-Amiel Alexandra, Pedretti Marta, Polivka Marc, Xuan Khe-Hoang, Thillet Joelle, Delattre Jean-Yves, Sanson Marc
INSERM U711, Biologie des Interactions Neurones et Glie, Paris, France.
Cancer. 2006 Oct 15;107(8):1891-7. doi: 10.1002/cncr.22211.
There is a need to improve the current, controversial, and poorly reproducible classification of anaplastic gliomas, which represent a highly heterogeneous entity in terms of survival.
The impact of the most common genetic alterations on survival was investigated based on 156 anaplastic gliomas: Among the patients who were included, the gender ratio was 1.32, the median age was 45.5 years (range, 20-83 years), and the median Karnofsky performance status was 70 (range, 40-100). Genetic analysis included a search for loss of heterozygosity (LOH) on chromosomes 1p and 19q; amplification of chromosomes 9p and 10q and of the epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4) and mouse double-minute (MDM2) genes; and p53 expression.
The median survival was 33.5 months, and the median progression-free survival was 15.8 months. In a univariate analysis, LOH on 1p and 19q was correlated with longer survival, whereas p53 expression, LOH on 9p, LOH on 10q, amplified EGFR, and deleted CDKN2A were correlated with shorter survival. LOH on 1p and 19q were associated with oligodendrogliomas, LOH on 10q was related to EGFR amplification, and LOH on 1p and 19q was mutually exclusive with EGFR amplification and LOH on 10q. In a multivariate analysis, the significant prognostic factors were age, histology, LOH on 1p and 19q, and P16/CDKN2A deletion. Recursive partitioning analysis (RPA) divided the whole group hierarchically into 3 distinct prognostic subgroups: Group A with 1p19q codeletion (median survival, 98 months), Group B with EGFR amplification (median survival, 17 months), and Group CC (median survival, 31 months), providing a basis for a genetically based prognostic subclassification for patients with Grade III gliomas.
The search for 1p19q codeletion and EGFR receptor amplification provides a simple, clinically relevant prognostic subclassification of grade III gliomas.
间变性胶质瘤目前的分类存在争议且重复性差，需要加以改进，这类肿瘤在生存方面是高度异质性的实体。
基于156例间变性胶质瘤研究了最常见基因改变对生存的影响：纳入患者的性别比为1.32，中位年龄为45.5岁（范围20 - 83岁），中位卡氏功能状态评分为70（范围40 - 100）。基因分析包括检测1号染色体短臂（1p）和19号染色体长臂（19q）的杂合性缺失（LOH）；9号染色体短臂（9p）、10号染色体长臂（10q）以及表皮生长因子受体（EGFR）、细胞周期蛋白依赖性激酶4（CDK4）和双微体（MDM2）基因的扩增；以及p53表达情况。
中位生存期为33.5个月，中位无进展生存期为15.8个月。单因素分析中，1p和19q的LOH与较长生存期相关，而p53表达、9p的LOH、10q的LOH、EGFR扩增以及CDKN2A缺失与较短生存期相关。1p和19q的LOH与少突胶质细胞瘤相关，10q的LOH与EGFR扩增相关，且1p和19q的LOH与EGFR扩增及10q的LOH相互排斥。多因素分析中，显著的预后因素为年龄、组织学类型、1p和19q的LOH以及P16/CDKN2A缺失。递归分割分析（RPA）将整个队列分层划分为3个不同的预后亚组：A组为1p19q共缺失（中位生存期98个月），B组为EGFR扩增（中位生存期17个月），C组（中位生存期31个月），为基于基因的III级胶质瘤患者预后亚分类提供了依据。
检测1p19q共缺失和EGFR受体扩增可为III级胶质瘤提供简单且与临床相关的预后亚分类。
