Prognostic stratification of patients with anaplastic gliomas according to genetic profile

被引:54
作者
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
机构
[1] Grp Hosp Pitie Salpetriere, Assistance Publ Hop Paris, Serv Neurol Mazarin, F-75013 Paris, France
[2] Univ Paris 06, Fac Med, Paris, France
[3] INSERM, U711, Paris, France
[4] Grp Hosp Pitie Salpetriere, Assistance Publ Hop Paris, Lab Neuropathol R Escourolle, F-75013 Paris, France
[5] Hop Lariboisiere, Serv Anat Pathol, F-75475 Paris, France
关键词
anaplastic gliomas; EGFR; p53; 1p; 19q; recursive partitioning analysis;
D O I
10.1002/cncr.22211
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND. 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. METHODS. 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. RESULTS. The median survival was 33.5 months, and the median progress ion-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 I p 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. CONCLUSIONS. The search for 1p19q codeletion and EGFR receptor amplification provides a simple, clinically relevant prognostic subclassification of grade III gliomas. (c) 2006 American Cancer Society.
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页码:1891 / 1897
页数:7
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