Prognostic impact of molecular markers in a series of 220 primary glioblastomas

被引:104
作者
Houillier, C
Lejeune, J
Benouaich-Amiel, A
Laigle-Donadey, F
Criniere, E
Mokhtari, K
Thillet, J
Delaffre, JY
Hoang-Xuan, K
Sanson, M
机构
[1] Grp Hosp Pitie Salpetriere, Serv Neurol Mazarin, F-75013 Paris, France
[2] INSERM U711, Paris, France
[3] Mazarin Neurol Serv, Paris, France
[4] Univ Paris 06, Fac Med, Paris, France
[5] Grp Hosp Pitie Salpetriere, E Escourolle Lab Neuropathol, F-75013 Paris, France
关键词
glioblastoma; markers; prognosis; EGFR; MDM2;
D O I
10.1002/cncr.21819
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND. in contrast to oligodendrogliomas, molecular predictors of prognosis have not been consistently found in glioblastomas. However, genetic studies show that glioblastomas consist of several genetic subtypes and raise the possibility that molecular alterations could be predictive of survival. METHODS. A search for loss of heterozygosity (LOH) on chromosome 1p, 9p, 10q, 19q, EGFR (epidermal growth factor receptor), CDK4, and MDM2 (mouse double minute) amplifications, CDKN2A (INK4A/ARF) homozygous deletions, p53 expression, was performed in a series of 220 primary glioblastomas. The molecular alterations were then correlated with each other to identify distinct molecular pathways and with clinical parameters and the course of the disease to identify prognostic markers. RESULTS. Nonrandom associations were found between EGFR amplification and LOH10q, LOH9p, and INK4A/ARF deletion, LOH1p and LOH19q, and MDM2 and CDK4 amplification, whereas Mutual exclusions were found between p53 expression and EGFR amplification, LOH 9p/INK4A/ARF homozygous deletion, and MDM2 and CDK4 amplification. Age (P = 4.10(-5)) and performance status (P = .003) were the main predictors Of Outcome. In contrast, molecular markers were of limited impact: MDM2 amplification correlated with poor outcome on both univariate and multivariate analysis (P = .01) and EGFR amplification with good prognosis on multivariate analysis (P = .02). CONCLUSION. Despite their limited prognostic impact, the genetic markers investigated here outline distinct molecular pathways involved in glioblastoma tumorigenesis and warrant broader molecular screening.
引用
收藏
页码:2218 / 2223
页数:6
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