Prognostic impact of molecular markers in a series of 220 primary glioblastomas
Article first published online: 27 MAR 2006
Copyright © 2006 American Cancer Society
Volume 106, Issue 10, pages 2218–2223, 15 May 2006
How to Cite
Houillier, C., Lejeune, J., Benouaich-Amiel, A., Laigle-Donadey, F., Criniere, E., Mokhtari, K., Thillet, J., Delattre, J.-Y., Hoang-Xuan, K. and Sanson, M. (2006), Prognostic impact of molecular markers in a series of 220 primary glioblastomas. Cancer, 106: 2218–2223. doi: 10.1002/cncr.21819
- Issue published online: 27 APR 2006
- Article first published online: 27 MAR 2006
- Manuscript Accepted: 17 NOV 2005
- Manuscript Revised: 31 OCT 2005
- Manuscript Received: 7 SEP 2005
- Delegation a la Recherche Clinique (AP-HP). Grant Number: MUL 03012
- Ligue Nationale contre le Cancer, comite d'Ile et Villaine
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.
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.
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).
Despite their limited prognostic impact, the genetic markers investigated here outline distinct molecular pathways involved in glioblastoma tumorigenesis and warrant broader molecular screening. Cancer 2006. © 2006 American Cancer Society.