Details

Autor(en) / Beteiligte

• Houillier, Caroline
• Lejeune, Julie
• Benouaich‐Amiel, Alexandra
• Laigle‐Donadey, Florence
• Criniere, Emmanuelle
• Mokhtari, Karima
• Thillet, Joelle
• Delattre, Jean‐Yves
• Hoang‐Xuan, Khe
• Sanson, Marc

Titel

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

Ist Teil von

• Cancer, 2006-05, Vol.106 (10), p.2218-2223

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2006

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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. Cancer 2006. © 2006 American Cancer Society. A molecular and clinical analysis of 220 primary glioblastoma found nonrandom associations and exclusions of molecular markers, suggesting the involvement of distinct pathways. Age and performance status were the main prognostic markers, whereas molecular markers such as EGFR (epidermal growth factor receptor) and MDM2 (mouse double minute) amplifications were of limited impact.