The prognostic relevance of molecular alterations in glioblastomas for patients age < 50 years

Abstract

BACKGROUND. In patients with glioblastoma, age < 50 years was identified as a consistent prognostic variable. In addition, the prognosis for these patients may be determined by a complex interaction between age and genetic alterations. The objective of the current study was the molecular analysis of glioblastomas from adult patients age < 50 years ("young adults"). METHODS. The authors analyzed a set of 189 glioblastoma specimens. Fluorescence in situ hybridization was performed with a set of 10 chromosome probes (1p36, 1q25, centomere probe 7 [CEP7], 7p12/epidermal growth factor receptor gene (EGFR), CEP9, 9p21/p16, CEP10, 10q23/phosphatase and tesnin homolog gene (PTEN), 19p13, and 19q13). RESULTS. Patient age < 40 years was associated strongly with a favorable prognosis. Patients age a 40 years frequently showed EGFR amplification, loss of 9p, loss of 1Oq, and gain of chromosome 19. The patients with - 19q were age < 40 years. The survival was shorter for patients with EGFR amplification, gain of chromosome 7, loss of 9p, loss of 10q, and gain of chromosome 19. In contrast, the patients who had tumors with gain of chromosome 9 or loss of 19q had more favorable outcomes. In a multivariate analysis, gain of chromosome 9 (P = 0.026} and loss of 10q23 (P = 0.007} reached the level of independent prognostic value. In addition, the prognostic value of molecular alterations in patients age < 40 years and patients age > 40 years were examined separately. Consequently, EGFR amplification, - 9p, and + 9 were significant for both age groups, whereas gain of chromosome 7 and loss of 1Oq showed clinical importance only among patients age > 40 years. CONCLUSIONS. Adult patients age < 50 years with glioblastoma had molecularly distinct disease, and the age-dependent heterogeneity seen on the chromosomal level also applied at the clinical level. © 2005 American Cancer Society.