Survival of patients with glioblastoma multiforme is not influenced by altered expression of p16, p53, EGFR, MDM2 or Bcl-2 genes

Deregulated expression of one or more growth control genes including p16, p53, EGF receptor (EGFR), MDM2 or Bcl-2 may contribute to the treatment resistance phenotype of GEM and generally poor patient survival, Clinically, GEM have been divided into two major groups defined by (1) histologic progression from a low grade tumor ("progressive" or "secondary" GEM) contrasted with (2) those which show initial clinical presentation without a prior history ("de novo" or "primary" GEM). Using molecular genetic analysis for p53 gene mutations together with immunophenotyping for overexpression of EGFR, up to four GEM variants can be distinguished, including the p53(+)/EGFR(+) progressive or the p53/EGFR(+) de novo variant. We examined the survival of 80 adult patients diagnosed with astrocytic GEM stratified by age category (>40, 41-60 or 61-80) to determine whether alterations in any one given growth control gene or whether different genetic variants of GEM (progressive verses de novo) were associated with different survival outcomes, Survival testing using Kaplan-Meier plots for GBM patients with or without altered expression of p16, p53, EGFR, MDM2 or Bcl-2 showed no significant differences by age group or by gene expression indicating a lack of prognostic value for GEM. Also the clinical outcome among patients with GEM showed no significant differences within each age category for any GEM variant including the progressive and de novo GEM variants indicating similar biologic behavior despite different genotypes, Using a pairwise comparison, one-third of the GEM with normal p16 expression showed accumulation of MDM2 protein and this association approached statistical significance (0.01 < P < 0.05) using the Bonferroni procedure. These GEM may represent a variant in which the p19(ARF)/MDM2/p53 pathway may be deregulated rather than the p16/cyclin D-CDK4/Rb pathway.