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Age-related expression of p53, Mdm2, EGFR and Msh2 in glioblastoma multiforme
Objective:
Glioblastoma multiforme (GBM) is a major cause of morbidity and mortality in neurosurgical patients. Despite the overall poor prognosis a range in survival times exists. Many approaches have been undertaken to define patient subgroups based on molecular changes. The aim of this study was to assess a possible correlation between the immunohistochemical p53, Mdm2, EGFR and Msh2 expression and age.
Method:
143 patients (77 male, 66 female) were included in this retrospective study who underwent craniotomy for newly-diagnosed GBM between May 1994 and February 2000. For statistical analysis, patients were separated into three age groups: 1. < 40 years, 2. 40-60 years, 3. > 60 years. Immunohistochemical staining (IHC) was performed using anti-p53 (clone DO-1), anti-Mdm2 (clone IF-2), anti-EGFR (clone H11) and anti-Msh2 antibodies (clone AB-1). The results were compared with the Ki67/MIB-1 proliferation index (Ki67 PI) and patient survival.
Findings:
P53 protein expression was significantly decreasing with advanced age (p < 0.05) whereas EGFR and Mdm2 expression was increasing (p < 0.05; p=0.01). Msh2 expression was unrelated to age. Multivariate analysis revealed Msh2 protein expression as a significant predictor of prolonged survival (p=0.004) whereas p53, Mdm2 and EGFR were not associated with patient survival. P53, Mdm2, EGFR and Msh2 expression was not associated with the Ki67 PI.
Interpretation:
Our results support the hypothesis that in GBM patients a complex relationship exists between the p53, Mdm2 and EGFR expression and age. Msh2 expression is not related to age. Notably, nuclear Msh2 expression turned out to be an independent prognostic indicator.