MDM2 AND P53 EXPRESSION IN GLIOMAS - A MULTIVARIATE SURVIVAL ANALYSISINCLUDING PROLIFERATION MARKERS AND EPIDERMAL GROWTH-FACTOR RECEPTOR

p53 and the murine double minute 2 (MDM2) oncoprotein expression was e valuated in paraffin-embedded tissue from 61 patients with central ner vous system gliomas (53 astrocytomas and eight oligodendrogliomas) and related to proliferation-associated markers [i.e. proliferating cell nuclear antigen (PCNA), Ki-67 and nuclear organizer regions (NORs)] an d epidermal growth factor receptor (EGFR). We used the monoclonal anti bodies PC-10, MIB-1, DO-1, 1B10 and EGFR 113 and the colloid silver ni trate (AgNOR) technique. MDM2 and p53 were co-expressed in 28% of case s. A p53-positive/MDM2-negative phenotype was observed in 15% and a p5 3-negative/MDM2-positive phenotype in 20% of cases, There was a positi ve correlation of p53 and MDM2 expression with grade and proliferation indices, Univariate analysis in the group of diffuse astrocytomas sho wed that older age, high histological grade, high PCNA labelling index (LI) and high AgNOR score were associated with reduced overall surviv al (P<0.05). p53 L1, Ki-67 LI, AgNOR score, tumour location and grade influenced disease-free survival (P<0.05), whereas the only parameters affecting post-relapse survival were histological grade and Ki-67 LI (P<0.1). Multivariate analysis revealed that age, radiotherapy, PCNA L I and p53 LI were the independent predictors of overall survival. p53 LI, Ki-67 LI, MDM2 LI, EGFR LI, grade and type of therapy were indepen dent predictors of disease-free survival, and grade was the only indep endent predictor of post-relapse survival. Our results indicate that p 53 LI and MDM2 LI, EGFR expression as well as proliferation markers (P CNA and Ki-67) are useful indicators of overall and disease-free survi val in diffuse astrocytoma patients.