PAPER p53, mdm2, EGFR, and msh2 expression in paired initial and recurrent glioblastoma multiforme

Background: The clinical course of glioblastoma multiforme is characterised by invasive growth and regular recurrence. Many genetic alteration have been identified in the genesis of the disease. How-ever, information about immunohistochemical expression in recurrent lesions is sparse. Objectives: To determine (1) whether the p53/mdm2/EGFR/msh2 expression pattern differs in initial v recurrent glioblastoma multiforme; (2) whether a possible change in expression correlates with prog-nostic variables (progression-free survival time, total survival time); and (3) whether chemotherapy in addition to surgery and radiotherapy influences the p53/mdm2/EGFR/msh2 expression profile. Methods: 27 patients were studied. They met the following criteria: histologically confirmed diagnosis of glioblastoma multiforme (WHO IV); total tumour resection at initial craniotomy; at least one re-craniotomy for glioblastoma multiforme recurrence; age 21 years or older. All underwent radiotherapy of at least 54 Gy, and 17 received additional chemotherapy. Immunohistochemical staining of initial tumours and recurrences was done with the following monoclonal antibodies: anti-p53 (DO-1), anti-mdm2 (IF-2), anti-EGFR (H11), and anti-msh2 (AB-1). Results: In comparison with the initial tumour, recurrent lesions were characterised by reduced expres-sion of p53 (p < 0.0001) and msh2 (p = 0.0012), while the numbers of mdm2 (p = 0.02), EGF