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. However, information about immunohistochemical expression in recurrent lesions is sparse.


OBJECTIVE
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 prognostic 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 expression of p53 (p < 0.0001) and msh2 (p = 0.0012), while the numbers of mdm2 (p = 0.02), EGFR (p < 0.0001), and msh2 positive specimens (p < 0.0001) were reduced. Chemotherapy was associated with reduced msh2 expression (p < 0.0001). Immunohistochemical variables were not associated with patient survival.


CONCLUSIONS
There are significant differences in the p53/mdm2/EGFR/msh2 expression patterns in initial v recurrent glioblastoma multiforme. There may be interactions between chemotherapy and changes in the msh2 expression.
Stark
A M
AM
Department of Neurosurgery, University of Kiel Medical Centre, Kiel, Germany. andstark@hotmail.com
Witzel
P
P
Strege
R J
RJ
Hugo
H-H
HH
Mehdorn
H M
HM
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology; D001932:Brain Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D004268:DNA-Binding Proteins; D005260:Female; D018773:Genes, erbB-1 / Q000235:genetics* / Q000276:immunology; D016158:Genes, p53 / Q000235:genetics* / Q000276:immunology; D005909:Glioblastoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D051718:MutS Homolog 2 Protein; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000276:immunology; D051736:Proto-Oncogene Proteins c-mdm2
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein