p53 mutation and epidermal growth factor receptor overexpression in glioblastoma.

Recent molecular studies indicate two different genetic pathways leading to the development of glioblastoma; final progression of astrocytoma and de novo formation. To define the mutual relationships of cytogenetic changes in the pathogenesis of glioblastoma, molecular histopathologic alterations of p53 and epidermal growth factor receptor (EGFR) were evaluated by single stranded conformational polymorphion, reverse transcriptase-polymerase chain reaction and immunohistochemical stains in 15 primary and 21 secondary glioblastomas. Mutations in p53 gene and positive immunoreactivity to p53 protein (DO1) were more prevalent in secondary glioblastomas than in primary glioblastomas. A correlation between p53 mutations and p53 immunopositivities in glioblastomas was observed in 83.3% of the cases. All cases with positive p53 immunoreactivities showed p53 mutations; however, 13.9% of glioblastomas with p53 immuno-positivities lacked the relevant mutations. EGFR amplifications were detected in 73.3% of primary glioblastomas and 9.5% of secondary glioblastomas (p<0.001). The concurrence of p53 mutation and EGFR amplification was revealed in only 2 out of 15 primary glioblastomas and none among the secondary glioblastomas. Immunoreactivities for EGFR were noted in 66.7% of primary glioblastomas and in 9.5% of secondary glioblastomas (p<0.001). A correlation between EGFR amplification and EGFR immunopositivity in glioblastomas was observed in 91.7% of the cases. These data indicate that EGFR amplification and p53 mutations are two independent genetic events in the development of glioblastomas.