GENE AMPLIFICATION AS A PROGNOSTIC FACTOR IN PRIMARY AND SECONDARY HIGH-GRADE MALIGNANT GLIOMAS

The purpose of this study was to examine the incidence of gene amplifi cation in patients with primary (de novo) and secondary high-grade gli omas (gliomas evolving from lower grade malignancies) and to assess it s prognostic significance. A total of 186 prospectively collected froz en surgical specimens were analyzed. Extracted DNA was examined by Sou thern blot using probes corresponding to the EGFR, CDK4, MDM2, N-MYC. CYCD1, PDGFR-alpha, MET, C-MYC oncogenes, Complete clinical data regar ding age, sex, tumor size, extent of surgical resection, postoperative therapy and patient survival were collected. We showed that EGFR foll owed by CDK4 were the most frequent oncogene amplifications. Oncogene amplification events were significantly more frequent in grade 4 than in grade 3 astrocytomas, mixed gliomas or oligodendrogliomas (P<0.001) . With respect to EGFR, there was a significant difference in the freq uency of amplification between primary and secondary gliomas (P=0.001) ; however, no difference in the amplification frequency of the other o ncogenes was observed. There was no apparent correlation between the o ccurrence cif gene amplification and patient survival, possibly becaus e the genes amplified in human gliomas are part of larger signaling pa thways.