GENE AMPLIFICATION AS A PROGNOSTIC FACTOR IN PRIMARY BRAIN-TUMORS

The most reliable prognostic factors for patients with primary maligna nt brain tumors remain histology, age, and functional status, Manageme nt of these individuals might be improved by quantifying pertinent mol ecular markers. We have measured the gene dosage of the epidermal grow th factor receptor (EGFR), mouse double minute 2 (MDM2), and cyclin-de pendent kinase 4 (CDK4) genes in a series of brain tumor specimens and correlated their amplification status with standard prognostic factor s and survival. Individual tumor DNA was successively hybridized with probes for EGFR, MDM2, and CDK4. The signal was quantified by densitom etry, and amplification was defined as gene signal greater than or equ al to 2 times normal. Survival, age, Karnofsky performance status, and histology were correlated with gene amplification. Nineteen astrocyto mas, 20 anaplastic astrocytomas, and 70 glioblastomas had complete dat a available. Median survival with and without any form of gene amplifi cation was 70.7 and 88.6 weeks, respectively (P = 0.0369). For the EGF R gene alone, those with and without amplification had a median surviv al of 58.9 and 88.6 weeks, respectively (P 0.0104). By Cox analysis, o nly tumor histology (P = 0.04) and Karnofsky performance status (P = 0 .0157) were significant independent predictors of survival. Gene ampli fication by itself was not predictive of survival, even for glioblasto mas (P = 0.8249). The lack of correlation between gene amplification a nd survival for patients with primary malignant brain tumors may be be cause EGFR, MDM2, and CDK4 are only portions of larger signaling syste ms. Therefore, the lack of a direct correlation between a single gene and outcome is not entirely unexpected.