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.