Bcl-2 protein plays an important role in inhibiting apoptosis and protectin
g normal and neoplastic cells from toxicity. Bcl-2 overexpression in malign
ant tumors, on the other hand, may cause resistance against adjuvant treatm
ent. Since there are subpopulations of patients with glioma that differ con
siderably in their treatment benefit, it is important to identify prognosti
c factors for outcome and to tailor adjuvant protocols in accordance with s
pecific biological features of the respective tumor. The present study aime
d at investigating the role of bcl-2 expression in higher-grade glioma (WHO
grade III and IV). Bcl-2 expression was correlated with clinical and parac
linical parameters, and evaluated in univariate and multivariate statistica
l models. In addition, bcl-2-overexpressing human glioma cells in culture w
ere used for modeling the in vivo findings and for investigating the import
ance of bcl-2 for tumor resistance against cytotoxic treatment.
A group of 86 patients with higher-grade glioma were investigated. Anaplast
ic astrocytoma (AA; WHO G III, n = 29) showed bcl-2 expression in 48% of th
e cases, and immunohistochemical positivity was associated with a significa
ntly shorter survival time (p = 0.0068). In glioblastoma patients (GBM; WHO
G IV, n = 57), 51% of tumors were bcl-2 positive, but bcl-2 expression did
not correlate significantly with survival (p = 0.39). In a Cox proportiona
l hazards regression model, bcl-2 positivity was confirmed as a negative pr
ognostic parameter in AA, but not in GBM.
Bcl-2 overexpressing and control human glioma cell clones (T98MG line) were
treated in culture with the cytotoxic drugs carmustine (BCNU), paclitaxel,
vincristine, and doxorubicin. In addition, bcl-2-overexpressing and contro
l cells were infected with a retrovirus carrying the herpes-simplex-virus t
hymidine kinase gene (HSV-tk), and then treated with ganciclovir (GCV). Bcl
-2 overexpression significantly increased tumor cell resistance against all
of the above cytotoxic drugs, and also against HSV-TK/GCV mediated gene th
erapy.