Bcl-2 expression in higher-grade human glioma: A clinical and experimentalstudy

Citation
C. Fels et al., Bcl-2 expression in higher-grade human glioma: A clinical and experimentalstudy, J NEURO-ONC, 48(3), 2000, pp. 207-216
Citations number
57
Categorie Soggetti
Oncology
Journal title
JOURNAL OF NEURO-ONCOLOGY
ISSN journal
0167594X → ACNP
Volume
48
Issue
3
Year of publication
2000
Pages
207 - 216
Database
ISI
SICI code
0167-594X(200007)48:3<207:BEIHHG>2.0.ZU;2-K
Abstract
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.