Back to Search
Start Over
Glutamine synthetase expression as a valuable marker of epilepsy and longer survival in newly diagnosed glioblastoma multiforme.
Glutamine synthetase expression as a valuable marker of epilepsy and longer survival in newly diagnosed glioblastoma multiforme.
- Source :
-
Neuro-oncology [Neuro Oncol] 2013 May; Vol. 15 (5), pp. 618-25. Date of Electronic Publication: 2013 Feb 14. - Publication Year :
- 2013
-
Abstract
- Background: Glutamine synthetase (GS) is an astrocytic enzyme catalyzing the conversion of glutamate and ammonia to glutamine. Its up-regulation has been related to higher tumor proliferation and poor prognosis in extra-cerebral tumors. We have previously reported a GS deficiency in patients with glioblastoma multiforme (GBM) who also developed epilepsy, which is a favorable prognostic factor in glioma. Here, we investigated the prognostic value of GS expression in patients with GBM with or without epilepsy and its correlation with survival.<br />Methods: We conducted a clinical and histopathological study on 83 (52 males) consecutive patients with newly diagnosed GBM. Immunohistochemical expression of GS was scored semi-quantitatively on the basis of cell number, staining intensity, and distribution of immunoreactive cells. Several clinical and neuropathological variables were analyzed in relation to survival and GS expression.<br />Results: Median age at diagnosis was 62 years. At the last evaluation, with a median follow-up of 11.5 months (range, 1.5-58 months), 5 patients (6%) were still alive and 78 (94%) were dead. GS expression patterns in neoplastic cells were inversely correlated to the presence of epilepsy (P < .0001 for intensity and P < .009 for homogeneity of GS distribution, respectively). Univariate analysis showed that RPA score, epilepsy, O6-methylguanine-DNA methyltransferase (MGM)T status, application of Stupp protocol, and GS intensity pattern had a significant impact on survival. Absent/low intensity of GS expression was significantly associated with a longer survival in both uni- (19 vs 8 months; P < .0005) and multivariate (P = .003) analyses.<br />Conclusions: Absent/low-intensity GS expression pattern represents a valuable biomarker of both epilepsy and overall survival in GBM.
- Subjects :
- Adult
Aged
Aged, 80 and over
Brain Neoplasms complications
Brain Neoplasms diagnosis
Brain Neoplasms enzymology
Cohort Studies
DNA Methylation
DNA Modification Methylases genetics
DNA Repair Enzymes genetics
DNA, Neoplasm genetics
Epilepsy etiology
Female
Follow-Up Studies
Glioblastoma complications
Glioblastoma diagnosis
Glioblastoma enzymology
Glutamate-Ammonia Ligase genetics
Humans
Immunoenzyme Techniques
Male
Middle Aged
Neoplasm Staging
Prognosis
Survival Rate
Tumor Suppressor Proteins genetics
Brain Neoplasms mortality
Epilepsy mortality
Glioblastoma mortality
Glutamate-Ammonia Ligase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1523-5866
- Volume :
- 15
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Neuro-oncology
- Publication Type :
- Academic Journal
- Accession number :
- 23410662
- Full Text :
- https://doi.org/10.1093/neuonc/nos338