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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.

Authors :
Rosati A
Poliani PL
Todeschini A
Cominelli M
Medicina D
Cenzato M
Simoncini EL
Magrini SM
Buglione M
Grisanti S
Padovani A
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.

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