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. 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. 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. CONCLUSIONS: Absent/low-intensity GS expression pattern represents a valuable biomarker of both epilepsy and overall survival in GBM.
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. 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. 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. CONCLUSIONS: Absent/low-intensity GS expression pattern represents a valuable biomarker of both epilepsy and overall survival in GBM.
Authors: Michael Weller; Roger Stupp; Guido Reifenberger; Alba A Brandes; Martin J van den Bent; Wolfgang Wick; Monika E Hegi Journal: Nat Rev Neurol Date: 2009-12-08 Impact factor: 42.937
Authors: P J Miller; R S Hassanein; P G Giri; B F Kimler; P O'Boynick; R G Evans Journal: Int J Radiat Oncol Biol Phys Date: 1990-08 Impact factor: 7.038
Authors: W J Curran; C B Scott; J Horton; J S Nelson; A S Weinstein; A J Fischbach; C H Chang; M Rotman; S O Asbell; R E Krisch Journal: J Natl Cancer Inst Date: 1993-05-05 Impact factor: 13.506
Authors: Sharon Berendsen; Meri Varkila; Jérôme Kroonen; Tatjana Seute; Tom J Snijders; Frans Kauw; Wim G M Spliet; Marie Willems; Christophe Poulet; Marike L Broekman; Vincent Bours; Pierre A Robe Journal: Neuro Oncol Date: 2015-09-29 Impact factor: 12.300