title: Glutamine synthetase expression as a valuable marker of epilepsy and longer survival in newly diagnosed glioblastoma multiforme.
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.
  
  
  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: Neurology Clinic, Spedali Civili, Universityof Brescia, Brescia, Italy. a.rosati@meyer.it
authors: Anna
authors: A
authors: Rosati
authors: Pietro Luigi
authors: PL
authors: Poliani
authors: Alice
authors: A
authors: Todeschini
authors: Manuela
authors: M
authors: Cominelli
authors: Daniela
authors: D
authors: Medicina
authors: Marco
authors: M
authors: Cenzato
authors: Edda Lucia
authors: EL
authors: Simoncini
authors: Stefano Maria
authors: SM
authors: Magrini
authors: Michela
authors: M
authors: Buglione
authors: Salvatore
authors: S
authors: Grisanti
authors: Alessandro
authors: A
authors: Padovani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000150:complications / Q000175:diagnosis / Q000201:enzymology / Q000401:mortality*; D015331:Cohort Studies; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004827:Epilepsy / Q000209:etiology / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000150:complications / Q000175:diagnosis / Q000201:enzymology / Q000401:mortality*; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D005974:Glutamate-Ammonia Ligase; D045643:DNA Repair Enzymes