title: Long-term survival in glioblastoma: methyl guanine methyl transferase (MGMT) promoter methylation as independent favourable prognostic factor.
abstract: BACKGROUND
  In spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and performance status) do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma.
  
  
  METHODS
  Long-term survivor group were 40 patients with glioblastoma with survival longer than 30 months. Control group were 40 patients with shorter survival and matched to the long-term survivor group according to the clinical prognostic factors. All patients underwent multimodality treatment with surgery, postoperative conformal radiotherapy and temozolomide during and after radiotherapy. Biopsy samples were tested for the methylation of MGMT promoter (with methylation specific polymerase chain reaction), IDH1 (with immunohistochemistry), IDH2, CDKN2A and CDKN2B (with multiplex ligation-dependent probe amplification), and 1p and 19q mutations (with fluorescentin situhybridization).
  
  
  RESULTS
  Methylation of MGMT promoter was found in 95% and in 36% in the long-term survivor and control groups, respectively (p < 0.001). IDH1 R132H mutated patients had a non-significant lower risk of dying from glioblastoma (p = 0.437), in comparison to patients without this mutation. Other mutations were rare, with no significant difference between the two groups.
  
  
  CONCLUSIONS
  Molecular and genetic testing offers additional prognostic and predictive information for patients with glioblastoma. The most important finding of our analysis is that in the absence of MGMT promoter methylation, longterm survival is very rare. For patients without this mutation, alternative treatments should be explored.
authors.affiliation: Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Uros
authors.initials: U
authors.lastname: Smrdel
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Ljubljana, Slovenia.
authors.forename: Mara
authors.initials: M
authors.lastname: Popovic
authors.affiliation: Faculty of Medicine, University of Maribor, Slovenia.
authors.forename: Matjaz
authors.initials: M
authors.lastname: Zwitter
authors.affiliation: Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Bostjancic
authors.affiliation: Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Andrej
authors.initials: A
authors.lastname: Zupan
authors.affiliation: Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Viljem
authors.initials: V
authors.lastname: Kovac
authors.affiliation: Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Damjan
authors.initials: D
authors.lastname: Glavac
authors.affiliation: Department of Mathematics and Computer Science, Faculty of Natural Sciences and Mathematics, University of Maribor, Slovenia.
authors.forename: Drago
authors.initials: D
authors.lastname: Bokal
authors.affiliation: Department of Mathematics and Computer Science, Faculty of Natural Sciences and Mathematics, University of Maribor, Slovenia.
authors.forename: Janja
authors.initials: J
authors.lastname: Jerebic
keywords: glioblastoma; long-term survival; methyl guanine methyl transferase; prognostic factor