Long-term survival in glioblastoma: methyl guanine methyl transferase (MGMT) promoter methylation as independent favourable prognostic factor

Abstract

Objective

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.

Patients and Methods

Long-term survivor (LTS) group were 40 patients with glioblastoma with survival longer than 30 months. Control group were 40 patients with shorter survival and matched to the LTS 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 (methylation specific polymerase chain reaction), IDH1 (immunohistochemistry), IDH2, CDKN2A and CDKN2B (multiplex ligation-dependent probe amplification), and 1p and 19q mutations (fluorescent in situ hybridization).

Results

Methylation of MGMT promoter was found in 95% and in 36% in the LTS and control groups, respectively (p < 0.001). IDH1 R132H mutated patients had a non-significant lower risk of dying from glioblastoma (0.7), in comparison to patients without this mutation. Other mutations were rare, with no significant difference between the two groups.