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

Abstract

BackgroundIn 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 methodsLong-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 fluorescent in situ hybridization).ResultsMethylation 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.ConclusionsMolecular 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.

Impact of a novel biomarker, T‐LAK cell‐originating protein kinase (TOPK) expression on outcome in malignant glioma

“…Nowadays, standard treatment for high‐grade glioma is surgical resection followed by chemotherapy and irradiation, but clinical prognosis is still poor in patients with high‐grade glioma because of their aggressive capacity for proliferation and migration . Recent studies have provided us an increased knowledge on a number of molecular markers and/or gene mutations specific to human glioma, including the isocitrate dehydrogenase gene ( IDH1 ) mutation and methyl guanine methyl transferase promoter methylation, but have not yet led to the breakthrough of innovative therapeutic strategies for patients with gliomas …”

“…1,2 Recent studies have provided us an increased knowledge on a number of molecular markers and/or gene mutations specific to human glioma, including the isocitrate dehydrogenase gene (IDH1) mutation and methyl guanine methyl transferase promoter methylation, but have not yet led to the breakthrough of innovative therapeutic strategies for patients with gliomas. 3 On the other hand, recent studies strongly suggest that T-lymphokine-activated killer (T-LAK) cell-originating protein kinase (TOPK) may play master roles in tumorigenesis in various types of cancer, being a molecular target for malignant tumors. TOPK is a 322-amino acid serine-threonine kinase.…”

A Survival Score Based on Symptoms and Performance Status for Patients with High-grade Gliomas Receiving Radiochemotherapy

“…The survival outcomes of patients with a high-grade glioma are often poor and require significant improvement (1). A certain prolongation of the median survival time has already been achieved with the introduction of multi-modality treatment programs involving neurosurgery, radiation oncology and administration of systemic agents (1-3).…”

Sex-specific impact of patterns of imageable tumor growth on survival of primary glioblastoma patients

“…Previous studies have demonstrated that MGMT promoter methylation is a significant independent prognostic factor 37 and is more common among long-term survivors 30,38 . Despite having a relatively small sample of patients with known MGMT methylation status, our analysis was able to confirm that, for both males and females, MGMT methylation was more common among extreme survivors and was a significant independent prognostic factor.…”

“…Methylation of the MGMT promoter has been found to be more common in long-term survivors 30 , so we also assessed the impact of MGMT methylation on the survival of our population cohort. Ninety patients from the main cohort had available MGMT methylation status, which comprised of 32 females (12 methylated and 20 unmethylated) and 58 males (18 methylated and 40 unmethylated).…”