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

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. PATIENTS AND 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 fluorescent in situ hybridization). 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.

Evolutionarily distinctive species often capture more phylogenetic diversity than expected.

Evolutionary distinctiveness measures of how evolutionarily isolated a species is relative to other members of its clade. Recently, distinctiveness metrics that explicitly incorporate time have been proposed for conservation prioritization. However, we found that such measures differ qualitatively in how well they capture the total amount of evolution (termed phylogenetic diversity, or PD) represented by a set of species. We used simulation and simple graph theory to explore this relationship with reference to phylogenetic tree shape. Overall, the distinctiveness measures capture more PD on more unbalanced trees and on trees with many splits near the present. The rank order of performance was robust across tree shapes, with apportioning measures performing best and node-based measures performing worst. A sample of 50 ultrametric trees from the literature showed the same patterns. Taken together, this suggests that distinctiveness metrics may be a useful addition to other measures of value for conservation prioritization of species. The simplest measure, the age of a species, performed surprisingly well, suggesting that new measures that focus on tree shape near the tips may provide a transparent alternative to more complicated full-tree approaches.