The DSC-MRI procedure may provide insight into the IDH1/2 mutation and ATRX expression status and MGMT methylation profile of diffuse glioma; however, taking integrated oligodendroglioma into account limits the diagnostic performance of rCBV in non-invasively predicting the molecular subtype.
Univariate analyses showed that patient age, involvement of eloquent areas, involvement of the subventricular zone, presence of leptomeningeal seeding, Karnofsky Performance Status, extent of resection (EOR), MGMT promoter methylation, and presence of an oligodendroglioma component were prognostic of OS.
However, IDH mutation, MGMT methylation, and younger patient age (<55 years old) were significantly correlated with favorable OS (all P < 0.05) in our cohort of astrocytic and ODGs.
The most widely validated markers in neuro-oncology presently are: 1) <i>MGMT promoter methylation</i> as a prognostic and predictive marker in glioblastoma, 2) <i>co-deletion of 1p and 19q</i> differentiating oligodendrogliomas from astrocytomas, 3) <i>IDH1/2</i> mutations, and 4) select pathway-associated mutations.
A better prognosis was significantly associated with combined IDH1 mutation and MGMT methylation status (both positive vs both negative, HR 0.079 [95% CI 0.008-0.579], p=0.012), as well as histology (OG vs DA and OA, HR 0.158 [95% CI 0.022-0.674], p=0.011) and tumor size (<6 cm vs ≥6 cm, HR 0.120 [95% CI 0.017-0.595], p=0.008).
In oligodendroglioma (OG) and oligoastrocytoma (OA), presence of 1p/19q codeletions is highly predictive of response to treatment and is often associated with the methylated MGMT promoter; hence, this study queries whether the presence of 1p/19q codeletions in OG/OA correlates with a higher rate of PsP following therapy.
Significant correlation of MGMT hypermethylation with MGMT protein expression was identified by IHC in GBMs and oligodendrogliomas (P = 0.0001), but not by western blotting.
The relationship between chromosome 1p and 19q deletions and treatment responsive oligodendrogliomas is discussed, as are the newer advances relating to silencing of the MGMT gene in astrocytomas and mutations in the IDH-1 gene in both astrocytomas and oligodendrogliomas.
Our results indicate that oligodendrogliomas, empirically known to have a relatively favourable prognosis, are also the most homogeneous entities in terms of MGMT promoter methylation.
Other molecular alterations found in oligodendrogliomas include hypermethylation of the promoter for the MGMT gene, TP53 mutations, EGFR and platelet-derived growth factor/PDGFR alterations, and 9p and 10q loss.
Some of the most promising biomarkers to date include loss of chromosomes 1p/19q in oligodendrogliomas and expression of O-6-methylguanine-DNA methyltransferase (MGMT) or epidermal growth factor receptor (EGFR) status in glioblastomas.
1p36, 19q13, 10q22-26, and O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status were assessed in 46 paired early and progressive oligodendrogliomas from 23 patients.
Progressive low-grade oligodendrogliomas: response to temozolomide and correlation between genetic profile and O6-methylguanine DNA methyltransferase protein expression.
Twelve (92%) patients treated with CCNU had MGMT-negative lesions and their median survival was 73 months; 1 patient had an MGMT-positive oligodendroglioma and is alive at 28 months.