Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas

Abstract

We carried out a population-based study on low-grade diffuse gliomas in the Canton of Zurich, Switzerland (population 1.16 million). From 1980 to 1994, 987 astrocytic and oligodendroglial tumors were diagnosed, of which 122 (12.4%) were low-grade (WHO grade II). The incidence rates adjusted to the World Standard Population, per million population per year, were 2.28 for low-grade diffuse astrocytomas, 0.89 for oligoastrocytomas, and 2.45 for oligodendrogliomas. The survival rate (mean follow-up 7.5+/-4.8 years) was highest for patients with oligodendroglioma (78% at 5 years, 51% at 10 years), followed by those with oligoastrocytoma (70% at 5 years, 49% at 10 years) and fibrillary astrocytoma (65% at 5 years, 31% at 10 years). Survival of patients with gemistocytic astrocytoma was poor, with survival rates of 16% at 5 years and 0% at 10 years. Younger patients (<50 years) survived significantly longer than older patients (>50 years; P=0.013). DNA sequencing, performed in 84% of cases, revealed that TP53 mutations were most frequent in gemistocytic astrocytomas (88%), followed by fibrillary astrocytomas (53%) and oligoastrocytomas (44%), but were infrequent (13%) in oligodendrogliomas. The presence of TP53 mutations was associated with shorter survival of patients with low-grade diffuse gliomas (log-rank test; P=0.047), but when each histological type was analyzed separately, an association was observed only for oligoastrocytoma ( P=0.05). Loss on 1p and 19q were assessed by quantitative microsatellite analysis in 67% of cases. These alterations were frequent in oligodendrogliomas (1p, 57%; 19q, 69%), less common in oligoastrocytomas (1p, 27%; 19q, 45%), rare in fibrillary astrocytomas (1p, 7%; 19q, 7%), and absent in gemistocytic astrocytomas. None of these alterations were predictive of survival. These results establish the frequency of key genetic alterations in low-grade diffuse gliomas at a population-based level. Multivariate Cox's regression analysis indicates that only age and histological type, but not genetic alterations, are significant predictive factors.

The hypermethylation of the O6‐methylguanine‐DNA methyltransferase gene promoter in gliomas—correlation with array comparative genome hybridization results and IDH1 mutation

“…We detected a relatively high frequency of 1p/ 19q codeletion in oligodendrogliomas (93.3%) and in oligoastrocytomas (77.8%) compared with previous studies reporting the codeletion in 54-89% of oligodendrogliomas (Bigner et al, 1999;Okamoto et al, 2004;Miller et al, 2006;Jeuken et al, 2010). High frequency of 1p/19q deletions may reflect relatively strict histological criteria for oligodendroglioma in our laboratory.…”

Low-grade astrocytomas: the prognostic value of fibrillary, gemistocytic, and protoplasmic tumor histology

“…Patients present in the 4th decade of life, with males accounting for approximately 60% of cases. 21,33 In this study we report a median age of 36 years, with males constituting 59.2% of cases. Fibrillary astrocytomas are reported to have a 5 and 8year malignancyfree survival rate of 64% and 37%, respectively, and have a median survival ranging from 6 to 8 years.…”

Identification of genomic aberrations associated with shorter overall survival in patients with oligodendroglial tumors

“…This is of particular interest, as patients with oligodendrogliomas were traditionally thought to have a better outcome than patients with oligoastrocytomas or astrocytomas. [3][4][5]41 Considering that the histopathological distinction between ''pure'' oligodendrogliomas and mixed oligoastrocytomas is difficult and quite subjective, our data indicate that genetic analyses may be more important to stratify oligodendroglial tumors with respect to patient outcome.…”

“…1 In addition, patients with pure oligodendrogliomas are thought to have a better prognosis than patients with mixed gliomas. [3][4][5] The hallmark genetic aberration in oligodendrogliomas is the loss of genetic material from chromosome arms 1p and 19q, which is found in 60-80% of oligodendrogliomas and 50% of oligoastrocytomas. 6 Recently, it was described that the combined deletions of 1p and 19q in oligodendroglial tumors are mediated by an unbalanced translocation t(1;19) (q10;p10).…”