Primary glioblastoma with oligodendroglial differentiation has better clinical outcome but no difference in common biological markers compared with other types of glioblastoma

Abstract

Background: Glioblastoma multiforme with an oligodendroglial component (GBMO) has been recognized in the World Health Organization classification-however, the diagnostic criteria, molecular biology, and clinical outcome of primary GBMO remain unclear. Our aim was to investigate whether primary GBMO is a distinct clinicopathological subgroup of GBM and to determine the relative frequency of prognostic markers such as loss of heterozygosity (LOH) on 1p and/or 19q, O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and isocitrate dehydrogenase 1 (IDH1) mutation.

Methods: We examined 288 cases of primary GBM and assessed the molecular markers in 57 GBMO and 50 cases of other primary GBM, correlating the data with clinical parameters and outcome.

Results: GBMO comprised 21.5% of our GBM specimens and showed significantly longer survival compared with our other GBM (12 mo vs 5.8 mo, P = .006); there was also a strong correlation with younger age at diagnosis (56.4 y vs 60.6 y, P = .005). Singular LOH of 19q (P = .04) conferred a 1.9-fold increased hazard of shorter survival. There was no difference in the frequencies of 1p or 19q deletion, MGMT promoter methylation, or IDH1 mutation (P = .8, P = 1.0, P = 1.0, respectively).

Conclusions: Primary GBMO is a subgroup of GBM associated with longer survival and a younger age group but shows no difference in the frequency of LOH of 1p/19q, MGMT, and IDH1 mutation compared with other primary GBM.

Keywords: 1p/19q; IDH1; MGMT; glioblastoma with an oligodendroglial component; histopathology.

Fig. 1.

A case of GBMO (ID 44) with 19q loss. There is (A) cellular and anaplastic predominant astrocytic differentiation with (B) prominent vascular hyperplasia and pseudopalisading necrosis. (C and D) A focal area of oligodendroglial differentiation with rounded anaplastic nuclei and perinuclear halo separated by hyperplastic blood vessels.

Fig. 2.

Kaplan–Meier plot of 264 GBM showing the association with overall survival of GBMO compared with other-GBM.

Fig. 3.

Kaplan–Meier plots of the association of the LOH status of 1p/19q with overall survival in (A) the molecular comparison subset, (B) the GBMO group only, (C) the other-GBM group only.

Fig. 4.

A forest plot representing Cox proportional multivariate analyses of overall survival, adjusted for age and gender.