Glioblastoma with oligodendroglioma component (GBM-O): molecular genetic and clinical characteristics

Abstract

Glioblastoma (GBM) is an aggressive primary brain tumor with an average survival of approximately 1 year. A recently recognized subtype, glioblastoma with oligodendroglioma component (GBM-O), was designated by the World Health Organization (WHO) in 2007. We investigated GBM-Os for their clinical and molecular characteristics as compared to other forms of GBM. Tissue samples were used to determine EGFR, PTEN, and 1p and 19q status by fluorescence in situ hybridization (FISH); p53 and mutant IDH1 protein expression by immunohistochemistry (IHC); and MGMT promoter status by methylation-specific polymerase chain reaction (PCR). GBM-Os accounted for 11.9% of all GBMs. GBM-Os arose in younger patients compared to other forms of GBMs (50.7 years vs. 58.7 years, respectively), were more frequently secondary neoplasms, had a higher frequency of IDH1 mutations and had a lower frequency of PTEN deletions. Survival was longer in patients with GBM-Os compared to those with other GBMs, with median survivals of 16.2 and 8.1 months, respectively. Most of the survival advantage for GBM-O appeared to be associated with a younger age at presentation. Among patients with GBM-O, younger age at presentation and 1p deletion were most significant in conferring prolonged survival. Thus, GBM-O represents a subset of GBMs with distinctive morphologic, clinical and molecular characteristics.

Figure 1

Glioblastoma with oligodendroglioma component. Typical features of oligodendroglial differentiation such as monotonous cells with round nuclei and perinuclear clearing or “halos” (A) are identified, along with “chicken wire” vasculature (B). In other areas of the tumor, elongated, hyperchromatic nuclei with irregular contours, indicative of astrocytic differentiation, are seen along with pseudopalisading necrosis (C) and microvascular proliferation (D), diagnostic features of glioblastoma.

Figure 2

Kaplan–Meier survival curves for all glioblastomas (GBMs) and glioblastomas with oligodendroglioma component (GBM‐Os) (A) and primary GBMs and GBM‐Os (B).

Figure 3

Kaplan–Meier survival curve of 1p deleted vs. 1p and 19q intact glioblastomas with oligodendroglioma component.