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.

Epidemiology and Outcome of Glioblastoma

“…Secondary GBM develops from lower grade astrocytoma or oligodendrogliomas, occurs in younger patients (mean age = 45 years), and often contains TP53 mutations as the earliest detectable alteration (5). Mutations in isocitrate dehydrogenase-1 (IDH1) and IDH2 are present in 70-80% of low-grade glioma and secondary GBM, and in only 5-10% of primary GBM (7)(8)(9). Strong link has been found between IDH mutations and genome-wide glioma cytosine-phosphate-guanine I and methylator phenotype (G-CIMP) across all subtypes of glioma (10).…”

“…Strong link has been found between IDH mutations and genome-wide glioma cytosine-phosphate-guanine I and methylator phenotype (G-CIMP) across all subtypes of glioma (10). The WHO recently added a rare subtype of GBM termed "GBM-0," with oligodendroglioma component, defined as GBM having areas resembling anaplastic oligodendroglioma, with features of GBM and necrosis without microvascular proliferation (7). According to the 2016 WHO classification of GBM multiforme, this tumor has been separated from the classical identity and is currently classified into three groups: GBM IDH-wild type (including giant cell GBM, gliosarcoma, and epithelioid GBM), GBM IDH-mutant, and GBM NOS (1).…”

Glioblastoma with Oligodendroglioma Component (GBMO) in an adolescent: a case report

“…Furthermore, according to the most recent WHO classification, in 2016, a new addition was made to this diagnosis: the evidence of isocitrate dehydrogenase (IDH) mutation, which is present on about 10% of gliobastomas [2]. This genetic marker has been shown as an important predictor of prognostic and longer survival rate [3,4,5].…”

“…Furthermore, according to the most recent WHO classification, in 2016, a new addition was made to this diagnosis: the evidence of isocitrate dehydrogenase (IDH) mutation, which is present on about 10% of gliobastomas [2]. This genetic marker has been shown as an important predictor of prognostic and longer survival rate [3,4,5].Moreover, the overall median survival of GBMO and GBM are still controversial, since it has shown a longer survival [4] in GBMO while others did not identify differences whatsoever [5].Regarding age, although GBMO has been said to have a younger onset than GBM, both are mainly seen on older ages, such as the 5th and 6th decades of life, being an extremely rare occurrence on children or adolescents [3,5,6].About gender, GBMO has been said as more prevalent in men at a 3,25:1 rate [3], but this prevalence is controversial, since many time GBMO is still misdiagnosed as a regular GBM or as anaplastic oligoastrocytoma (AOA). However, Karsy et al showed the rarity of this subtype of GBM and, moreover, how rare is its occurrence in children and adolescents [6].…”

How Our Practice of Histopathology, Especially Tumour Pathology has Changed in the Last Two Decades: Reflections from a Major Referral Center in Pakistan

“…Thus, GBM-O differ in clinical behavior and genetic alterations from conventional GBM. Appin et al, 2013) Since last year, we are performing the 1p/19q codeletion test for oligodendroglioma (and anaplastic oligodednroglioma) which provides important prognostic (associated with longer survival) and predictive (patient with codeletion of 1p/19q are very sensitive to procarbozine CCNU and vincristine (PCV) regimens with good response) information (Kros et al, 2007;Giannini et al, 2008) and even helps in diagnosis of difficult cases (astrocytomas and GBM do not show this codeletion). In 2014, we hope to start molecular tests for EGFR mutations (amplifications) which are common in high grade astrocytomas but mostly negative in anaplastic oligodendroglioma and mixed anaplastic oligoastrocytomas, thus helping in diagnosis in difficult cases (Schmitt et al, 2002); IDH1 and 2 mutations (which are seen in 50 to 80% of grade II and III astrocytomas and oligodendrogliomas, secondary GBM and GBM-O but seldom in primary GBM) and are associated with better prognosis (longer overall survival) (Yan et al, 2009;Gupta et al, 2011).…”