Prognosis of Glioblastoma With Oligodendroglioma Component is Associated With the IDH1 Mutation and MGMT Methylation Status

Abstract

Glioblastoma (GBM) with oligodendroglioma component (GBMO) is a newly described GBM subtype in the 2007 World Health Organization classification. However, its biological and genetic characteristics are largely unknown. We investigated the clinicopathological and molecular features of 34 GBMOs and compared the survival rate of these patients with those of patients with astrocytoma, oligodendroglioma, anaplastic oligoastrocytoma (AOA), and conventional GBMs in our hospital. GBMO could be divided into two groups based on the presence of an IDH1 mutation. The IDH1 mutation was more frequently found in secondary GBMO, which had lower frequencies of EGFR amplification but higher MGMT methylation than the wild type IDH1 group, and patients with mutant IDH1 GBMO were on average younger than those with wild-type IDH1. Therefore, GBMO is a clinically and molecularly heterogeneous subtype, largely belonging to a proneural and classical subtype of GBM. The survival rate of GBMO patients itself was worse than that of AOA patients but not significantly better than that of conventional GBM patients. GBMO survival was independent of the dominant histopathological subtype i.e., astrocyte-dominant or oligodendroglioma -dominant, but it was significantly associated with the IDH1 mutation and MGMT methylation status. Therefore, GBMO should be regarded as a separate entity from AOA and must be classified as a subtype of GBM. However, further study is needed to determine whether it is a pathologic variant or a pattern of GBM because GBMO has a similar prognosis to conventional GBMs.

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].…”

“…This genetic marker has been shown as an important predictor of prognostic and longer survival rate [3,4,5].…”

“…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].…”

“…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].…”

“…Before the introduction of combined radiochemotherapy with temozolomide, the use of chemotherapy in GBM was not universally recommended [17]. However, the presence of an oligodendroglial component has been regarded by some authors as an indicator of increased chemosensitivity, since GBMO tumors have been reported to frequently contain molecular genetic alterations, such as a loss of heterozygosity (LOH) [3,11,17].Temozolomide is an orally active alkylating agent that is used for patients newly diagnosed with glioblastoma multiform. The drug is well tolerated and provides a modest survival benefit [16].…”