Epidemiological Study of Molecular and Genetic Classification in Adult Diffuse Glioma

Introduction

Based on the 2007 World Health Organization (WHO) categorization, glioma as the most common primary brain tumor, is classified as grade I to IV based on histopathological and clinical criteria WHO grade I gliomas are often treated by surgical evacuation, whereas WHO grade II or III gliomas are wildly invaded on brain and have a catastrophic prognosis [1, 2]. WHO grade IV tumors (glioblastomas), demonstrated a mean survival rate of only 15-18 months, even after total resection considering of surgery and adjuvant therapy [3]. In past decade, the genes encoding IDH1 were depicted to be highly mutated in low-grade gliomas and a subgroup of GBM [4]. In further, IDH1 mutations were reported to find in 70–80 % of WHO grade II or III astrocytoma, oligodendrogliomas, and oligoastrocytomas, whereas a small group (3–5%) were found to harbor IDH2 mutations [5]. Moreover, mutations of IDH1,2 are mutually specific in gliomas, containing IDH1 mutations in 70–80% of cases [6, 7]. In other type of brain tumors, diffuse astrocytoma frequently carry TP53 mutations [8]. Oligoastrocytomas demonstrate either TP53 mutations or loss of 1p/19q [9]. Although the mutation that leads to 1p/19q codeletion is distinctive of oligodendroglioma, positive 1p/19q codeletion have been evaluated in cases with glioblastoma histopathology [10]. By itself, the 1p/19q codeletion, is inadequate for a diagnosis of gliomas and IDH-mutant or 1p/19q codeleted [11, 12]. Due to lack of characterizing, a positive 1p/19q codeletion outcomes can be bewilder, especially in tumors without classic oligodendroglioma morphology [13, 14]. The present research evaluates a quantitative basis for the genetical classification of gliomas by combining a number of patients from central institution. The specific purposes will determine the various combinations of genetic mutation and to assess whether molecular classification using IDH1 mutations, TP53 mutations, ATRX and 1p19qloss assess reliable outcome data.

Results

In this study, the patients included in this study consist of 53 patients, 34 men (64.1%) and 19 women (3.9%) and mean age: 43.2 ± 10.08 years. T-test was done and there was no significant relation between age and sex.

Discussion

Malignant diffuse glioma remains an outstanding threat to human health worldwide and impact a huge burden of diseases for health care systems. It is well established that the prognosis of patients with high-grade malignant glioma is considerably poor and IDH1/2 mutations have been detected in numerous of GBM patients [9]. We demonstrated the majority of low-grade diffuse gliomas carry at least one of the subheading genetic alterations: IDH1 mutation, IDH2 mutation, TP53 mutation, and 1p/19q loss. Most common histopathology was astrocytoma and grade 2 WHO.

These findings confirm previous data depicted that IDH1 mutations occur at a very early stage and are the most common genetic changes in astrocytic and oligodendroglia low-grade diffuse gliomas. Negative results in four genetical descriptive, suggests the alternative genetic roots involving as yet not identified genomes that lead pathogenesis of a small group of low-grade diffuse gliomas. The superiority of tumors with TP53 mutation and IDH1/2 mutation were histopathological diagnosed as diffuse astrocytoma, whereby only one-third of tumors with 1p/19q loss ± IDH1/2 mutation were oligodendroglioma. This demonstrate that tumor cells with IDH1/2 mutations disposed to have an astrocytic type. In oligodendroglioma, 1p19q co-deletion significantly showed higher among other tumors.

It is known that IDH1 mutations are a significant factor of approving outcome in patients with glioblastoma. Ramin et al, IDH mutation in more than 60 years old patients found that in 19.2% of astrocytoma and 50% of oligodendroglioma tumors [15]. Related tumors to IDH1/2-mutant are found to basically demonstrate in adolescents rather than younger children or adult [10, 12]. We found that more than half of patients had IDH1, 2 mutation. There is growing engrosment in the prevalence of IDH1/2 mutations in various types of glioma. Whereas, Wang et al, demonstrated that IDH1,2 in 55.2% of patients with diffuse gliomas [1]. Kim et al showed 37% of patients with diffuse glioma had correlated IDH1,2 and 1p19q co-deletion mutations [16]. As we depicted, P53 mutation was found in 40% of diffuse glioma. So far, Jin et el. in meta-analysis study showed p53 in 41% of patient in low grade glioma and 63% in high grade one [17]. TP53 mutations and loss of 1p/19q is considerably important, since these changes are markers of poor and more approving outcomes, respectively.

Cancer Genome Atlas described 93% altered p53 mutation in patients with positive IDH mutation in diffuse glioma [18]. The prognostic role of IDH1 mutation in WHO grade II glioma remains unclear. One study in 49 patients with diffuse astrocytoma showed a significant relation between the presence of IDH1 mutations and longer survival [19]. Despite IDH1/2 mutations are not prognostic, we proposed that IDH1/2 mutation be assessed, cause this is the most reliable factors for a diffuse WHO grade II glioma and excludes other gliomas, including pilocytic astrocytomas, ependymomas, and non-neoplastic [20, 21]. As we showed, 35% of patients had ATRX mutations. Johnson et al. found that p53 mutation in 5.3% and ATRX in 24.2% of children in low grade glioma [22]. In addition, Brat et al. evaluated that BRAF, SMARCA4, ATRX and TP53 related to recurrency of diffuse gliomas [18].

Conclusion

In conclusion, our study discloses relation between IDH1, 2 mutant gliomas nearly in half of patients, following by p53. We provide further information that there were no association between histopathology, tumor location, clinical outcomes and IDH1, 2, ATRX, TP53 and 1p/19q codeletion. Further studies on the genetically results IDH mutation should lead to more comprehensive understanding of the underlying association between IDH mutations and their impacts on the outcome of diffuse gliomas.