IDH1 mutation is associated with lower expression of VEGF but not microvessel formation in glioblastoma multiforme

Abstract

IntroductionGlioblastoma multiforme (GBM) represents the most malignant primary brain tumor characterized by pathological vascularization. Mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) were observed in GBM. We aimed to assess the intra-tumor hypoxia, angiogenesis and microvessel formation in GBM and to find their associations with IDH1 mutation status and patients prognosis.Methods52 patients with a diagnosis of GBM were included into the study. IDH1 R132H mutation was assessed by RT-PCR from FFPE tumor samples obtained during surgery. The expression of markers of hypoxia (HIF2α), angiogenesis (VEGF), tumor microvascularity (CD31, CD34, vWF, CD105), and proliferation (Ki-67) were assessed immunohistochemically (IHC). IDH1 mutation and IHC markers were correlated with the patient survival.Results20 from 52 GBM tumor samples comprised IDH1 R132H mutation (38.5%). The majority of mutated tumors were classified as secondary glioblastomas (89.9%). Patients with IDH1 mutated tumors experienced better progression-free survival (P = 0.037) as well as overall survival (P = 0.035) compared with wild type tumors. The significantly lower expression of VEGF was observed in GBM with IDH1 mutation than in wild type tumors (P = 0.01). No such association was found for microvascular markers. The increased expression of newly-formed microvessels (ratio CD105/CD31) in tumor samples was associated with worse patient’s progression-free survival (P = 0.026).SummaryNo increase in HIF/VEGF-mediated angiogenesis was observed in IDH1-mutated GBM compared with IDH1 wild type tumors. The histological assessment of the portion of newly-formed microvessels in tumor tissue can be used for the prediction of GBM patient’s prognosis.

Non-Invasive Estimation of Glioma IDH1 Mutation and VEGF Expression by Histogram Analysis of Dynamic Contrast-Enhanced MRI

“…Analysis of CGGA database and clinical practice in our hospital indicated that VEGF expression was significantly lower in IDH1 mut as compared to the wildtype counterpart. Some studies demonstrated that the expression of VEGF was inhibited in the IDH mut gliomas (15,16). These findings supported our results indirectly.…”

Association of Isocitrate Dehydrogenase (IDH) Status With Edema to Tumor Ratio and Its Correlation With Immune Infiltration in Glioblastoma

“…One of these consequences is the increased hypoxia-inducible factor 1-alpha (HIF-1α) that is frequently detected in patients with an IDH-1 mutation ( 19 , 20 ). On the contrary, the proliferation rate (Ki-67) and vascular endothelial growth factor (VEGF) levels are significantly lower in IDH-1 mutated tumors ( 21 , 22 ). However, little is known about the affinity for vasogenic edema in IDH-1 wildtype GBM ( 23 ).…”

Similarities Between Stem Cell Niches in Glioblastoma and Bone Marrow: Rays of Hope for Novel Treatment Strategies

“…According to the WHO 2016 classification of gliomas, 108 infiltrative gliomas of all histological grades can be divided into 3 subgroups: IDH1/2-mutant and 1p/19q-non-co-deleted glioblastoma, IDH1/2-mutant and 1p-19q-codeleted glioblastoma and IDH1/2 wildtype glioblastoma. 109,110 Polivka et al 111 describe that IDH1 -mutated glioblastoma is associated with lower levels of VEGF expression than IDH1 wild-type but not with angiogenesis. In our study, 1 glioblastoma sample was IDH1 mutated and we did not observe differences in VEGF levels in this tissue sample as compared with the 9 IDH1 wild-type glioblastoma samples.…”