IDH1 mutation is associated with lower expression of VEGF but not microvessel formation in glioblastoma multiforme
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Jiří Polívka Jr1,2,3, Martin Pešta2,4, Pavel Pitule1,2, Ondřej Hes5, Luboš Holubec2, Jiří Polívka3, Tereza Kubíková1,2 and Zbyněk Tonar1,2
1Department of Histology and Embryology, Charles University, Faculty of Medicine in Pilsen, 306 05 Pilsen, Czech Republic
2Biomedical Centre, Charles University, Faculty of Medicine in Pilsen, 306 05 Pilsen, Czech Republic
3Department of Neurology, Faculty Hospital Pilsen, 304 60 Pilsen, Czech Republic
4Department of Biology, Charles University, Faculty of Medicine in Pilsen, 306 05 Pilsen, Czech Republic
5Department of Pathology, Faculty Hospital Pilsen, 304 60 Pilsen, Czech Republic
Jiří Polívka Jr, email: [email protected]
Keywords: glioblastoma multiforme; isocitrate dehydrogenase; microvessel; biomarkers; microvascularity
Received: June 21, 2017 Accepted: February 10, 2018 Epub: February 20, 2018 Published: March 27, 2018
Introduction: Glioblastoma 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.
Methods: 52 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.
Results: 20 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).
Summary: No 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.
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