title: Multicentric Glioma Develops via a Mutant IDH1-Independent Pathway: Immunohistochemical Study of Multicentric Glioma.
abstract: Multicentric gliomas are very rare. Due to differences in their tumor types they remain enigmatic. We focused on the pathogenesis of multicentric gliomas and compared their immunoprofile with that of solitary gliomas. This retrospective study included 6 males and 8 females with multicentric glioma (8 glioblastomas, 2 anaplastic astrocytomas, 4 diffuse astrocytomas). Their age ranged from 27 to 75 years and all were treated between 2004 and June 2015. The expression of mutant isocitrate dehydrogenase 1 (IDH1), α-thalassemia X-linked intellectual disability (ATRX), p53, phosphatase and tensin homolog (PTEN), and epidermal growth factor receptor (EGFR) was examined immunohistochemically; for 1p19q analysis we used fluorescence in situ hybridization (FISH). In all patients, immunohistochemical staining was negative for mutant IDH1 and cytoplasmic PTEN; only 1 patient (7.1%) manifested nuclear PTEN positivity. FISH for 1p19q codeletion was negative in all 9 examined samples; 5 of 14 specimens (35.7%) were p53-positive, 9 (64.3%) were EGFR-positive, and 4 (28.6%) were ATRX-negative. The MIB-1 labeling index was 0.9-15.6% for grades II and III, and ranged between 17.3 and 52.4% for glioblastoma. Our results suggest that the pathogenesis of multicentric gliomas is different from the mutant IDH1-R132H pathogenesis of lower-grade glioma and secondary glioblastomas. More studies are needed to confirm the molecular mechanisms underlying the pathogenesis of multicentric glioma.
authors.affiliation: Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Vega
authors.initials: V
authors.lastname: Karlowee
authors.forename: Vishwa Jeet
authors.initials: VJ
authors.lastname: Amatya
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hirano
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takayasu
authors.forename: Ryo
authors.initials: R
authors.lastname: Nosaka
authors.forename: Manish
authors.initials: M
authors.lastname: Kolakshyapati
authors.forename: Masako
authors.initials: M
authors.lastname: Yoshihiro
authors.forename: Yukio
authors.initials: Y
authors.lastname: Takeshima
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Arita
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kurisu
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Yamasaki
mesh_terms: D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D004265:DNA Helicases / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000075924:X-linked Nuclear Protein
chemical_list: D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein