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The Correlation of Fluorescence of Protoporphyrinogen IX and Status of Isocitrate Dehydrogenase in Gliomas.

Authors
  • Ohba, Shigeo1
  • Murayama, Kazuhiro2
  • Kuwahara, Kiyonori1
  • Pareira, Eriel Sandika3
  • Nakae, Shunsuke1
  • Nishiyama, Yuya1
  • Adachi, Kazuhide1
  • Yamada, Seiji4
  • Sasaki, Hikaru3
  • Yamamoto, Naoki5
  • Abe, Masato6
  • Mukherjee, Joydeep7
  • Hasegawa, Mitsuhiro1
  • Pieper, Russell O7
  • Hirose, Yuichi1
  • 1 Department of Neurosurgery, Fujita Health University, Toyoake, Japan. , (Japan)
  • 2 Department of Radiology, Fujita Health University, Toyoake, Japan. , (Japan)
  • 3 Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan. , (Japan)
  • 4 Department of Pathology, Fujita Health University, Toyoake, Japan. , (Japan)
  • 5 Laboratory of Molecular Biology, Fujita Health University Institute of Joint Research, Toyoake, Japan. , (Japan)
  • 6 Department of Pathology, School of Health Sciences, Fujita Health University, Toyoake, Japan. , (Japan)
  • 7 Department of Neurological Surgery, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
Type
Published Article
Journal
Neurosurgery
Publication Date
Aug 01, 2020
Volume
87
Issue
2
Pages
408–417
Identifiers
DOI: 10.1093/neuros/nyz524
PMID: 31833548
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The extent of resection has been reported to be associated with overall survival in gliomas. The use of 5-aminolevulinic acid (5-ALA) has been recognized to increase the extent of tumor resection. To evaluate what factors affect the intraoperative fluorescence after administration of 5-ALA in gliomas. Correlation of intraoperative fluorescence and several clinical, radiographic, molecular biologic, and histopathologic characters was retrospectively evaluated in 104 patients (53 males and 51 females; mean age 54.2 yr) with gliomas at our institution. To clarify the mechanisms that mutant isocitrate dehydrogenase (IDH) affect the intraoperative fluorescence, in Vitro experiments using genetically engineered glioma cells harboring mutant IDH1 were performed. Intraoperative fluorescence was observed in 82 patients (78.8%). In addition to age, magnetic resonance imaging enhancement, World Health Organization grades, and MIB-1 index, the status of IDH was revealed to be correlated with intraoperative fluorescence. In Vitro assay revealed that mutant IDH indirectly reduced the amount of exogenous 5-ALA-derived protoporphyrinogen IX in glioma cells by increasing activity of ferrochelatase and heme oxygenase 1. Mutant IDH1/2-induced metabolite changes of exogenous 5-ALA were suggested to contribute to the lesser intraoperative fluorescence in gliomas with mutant IDH1/2 than in those without. Copyright © 2019 by the Congress of Neurological Surgeons.

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