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

Shigeo Ohba, Kazuhiro Murayama, Kiyonori Kuwahara, Eriel Sandika Pareira, Shunsuke Nakae, Yuya Nishiyama, Kazuhide Adachi, Seiji Yamada, Hikaru Sasaki, Naoki Yamamoto, Masato Abe, Joydeep Mukherjee, Mitsuhiro Hasegawa, Russell O. Pieper, Yuichi Hirose

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

BACKGROUND: 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. OBJECTIVE: To evaluate what factors affect the intraoperative fluorescence after administration of 5-ALA in gliomas. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Original languageEnglish
Pages (from-to)408-417
Number of pages10
JournalNeurosurgery
Volume87
Issue number2
DOIs
Publication statusPublished - 2020 Aug 1

Keywords

  • 5-ALA
  • Ferrochelatase
  • Glioma
  • Heme oxygenase 1
  • IDH
  • PpIX

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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