O 6-methylguanine DNA methyltransferase and glucose transporter 2 in foregut and hindgut gastrointestinal neuroendocrine neoplasms

Hirofumi Watanabe, Yuto Yamazaki, Fumiyoshi Fujishima, Komoto Izumi, Masayuki Imamura, Susumu Hijioka, Kazuhiro Toriyama, Yasushi Yatabe, Atsushi Kudo, Fuyuhiko Motoi, Michiaki Unno, Hironobu Sasano

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Streptozocin (STZ) is used for treating both pancreatic (PanNET) and gastrointestinal (GI-NET) neuroendocrine tumors but its therapeutic efficacy is relatively low in GI-NETs. Therefore, it has become pivotal to select GI-NET patients who could benefit from STZ treatment. STZ is transported via the glucose transporter 2 (GLUT2) into the cells and the loss of O6-methylguanine DNA methyltransferase (MGMT) also increases its therapeutic efficacy. Therefore, GLUT2 high and MGMT low status could be the surrogate markers of STZ. Methods: In this study, we examined the MGMT and GLUT2 status in gastrointestinal neuroendocrine neoplasm (NEN). We studied 84 NEN cases: 33 foregut and 37 hindgut GI-NETs and 14 gastrointestinal neuroendocrine carcinomas (GI-NECs). Results: In GI-NETs, MGMT scores of ≥2 and ≥ 3 were 77% (54/70) and 56% (39/70), respectively, and GLUT2 scores of ≥4 and ≥ 6 were 30% (21/70) and 4.3% (3/70), respectively. Methylation-specific polymerase chain reaction revealed that MGMT promoter methylation was detected only in 2/14 GI-NECs but none of the included GI-NETs. GLUT2 (GLUT2 score) and MGMT immunoreactivity (MGMT and H-scores) were both significantly correlated with Ki-67 labeling index (GLUT2 score: P = 0.0045, ρ = − 0.4570; MGMT score: P = 0.0064, ρ = − 0.4399; H-score: P = 0.0110, ρ = − 0.4135) and MGMT immunoreactivity were significantly correlated with GLUT2 immunoreactivity (MGMT score: P = 0.0198; H-score, P = 0.0004, ρ = 0.5483) in hindgut NETs, but not in foregut NETs. However, discrepancies from the above correlation between GLUT2 and MGMT immunoreactivity were detected in several GI-NET cases which could be potential candidates for STZ therapy. Conclusion: The evaluation of MGMT and GLUT2 status could provide an important information in planning STZ therapy in GI-NET patients.

Original languageEnglish
Article number1195
JournalBMC Cancer
Volume20
Issue number1
DOIs
Publication statusPublished - 2020 Dec

Keywords

  • Glucose transporter 2
  • Immunohistochemistry
  • Neuroendocrine neoplasm
  • O-methylguanine DNA methyltransferase

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

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