NDLI: O6-methylguanine DNA methyltransferase and glucose transporter 2 in foregut and hindgut gastrointestinal neuroendocrine neoplasms

Content Provider	Springer Nature : BioMed Central
Author	Watanabe, Hirofumi Yamazaki, Yuto Fujishima, Fumiyoshi Izumi, Komoto Imamura, Masayuki Hijioka, Susumu Toriyama, Kazuhiro Yatabe, Yasushi Kudo, Atsushi Motoi, Fuyuhiko Unno, Michiaki Sasano, Hironobu
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.
Related Links	https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-020-07579-6.pdf
Ending Page	14
Page Count	14
Starting Page	1
File Format	HTM / HTML
ISSN	14712407
DOI	10.1186/s12885-020-07579-6
Journal	BMC Cancer
Issue Number	1
Volume Number	20
Language	English
Publisher	BioMed Central
Publisher Date	2020-12-07
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Health Promotion and Disease Prevention Biomedicine Medicine Public Health Neuroendocrine neoplasm O6-methylguanine DNA methyltransferase Glucose transporter 2 Immunohistochemistry Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology Genetics
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.8/2023

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