Kumi Ozaki1,2, Kenichi Harada3, Noboru Terayama1, Osamu Matsui2, Satoshi Saitoh4, Yoshito Tomimaru5, Takeshi Fujii6, Toshifumi Gabata2. 1. 1 Department of Radiology, Takaoka City Hospital, Takaoka, Japan. 2. Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan. 3. Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan. 4. Department of Hepatology, Toranomon Hospital, Tokyo, Japan. 5. Department of Surgery, Toyonaka Municipal Hospital, Toyonaka, Japan. 6. Department of Pathology, Toranomon Hospital, Tokyo, Japan.
Abstract
OBJECTIVE: This immunohistochemical study aimed to elucidate the molecular mechanism underlying the increased fluorine-18 fludeoxyglucose (FDG) uptake in hepatocyte nuclear factor 1α (HNF1α)-inactivated hepatocellular adenomas (H-HCAs). METHODS: Three resected H-HCAs were studied using FDG positron emission tomography. Each maximum standardized uptake value (SUVmax) was determined. Resected samples were subjected to immunohistochemical staining for the following glucose metabolism-related proteins: glucose transporter 1 (GLUT1) and glucose transporter 2 (GLUT2), indicative of uptake and transport of glucose into cellular cytoplasm; hexokinase 2 (HK2) and hexokinase 4 (HK4), glucose phosphorylation; glucose-6-phosphate transporter 1 (G6PT1), uptake and transport of glucose-6-phosphate into endoplasmic reticulum; and glucose-6-phosphatase (G6Pase), dephosphorylation. RESULTS: All three H-HCAs exhibited increased FDG intake, with an average SUVmax of 6.6 (range: 5.2-8.2). No sample expressed GLUT1 and HK2; all the samples exhibited equivalent GLUT2 and HK4 expression, equivalent or slightly increased G6Pase expression and significantly decreased G6PT1 expression relative to the non-neoplastic hepatocytes of background liver. CONCLUSION: The increased FDG uptake observed in H-HCAs is associated with GLUT2 and HK4 expression and G6PT1 inactivation. ADVANCES IN KNOWLEDGE: H-HCA exhibits a high FDG uptake owing to the inactivation of G6PT1, which is transcriptionally regulated by HNF1α.
OBJECTIVE: This immunohistochemical study aimed to elucidate the molecular mechanism underlying the increased fluorine-18 fludeoxyglucose (FDG) uptake in hepatocyte nuclear factor 1α (HNF1α)-inactivated hepatocellular adenomas (H-HCAs). METHODS: Three resected H-HCAs were studied using FDG positron emission tomography. Each maximum standardized uptake value (SUVmax) was determined. Resected samples were subjected to immunohistochemical staining for the following glucose metabolism-related proteins: glucose transporter 1 (GLUT1) and glucose transporter 2 (GLUT2), indicative of uptake and transport of glucose into cellular cytoplasm; hexokinase 2 (HK2) and hexokinase 4 (HK4), glucose phosphorylation; glucose-6-phosphate transporter 1 (G6PT1), uptake and transport of glucose-6-phosphate into endoplasmic reticulum; and glucose-6-phosphatase (G6Pase), dephosphorylation. RESULTS: All three H-HCAs exhibited increased FDG intake, with an average SUVmax of 6.6 (range: 5.2-8.2). No sample expressed GLUT1 and HK2; all the samples exhibited equivalent GLUT2 and HK4 expression, equivalent or slightly increased G6Pase expression and significantly decreased G6PT1 expression relative to the non-neoplastic hepatocytes of background liver. CONCLUSION: The increased FDG uptake observed in H-HCAs is associated with GLUT2 and HK4 expression and G6PT1 inactivation. ADVANCES IN KNOWLEDGE: H-HCA exhibits a high FDG uptake owing to the inactivation of G6PT1, which is transcriptionally regulated by HNF1α.
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