title: Hepatocyte nuclear factor 1α-inactivated hepatocellular adenomas exhibit high (18)F-fludeoxyglucose uptake associated with glucose-6-phosphate transporter inactivation.
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.
  
  
  CONCLUSIONS
  The increased FDG uptake observed in H-HCAs is associated with GLUT2 and HK4 expression and G6PT1 inactivation.
  
  
  CONCLUSIONS
  H-HCA exhibits a high FDG uptake owing to the inactivation of G6PT1, which is transcriptionally regulated by HNF1α.
authors.affiliation: 1 Department of Radiology, Takaoka City Hospital, Takaoka, Japan.|Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Ozaki
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.affiliation: 1 Department of Radiology, Takaoka City Hospital, Takaoka, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Terayama
authors.affiliation: Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsui
authors.affiliation: Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saitoh
authors.affiliation: Department of Surgery, Toyonaka Municipal Hospital, Toyonaka, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Tomimaru
authors.affiliation: Department of Pathology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Gabata
mesh_terms: D018248:Adenoma, Liver Cell / Q000378:metabolism*; D000328:Adult; D017920:Antiporters / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012189:Retrospective Studies
chemical_list: D017920:Antiporters; D051538:Hepatocyte Nuclear Factor 1-alpha; D009004:Monosaccharide Transport Proteins; D019275:Radiopharmaceuticals; C111261:glucose 6-phosphate(transporter); D019788:Fluorodeoxyglucose F18