Hepatocyte nuclear factor 1α-inactivated hepatocellular adenomas exhibit high (18)F-fludeoxyglucose uptake associated with glucose-6-phosphate transporter inactivation.

Abstract

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). 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. 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. The increased FDG uptake observed in H-HCAs is associated with GLUT2 and HK4 expression and G6PT1 inactivation. H-HCA exhibits a high FDG uptake owing to the inactivation of G6PT1, which is transcriptionally regulated by HNF1α.