Analysis of the Roles of Glucose Transporter 1 and Hexokinase 2 in the Metabolism of Glucose by Extrahepatic Bile Duct Cancer Cells

PURPOSE OF THE REPORT: Extrahepatic bile duct (EHD) cancer varies in uptake of FDG. The aim of the present study was to determine the role of glucose transporter (GLUT) 1 and hexokinase (HK) 2 in the glucose metabolism of EHD cancer cells using immunohistochemistry and F-FDG PET/CT. METHODS: Twenty-six patients with EHD cancer who underwent baseline PET/CT and surgery were studied. Biopsies were immunohistochemically analyzed using antibodies against GLUT1 and HK2, and the expression was scored from 0 to 4 according to the percentage of stained cells. SUV and tumor-to-liver ratio (T/Lratio) were obtained from F-FDG PET/CT data. SUV and T/Lratio and GLUT1 and HK2 expression were compared with histological grades and tumor locations (proximal and distal EHD) to correlate glucose metabolism with the expression of GLUT1 and HK2. RESULTS: SUV, T/Lratio, and GLUT1 and HK2 expression did not differ as a function of histological grade and tumor location. GLUT1 and HK2 were expressed in 20 (76.9%) and 22 (84.6%) of 26 tumor biopsies, respectively. The GLUT1 score, SUV, and T/Lratio increased, and the GLUT1 score, but not the HK2 score, correlated significantly with SUV (ρ = 0.648) and T/Lratio (ρ = 0.703). There was no direct correlation between the expression of GLUT1 and that of HK2 (ρ = 0.2046, P = 0.3161). CONCLUSIONS: Although GLUT1 and HK2 regulate intracellular accumulation of FDG in many cancers, only GLUT1 expression was correlated with FDG uptake by EHD cancers.