Expression of glucose transporters and hexokinase II in cholangiocellular carcinoma compared using [18F]‐2‐fluro‐2‐deoxy‐d‐glucose positron emission tomography

Abstract

Cholangiocellular carcinoma (CCC) has been reported to have a high glucose uptake; however, the mechanism of glucose entry into these cells is still unclear. We investigated the relationship between [(18)F]-2-fluro-2-deoxy-D-glucose ((18)F-FDG) uptake and the expression of facilitative glucose transporters (Glut) and hexokinase (HK) II, as well as the association between the expression of different histological types of CCC. The expression of Glut (1-5) and HK II was studied using immunohistochemistry of 26 patients with CCC who underwent whole-body (18)F-FDG positron emission tomography before surgery or biopsy. CCC expressed immunohistochemically detectable Glut 1 in 81%, Glut 2 in 54%, Glut 3 in 19%, and HK II in 77% of the total cases. Glut 1, Glut 2, Glut 3, and HK II were more often detected in moderately differentiated and poorly differentiated than in well-differentiated CCC. A significant correlation was observed between (18)F-FDG uptake and the staining scores of Glut 1 and HK II (P = 0.02, rho = 0.45 and P = 0.001, rho = 0.59). The staining scores of Glut 1 and HK II were also significantly correlated (P = 0.002, rho = 0.3). Multivariate regression analysis revealed that lymph-node metastasis was independently associated with (18)F-FDG uptake. Our study showed a significant association between the expression of Glut 1 and HK II with (18)F-FDG uptake, indicating that Glut 1 is a major glucose transporter expressed in CCC and that HK II contributes to the increased metabolism of glucose, especially in moderately and poorly differentiated CCC.