title: Different glucose uptake and glycolytic mechanisms between hepatocellular carcinoma and intrahepatic mass-forming cholangiocarcinoma with increased (18)F-FDG uptake.
abstract: (18)F-FDG uptake in malignant tumors largely depends on the presence of facilitated glucose transporters, especially type 1 (Glut 1) and a rate-limiting glycolytic enzyme, hexokinase (HK) type II. Low expression of Glut 1 was reported in hepatocellular carcinoma (HCC), whereas high expression was found in cholangiocarcinoma. Immunohistochemistry and proteome analysis were performed to obtain a detailed evaluation of the mechanisms involved in glucose uptake and use in these tumors.
  
  
  METHODS
  Tumor tissues obtained from both HCC (n = 7) and mass-forming cholangiocarcinoma patients (n = 7) who showed increased (18)F-FDG uptake on PET were used. Immunohistochemistry for Glut 1 and HK I-III was performed in all tumor tissues. To identify proteins that regulate carbohydrate metabolism, a proteome analysis with matrix-assisted laser desorption ionization-time of flight and enzymatic digestion in-gel were performed using 8 available tumor samples and 3 normal liver tissues. Of the 8 tumor samples, 4 were HCCs; one was an intermediate phenotype HCC, and 3 were cholangiocarcinomas. The spot intensity of the proteins was calculated using proteome data; the tissues then were divided into 2 groups on the basis of the protein expression pattern, because the protein expression pattern of the intermediate-phenotype HCC was close to that of the cholangiocarcinomas. Group A included the HCCs and group B included the intermediate-phenotype HCC as well as the cholangiocarcinomas.
  
  
  RESULTS
  Immunoreactivity for Glut 1 was positive in all cholangiocarcinomas, but was negative in all HCCs except the one intermediate phenotype. However, HK II was positive in HCCs but was negative in 6 of the 7 cholangiocarcinomas. A total of 331 protein spots with a P value of <0.05 were identified by proteome analysis. Thirteen of these proteins that regulate carbohydrate metabolism were selected. The pentose phosphate pathway was increased in both groups, but more significantly in group B. Gluconeogenesis enzymes were decreased in both groups, but the tricarboxylic acid cycle-regulating enzyme expression was variable.
  
  
  CONCLUSIONS
  HCCs have different glucose-regulating mechanisms from those of cholangiocarcinomas, even though both tumors showed increased (18)F-FDG uptake on PET scans. Further studies are required with regard to energy metabolism and (18)F-FDG uptake patterns in association with various oncogenic alterations regulating multiple steps of the glycolytic pathways.
authors.affiliation: Division of Nuclear Medicine, Department of Diagnostic Radiology, Yonsei University College of Medicine, Seoul, Korea. jdlee@yumc.yonsei.ac.kr
authors.forename: Jong Doo
authors.initials: JD
authors.lastname: Lee
authors.forename: Woo Ick
authors.initials: WI
authors.lastname: Yang
authors.forename: Young Nyun
authors.initials: YN
authors.lastname: Park
authors.forename: Kyung Sik
authors.initials: KS
authors.lastname: Kim
authors.forename: Jin Sub
authors.initials: JS
authors.lastname: Choi
authors.forename: Mijin
authors.initials: M
authors.lastname: Yun
authors.forename: Dooheun
authors.initials: D
authors.lastname: Ko
authors.forename: Tae-Sung
authors.initials: TS
authors.lastname: Kim
authors.forename: Arthur E H
authors.initials: AE
authors.lastname: Cho
authors.forename: Hye Mi
authors.initials: HM
authors.lastname: Kim
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.forename: Seung-Soon
authors.initials: SS
authors.lastname: Im
authors.forename: Yong-Ho
authors.initials: YH
authors.lastname: Ahn
authors.forename: Chang Woon
authors.initials: CW
authors.lastname: Choi
authors.forename: Jeon Han
authors.initials: JH
authors.lastname: Park
mesh_terms: D001650:Bile Duct Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D001653:Bile Ducts, Intrahepatic / Q000000981:diagnostic imaging / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005947:Glucose / Q000493:pharmacokinetics*; D006019:Glycolysis; D006801:Humans; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose