title: Proliferative activity in hepatocellular carcinoma is closely correlated with glucose metabolism but not angiogenesis.
abstract: OBJECTIVE
  This study investigated the relationship between tumor proliferative activity and the grade of tumor glucose metabolism or angiogenesis in hepatocellular carcinoma (HCC).
  
  
  METHODS
  The study was performed as a retrospective analysis of 63 patients with HCC who underwent fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) as a preoperative examination prior to liver resection. Tumor proliferative activity was evaluated by the Ki-67 labeling index (LI). The grade of tumor glucose metabolism was evaluated by measuring the protein expression level of glucose transporter (GLUT)-1, expression level of pyruvate kinase type M2 (PKM2) mRNA, and FDG uptake. The grade of tumor angiogenesis was evaluated by the protein expression level of vascular endothelial growth factor (VEGF) and tumor microvessel density.
  
  
  RESULTS
  All patients were divided into tertiles according to the Ki-67 LI: the low LI group (n = 21), the intermediate LI group (n = 21), and the high LI group (n = 21). The high LI group showed a tendency to have advanced tumor stage, and lower disease-free survival and overall survival rates than the low LI and the intermediate LI groups. The expression grade of GLUT-1, PKM2 mRNA, and FDG uptake gradually increased with the Ki-67 LI. On the other hand, the protein expression grade of VEGF and microvessel density was paradoxically decreased with the Ki-67 LI.
  
  
  CONCLUSIONS
  These data suggest that (1) the proliferative activity of a resected specimen predicted the prognosis in patients with HCC; (2) the proliferative activity was closely correlated with the glucose metabolism, but not with angiogenesis.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kitamura
authors.forename: Etsuro
authors.initials: E
authors.lastname: Hatano
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Higashi
authors.forename: Masato
authors.initials: M
authors.lastname: Narita
authors.forename: Satoru
authors.initials: S
authors.lastname: Seo
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamoto
authors.forename: Kenya
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nagata
authors.forename: Kojiro
authors.initials: K
authors.lastname: Taura
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yasuchika
authors.forename: Takashi
authors.initials: T
authors.lastname: Nitta
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology*; D002455:Cell Division / Q000502:physiology; D005260:Female; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011379:Prognosis; D011770:Pyruvate Kinase / Q000235:genetics / Q000378:metabolism; D011877:Radionuclide Imaging; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D051272:Glucose Transporter Type 1; D019394:Ki-67 Antigen; C495677:SLC2A1 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D011770:Pyruvate Kinase