Proliferative activity in hepatocellular carcinoma is closely correlated with glucose metabolism but not angiogenesis

• Published in: Journal of hepatology Vol. 55; no. 4; pp. 846 - 857
• Main Authors: Kitamura, Koji, Hatano, Etsuro, Higashi, Tatsuya, Narita, Masato, Seo, Satoru, Nakamoto, Yuji, Yamanaka, Kenya, Nagata, Hiromitsu, Taura, Kojiro, Yasuchika, Kentaro, Nitta, Takashi, Uemoto, Shinji
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01-10-2011; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biopsy; Blood Glucose - metabolism; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - physiopathology; Cell Division - physiology; Female; Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET); Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Glucose Transporter Type 1 - genetics; Glucose Transporter Type 1 - metabolism; Glucose transporter-1 (GLUT-1); Humans; Kaplan-Meier Estimate; Ki-67 Antigen - metabolism; Liver Neoplasms - metabolism; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Liver Neoplasms - physiopathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Micro vessel density; Middle Aged; Neovascularization, Pathologic - diagnostic imaging; Neovascularization, Pathologic - physiopathology; Prognosis; Pyruvate Kinase - genetics; Pyruvate Kinase - metabolism; Pyruvate kinase type M2 (PKM2); Radionuclide Imaging; Retrospective Studies; Tumors; Vascular endothelial growth factor (VEGF); Vascular Endothelial Growth Factor A - metabolism; FDG-PET; CRP; 18F-fluorodeoxyglucose positron emission tomography; magnetic resonance imaging; Pyruvate kinase type M2 (PKM2); C-reactive protein; MRI; Vascular endothelial growth factor (VEGF); AFP; tumor to non-tumor ratio of SUV; pyruvate kinase type M2; GLUT-1; Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET); labeling index; TNR; α-fetoprotein; hepatocellular carcinoma; computed tomography; PKM2; VEGF; CI; microvessel density; HCC; standardized uptake value; des-gamma carboxy prothrombin; DCP; CT; SUV; Micro vessel density; vascular endothelial growth factor; MVD; confidence interval; glucose transporter-1; LI; Glucose transporter-1 (GLUT-1); Radionuclide study; 2-deoxy-2-fluoroglucose; Fluorine; Hepatic disease; Hepatocellular carcinoma; Glucose; Density; Angiogenesis; Blood vessel; Gastroenterology; Enzyme; Transferases; Pyruvate; Malignant tumor; Metabolism; Vascular endothelium growth factor; Kinase; Digestive diseases; Positron emission tomography; Cancer; Emission tomography
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2011.01.038

Background & Aims 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.