Different Glucose Uptake and Glycolytic Mechanisms Between Hepatocellular Carcinoma and Intrahepatic Mass-Forming Cholangiocarcinoma with Increased 18F-FDG Uptake

Different Glucose Uptake and Glycolytic Mechanisms Between Hepatocellular Carcinoma and Intrahepatic Mass-Forming Cholangiocarcinoma with Increased ¹⁸F-FDG Uptake

Jong Doo Lee, MD, PhD¹, Woo Ick Yang, MD, PhD², Young Nyun Park, MD, PhD², Kyung Sik Kim, MD, PhD³, Jin Sub Choi, MD, PhD³, Mijin Yun, MD¹, Dooheun Ko, MD¹, Tae-Sung Kim, MD¹, Arthur E.H. Cho, MD¹, Hye Mi Kim, MD, PhD¹, Kwang-Hyub Han, MD,PhD⁴, Seung-Soon Im, MS⁵, Yong-Ho Ahn, MD, PhD⁵, Chang Woon Choi, MD, PhD⁶ and Jeon Han Park, MD, PhD⁷

¹ Division of Nuclear Medicine, Department of Diagnostic Radiology, Yonsei University College of Medicine, Seoul, Korea
² Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
³ Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
⁴ Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
⁵ Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea
⁶ Department of Nuclear Medicine, Korea Cancer Center Hospital, Seoul, Korea
⁷ Department of Microbiology, Yonsei University College of Medicine, Seoul, Korea

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FIGURE 1. (A) Two-dimensional gel electrophoresis map of human liver tumor tissue demonstrates numerous protein spots. (B) Proteome analysis enables grouping of tumors (normal, HCC, and cholangiocarcinoma groups) as seen on distance tree mapping of protein expression profiles. However, protein expression pattern of intermediate phenotype of HCC group (patient 7) is close to cholangiocarcinoma group.

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FIGURE 2. Nodular HCC (Edmondson grade II–III) in right lobe of liver, inferior segment, shows increased ¹⁸F-FDG uptake on PET scan (patient 3). Immunohistochemical staining shows a negative reaction for Glut 1 but a positive reaction for HK II (x400).

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FIGURE 3. Mass-forming cholangiocarcinoma in right lobe of liver, inferior segment, shows intense ¹⁸F-FDG uptake (patient 10). Pathologically, tumor shows a strong positive reaction for Glut 1 along cell membrane but a negative reaction for HK II (x400).

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FIGURE 4. Mass with intense ¹⁸F-FDG uptake as seen in Figures 2 and 3 shows a positive reaction for both Glut 1 and HK II and, additionally, the biliary marker CK-19 (patient 7) (x400). Morphologically, lesion is classified as an HCC; however, biologically, it has both HCC and cholangiocarcinoma phenotypes.

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FIGURE 5. Protein expression level of glutathione peroxidase (GPO) and especially 6-phosphogluconolactonase (6-PGL) is increased in both HCC and cholangiocarcinomas, more in cholangiocarcinoma group. (Group A includes HCCs; group B includes intermediate phenotype of HCC and cholangiocarcinomas.).

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FIGURE 6. mRNA expression of glucose-6-phosphate dehydrogenase (G6PDH) is markedly increased in intermediate-phenotype HCC and cholangiocarcinomas (Cholangio) compared with normal and HCC.