Different glucose uptake and glycolytic mechanisms between hepatocellular carcinoma and intrahepatic mass-forming cholangiocarcinoma with increased 18F-FDG uptake

Jong Doo Lee, Woo Ick Yang, Young Nyun Park, Kyung Sik Kim, Jin Sub Choi, Mijin Yun, Dooheun Ko, Tae Sung Kim, Arthur E.H. Cho, Hye Mi Kim, Kwang Hyub Han, Seung Soon Im, Yong Ho Ahn, Chang Woon Choi, Jeon Han Park

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Abstract

18F-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 18F-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. Conclusion: HCCs have different glucose-regulating mechanisms from those of cholangiocarcinomas, even though both tumors showed increased 18F-FDG uptake on PET scans. Further studies are required with regard to energy metabolism and 18F-FDG uptake patterns in association with various oncogenic alterations regulating multiple steps of the glycolytic pathways.

Original languageEnglish
Pages (from-to)1753-1759
Number of pages7
JournalJournal of Nuclear Medicine
Volume46
Issue number10
Publication statusPublished - 2005 Oct 1

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging

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    Lee, J. D., Yang, W. I., Park, Y. N., Kim, K. S., Choi, J. S., Yun, M., Ko, D., Kim, T. S., Cho, A. E. H., Kim, H. M., Han, K. H., Im, S. S., Ahn, Y. H., Choi, C. W., & Park, J. H. (2005). Different glucose uptake and glycolytic mechanisms between hepatocellular carcinoma and intrahepatic mass-forming cholangiocarcinoma with increased 18F-FDG uptake. Journal of Nuclear Medicine, 46(10), 1753-1759.