Molecular mechanisms of [18F]fluorodeoxyglucose accumulation in liver cancer

Izuishi,Kunihiko; Yamamoto,Yuka; Mori,Hirohito; Kameyama,Riko; Fujihara,Shintaro; Masaki,Tsutomu; Suzuki,Yasuyuki

doi:10.3892/or.2013.2886

Molecular mechanisms of [18F]fluorodeoxyglucose accumulation in liver cancer

Authors:
- Kunihiko Izuishi
- Yuka Yamamoto
- Hirohito Mori
- Riko Kameyama
- Shintaro Fujihara
- Tsutomu Masaki
- Yasuyuki Suzuki
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Affiliations: Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Miki, Kita, Kagawa 761-0793, Japan, Department of Radiology, Faculty of Medicine, Kagawa University, Miki, Kita, Kagawa 761-0793, Japan, Department of Internal Medicine of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kita, Kagawa 761-0793, Japan
Published online on: November 29, 2013 https://doi.org/10.3892/or.2013.2886
Pages: 701-706

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Abstract

To elucidate the molecular mechanisms underlying the insufficient sensitivity in the detection of hepatocellular carcinoma (HCC) by [18F] 2-ﬂuoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), the characteristics of glucose metabolism-related protein expression in HCC were examined in liver metastasis from colorectal cancer (Meta). Thirty-four patients (14 Meta and 20 HCC) who underwent FDG-PET and hepatectomy were studied. The relationships between the maximum standardized uptake value (SUV) in tumors and the mRNA expression of glucose metabolism-related proteins [hexokinase (HK), glucose transporter 1 (GLUT1), and glucose-6-phosphatase (G6Pase)] and proliferating cell nuclear antigen (PCNA) were examined in snap-frozen specimens with quantitative PCR. Tumor detection rates were lower in HCC (15/20) compared to Meta (13/14) patients. HK and GLUT1 expression was lower and G6Pase expression was higher in HCC compared to Meta. In particular, GLUT1 overexpression was 92-fold in Meta and 11-fold in HCC compared to the surrounding liver. The SUV correlated with GLUT1 and PCNA expression in HCC, but not Meta patients. Of note, four cases of poorly differentiated (P/D) HCC compared to moderately differentiated (M/D) HCC produced completely different results for FDG uptake (SUV, 14.4 vs. 4.0) and mRNA expression (G6Pase expression, 0.007 vs. 1.5). Variations in the expression of glucose metabolism-related enzymes between HCC and Meta patients are attributed to origin or degree of differentiation. Low FDG uptake in M/D HCC reflected low GLUT1 and high G6Pase expression, while high FDG accumulation in P/D HCC could reflect increased GLUT1 and decreased G6Pase expression. These results may explain why M/D HCC is not detected as sensitively by FDG-PET.

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