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Published on: July 21, 2018
Hepatocyte nuclear factor 1α-inactivated hepatocellular adenomas exhibit high (18)F-fludeoxyglucose uptake associated
Kumi Ozaki1,2, Kenichi Harada3, Noboru Terayama1
11 Department of Radiology, Takaoka City Hospital, Takaoka, Japan.
Objective:
This immunohistochemical study aimed to elucidate the molecular mechanism underlying the increased fluorine-18 fludeoxyglucose (FDG) uptake in hepatocyte nuclear factor 1α (HNF1α)-inactivated hepatocellular adenomas (H-HCAs).
Methods:
Three resected H-HCAs were studied using FDG positron emission tomography. Each maximum standardized uptake value (SUVmax) was determined. Resected samples were subjected to immunohistochemical staining for the following glucose metabolism-related proteins: glucose transporter 1 (GLUT1) and glucose transporter 2 (GLUT2), indicative of uptake and transport of glucose into cellular cytoplasm; hexokinase 2 (HK2) and hexokinase 4 (HK4), glucose phosphorylation; glucose-6-phosphate transporter 1 (G6PT1), uptake and transport of glucose-6-phosphate into endoplasmic reticulum; and glucose-6-phosphatase (G6Pase), dephosphorylation.
Results:
All three H-HCAs exhibited increased FDG intake, with an average SUVmax of 6.6 (range: 5.2-8.2). No sample expressed GLUT1 and HK2; all the samples exhibited equivalent GLUT2 and HK4 expression, equivalent or slightly increased G6Pase expression and significantly decreased G6PT1 expression relative to the non-neoplastic hepatocytes of background liver.
Conclusion:
The increased FDG uptake observed in H-HCAs is associated with GLUT2 and HK4 expression and G6PT1 inactivation.
Advances In Knowledge:
H-HCA exhibits a high FDG uptake owing to the inactivation of G6PT1, which is transcriptionally regulated by HNF1α.
Insights
Hepatocellular adenomas with inactivated HNF1α show increased FDG uptake due to G6PT1 inactivation. This molecular change involves altered glucose metabolism proteins, impacting PET imaging.
Area of Science:
- Molecular mechanisms of liver disease
- Biochemistry of glucose metabolism
- Positron Emission Tomography (PET) imaging
Background:
- Hepatocellular adenomas (HCAs) are benign liver tumors.
- Hepatocyte nuclear factor 1α (HNF1α)-inactivated HCAs (H-HCAs) exhibit increased fluorine-18 fludeoxyglucose (FDG) uptake on PET scans.
- The underlying molecular mechanisms for this increased FDG uptake are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms responsible for elevated FDG uptake in H-HCAs.
- To investigate the expression of key glucose metabolism-related proteins in H-HCAs.
Main Methods:
- Immunohistochemical analysis of three resected H-HCAs.
- FDG Positron Emission Tomography (PET) to determine maximum standardized uptake value (SUVmax).
- Assessment of glucose transporters (GLUT1, GLUT2), hexokinases (HK2, HK4), glucose-6-phosphate transporter 1 (G6PT1), and glucose-6-phosphatase (G6Pase) expression.
Main Results:
- All studied H-HCAs showed increased FDG uptake (average SUVmax 6.6).
- Absence of GLUT1 and HK2 expression was observed.
- Equivalent GLUT2 and HK4 expression, similar or slightly increased G6Pase expression, and significantly decreased G6PT1 expression were found compared to normal hepatocytes.
Conclusions:
- Increased FDG uptake in H-HCAs is linked to the expression of GLUT2 and HK4, alongside G6PT1 inactivation.
- G6PT1 inactivation, transcriptionally regulated by HNF1α, drives high FDG uptake in H-HCAs.
