Clinicopathologic Features and Molecular Characteristics of Glucose Metabolism Contributing to ¹⁸F-fluorodeoxyglucose Uptake in Gastrointestinal Stromal Tumors.
Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) is useful in the preoperative diagnosis of gastrointestinal stromal tumors (GISTs); however, the molecular characteristics of glucose metabolism of GIST are unknown. We evaluated 18F-FDG uptake on preoperative PET/CT of 40 patients and analyzed the expression of glycolytic enzymes in resected GIST tissues by qRT-PCR, western blotting, and immunohistochemistry. Results of receiver operating characteristic curve analysis showed that the maximum standardized uptake value (SUVmax) cut-off value of 4.99 had a sensitivity of 89.5%, specificity was 76.2%, and accuracy of 82.5% for identifying tumors with a high risk of malignancy. We found that 18F-FDG uptake correlated positively with tumor size, risk grade, and expression levels of glucose transporter 1 (GLUT1), hexokinase 1 (HK1), and lactate dehydrogenase A (LDHA). Elevated HK and LDH activity was found in high-risk tumors. Among the isoforms of GLUT and HK, GLUT1 and HK1 expression increased with higher tumor risk grade. In addition, overexpression of glycolytic enzymes M2 isoform of pyruvate kinase (PKM2) and LDHA was observed in GISTs, especially in high-risk tumors. These results suggest that upregulation of GLUT1, HK1, PKM2, and LDHA may play an important role in GIST tumorigenesis and may be useful in the preoperative prediction of malignant potential.
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Min-Hee
MH
Cho
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Cheol Keun
CK
Park
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Minhee
M
Park
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Won Kyu
WK
Kim
Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Arthur
A
Cho
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Hoguen
H
Kim
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D049268:Positron-Emission Tomography / Q000379:methods; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden; D055815:Young Adult; D000097810:Thyroid Hormone-Binding Proteins
D015415:Biomarkers; D002352:Carrier Proteins; D019788:Fluorodeoxyglucose F18; D005947:Glucose; D051272:Glucose Transporter Type 1; D006593:Hexokinase; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D008565:Membrane Proteins; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C472074:HK1 protein, human