Correlation between in vivo 18F-FDG PET and immunohistochemical markers of glucose uptake and metabolism in pheochromocytoma and paraganglioma.

Autor:	van Berkel A; Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands., Rao JU; Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands Department of Laboratory Medicine, Laboratory of Genetic, Endocrine and Metabolic Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands., Kusters B; Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands Department of Pathology, Maastricht University Medical Centre, Maastricht, The Netherlands., Demir T; Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands Department of Laboratory Medicine, Laboratory of Genetic, Endocrine and Metabolic Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands., Visser E; Department of Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands., Mensenkamp AR; Department of Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands., van der Laak JA; Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands., Oosterwijk E; Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands., Lenders JW; Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands Department of Medicine and Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Dresden, Germany., Sweep FC; Department of Laboratory Medicine, Laboratory of Genetic, Endocrine and Metabolic Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands., Wevers RA; Department of Laboratory Medicine, Laboratory of Genetic, Endocrine and Metabolic Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands., Hermus AR; Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands., Langenhuijsen JF; Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands., Kunst DP; Department of Otolaryngology, Radboud University Medical Centre, Nijmegen, The Netherlands; and., Pacak K; Eunice Kennedy Shriver, NICHD, National Institutes of Health, Bethesda, Maryland., Gotthardt M; Department of Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands., Timmers HJ; Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands Henri.Timmers@radboudumc.nl.
Jazyk:	angličtina
Zdroj:	Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2014 Aug; Vol. 55 (8), pp. 1253-9. Date of Electronic Publication: 2014 Jun 12.
DOI:	10.2967/jnumed.114.137034
Abstrakt:	Unlabelled: Pheochromocytomas and paragangliomas (PPGLs) can be localized by (18)F-FDG PET. The uptake is particularly high in tumors with an underlying succinate dehydrogenase (SDH) mutation. SDHx-related PPGLs are characterized by compromised oxidative phosphorylation and a pseudohypoxic response, which mediates an increase in aerobic glycolysis, also known as the Warburg effect. The aim of this study was to explore the hypothesis that increased uptake of (18)F-FDG in SDHx-related PPGLs is reflective of increased glycolytic activity and is correlated with expression of different proteins involved in glucose uptake and metabolism through the glycolytic pathway. Methods: Twenty-seven PPGLs collected from patients with hereditary mutations in SDHB (n = 2), SDHD (n = 3), RET (n = 5), neurofibromatosis 1 (n = 1), and myc-associated factor X (n = 1) and sporadic patients (n = 15) were investigated. Preoperative (18)F-FDG PET/CT studies were analyzed; mean and maximum standardized uptake values (SUVs) in manually drawn regions of interest were calculated. The expression of proteins involved in glucose uptake (glucose transporters types 1 and 3 [GLUT-1 and -3, respectively]), phosphorylation (hexokinases 1, 2, and 3 [HK-1, -2, and -3, respectively]), glycolysis (monocarboxylate transporter type 4 [MCT-4]), and angiogenesis (vascular endothelial growth factor [VEGF], CD34) were examined in paraffin-embedded tumor tissues using immunohistochemical staining with peroxidase-catalyzed polymerization of diaminobenzidine as a read-out. The expression was correlated with corresponding SUVs. Results: Both maximum and mean SUVs for SDHx-related tumors were significantly higher than those for sporadic and other hereditary tumors (P < 0.01). The expression of HK-2 and HK-3 was significantly higher in SDHx-related PPGLs than in sporadic PPGLs (P = 0.022 and 0.025, respectively). The expression of HK-2 and VEGF was significantly higher in SDHx-related PPGLs than in other hereditary PPGLs (P = 0.039 and 0.008, respectively). No statistical differences in the expression were observed for GLUT-1, GLUT-3, and MCT-4. The percentage anti-CD 34 staining and mean vessel perimeter were significantly higher in SDHx-related PPGLs than in sporadic tumors (P = 0.050 and 0.010, respectively). Mean SUVs significantly correlated with the expression of HK-2 (P = 0.027), HK-3 (P = 0.013), VEGF (P = 0.049), and MCT-4 (P = 0.020). Conclusion: The activation of aerobic glycolysis in SDHx-related PPGLs is associated with increased (18)F-FDG accumulation due to accelerated glucose phosphorylation by hexokinases rather than increased expression of glucose transporters. (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)
Databáze:	MEDLINE
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