title: Gene Expression of Glucose Transporter 1 (GLUT1), Hexokinase 1 and Hexokinase 2 in Gastroenteropancreatic Neuroendocrine Tumors: Correlation with F-18-fluorodeoxyglucose Positron Emission Tomography and Cellular Proliferation.
abstract: Neoplastic tissue exhibits high glucose utilization and over-expression of glucose transporters (GLUTs) and hexokinases (HKs), which can be imaged by (18)F-Fluorodeoxyglucose-positron emission tomography (FDG-PET). The aim of the present study was to investigate the expression of glycolysis-associated genes and to compare this with FDG-PET imaging as well as with the cellular proliferation index in two cancer entities with different malignant potential. Using real-time PCR, gene expression of GLUT1, HK1 and HK2 were studied in 34 neuroendocrine tumors (NETs) in comparison with 14 colorectal adenocarcinomas (CRAs). The Ki67 proliferation index and, when available, FDG-PET imaging was compared with gene expression. Overexpression of GLUT1 gene expression was less frequent in NETs (38%) compared to CRAs (86%), P = 0.004. HK1 was overexpressed in 41% and 71% of NETs and CRAs, respectively (P = 0.111) and HK2 was overexpressed in 50% and 64% of NETs and CRAs, respectively (P = 0.53). There was a significant correlation between the Ki67 proliferation index and GLUT1 gene expression for the NETs (R = 0.34, P = 0.047), but no correlation with the hexokinases. FDG-PET identified foci in significantly fewer NETs (36%) than CRAs (86%), (P = 0.04). The gene expression results, with less frequent GLUT1 and HK1 upregulation in NETs, confirmed the lower metabolic activity of NETs compared to the more aggressive CRAs. In accordance with this, fewer NETs were FDG-PET positive compared to CRA tumors and FDG uptake correlated with GLUT1 gene expression.
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet & Cluster for Molecular Imaging, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen O, Denmark. tinbin@sund.ku.dk.
authors.forename: Tina
authors.initials: T
authors.lastname: Binderup
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet & Cluster for Molecular Imaging, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen O, Denmark. Ulrich.peter.knigge@regionh.dk.|Department of Surgical Gastroenterology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen O, Denmark. Ulrich.peter.knigge@regionh.dk.
authors.forename: Ulrich Peter
authors.initials: UP
authors.lastname: Knigge
authors.affiliation: Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen O, Denmark. birgitte.federspiel.01@regionh.dk.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Federspiel
authors.affiliation: Department of Urology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen O, Denmark. peter.sommer@regionh.dk.
authors.forename: Peter
authors.initials: P
authors.lastname: Sommer
authors.affiliation: Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen O, Denmark. jane.preuss.hasselby@regionh.dk.
authors.forename: Jane Preuss
authors.initials: JP
authors.lastname: Hasselby
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet & Cluster for Molecular Imaging, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen O, Denmark. Annika.loft.jakobsen@regionh.dk.
authors.forename: Annika
authors.initials: A
authors.lastname: Loft
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet & Cluster for Molecular Imaging, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen O, Denmark. akjaer@sund.ku.dk.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjaer
keywords: FDG-PET; gene expression; glucose; imaging; neuroendocrine tumors; proliferation index
references.citation: N Engl J Med. 2009 Jul 2;361(1):32-9
references.pmid: 19571281
references.citation: J Nucl Med. 1999 Apr;40(4):556-65
references.pmid: 10210213
references.citation: Clin Cancer Res. 2010 Feb 1;16(3):978-85
references.pmid: 20103666
references.citation: JAMA. 2007 Jan 17;297(3):267-77
references.pmid: 17227978
references.citation: Dis Colon Rectum. 2007 Jan;50(1):102-14
references.pmid: 17115340
references.citation: Dig Dis Sci. 2006 Dec;51(12 ):2198-205
references.pmid: 17080242
references.citation: J Nucl Med. 2004 Jan;45(1):22-9
references.pmid: 14734665
references.citation: Hematol Oncol. 2006 Sep;24(3):146-50
references.pmid: 16729353
references.citation: Dis Colon Rectum. 2000 Jun;43(6):759-67; discussion 767-70
references.pmid: 10859074
references.citation: J Nucl Med. 2005 Oct;46(10 ):1753-9
references.pmid: 16204727
references.citation: J Nucl Med. 2010 May;51(5):704-12
references.pmid: 20395333
references.citation: Lung Cancer. 2008 Jul;61(1):54-60
references.pmid: 18191496
references.citation: Haematologica. 2006 Apr;91(4):482-9
references.pmid: 16585015
references.citation: Neuroendocrinology. 2009;90(2):162-6
references.pmid: 19060454
references.citation: Endocr Relat Cancer. 2005 Dec;12(4):1083-92
references.pmid: 16322345
references.citation: Eur J Nucl Med. 2000 Dec;27(12):1778-85
references.pmid: 24578007
references.citation: Cancer. 2008 Jun;112(11):2447-55
references.pmid: 18383518
references.citation: Cancer Res. 1999 Sep 15;59(18):4709-14
references.pmid: 10493529
references.citation: Cancer Imaging. 2006 Oct 31;6:S71-81
references.pmid: 17114081
references.citation: Hepatogastroenterology. 2005 Mar-Apr;52(62):486-90
references.pmid: 15816463
references.citation: J Nucl Med. 2005 Apr;46(4):675-82
references.pmid: 15809491
references.citation: Acta Oncol. 2004;43(7):617-25
references.pmid: 15545182
references.citation: AJR Am J Roentgenol. 2009 Apr;192(4):W156-60
references.pmid: 19304675
references.citation: Oncogene. 2006 Aug 7;25(34):4777-86
references.pmid: 16892090
references.citation: Endocr Relat Cancer. 2008 Dec;15(4):1083-97
references.pmid: 18603570
references.citation: Neuroendocrinology. 2008;87(4):223-32
references.pmid: 18196892
references.citation: N Engl J Med. 2004 Mar 18;350(12):1200-10
references.pmid: 15028824
references.citation: Acta Radiol. 2008 Dec;49(10):1145-53
references.pmid: 18979289
references.citation: Ann Surg. 1999 Jun;229(6):815-21; discussion 822-3
references.pmid: 10363895
references.citation: CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66
references.pmid: 17237035