title: Glucose transporter 1 gene expression is related to thyroid neoplasms with an unfavorable prognosis: an immunohistochemical study.
abstract: OBJECTIVE
  An accelerated rate of glucose metabolism mediated by overexpression of key regulatory glycolytic enzymes and glucose transporters is among the most characteristic biochemical marker of malignant transformed cells. In thyroid neoplasms, however, an increased uptake of glucose [measured by 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET)] seems to be restricted to more aggressive and high-grade tumors, whereas tumors with favorable prognosis demonstrate no significant tracer uptake. We therefore studied the expression of glucose transporters in thyroid carcinomas with different grades of malignancy.
  
  
  METHODS
  Sections of formalin-fixed and paraffin-embedded tissue obtained from 45 patients with thyroid cancer (5 anaplastic, 20 papillary and 20 follicular tumors) were investigated. Polyclonal rabbit antiglucose transporter antibodies, reactive with glucose transporters 1-5 (GLUT1-5), were used after heat pretreatment of the sections. Staining was performed by the avidin-biotin conjugate immunoperoxidase reaction and evaluated semiquantitatively.
  
  
  RESULTS
  Expression of GLUT1 transporter on the cell membrane was closely related to the grade of malignancy in thyroid neoplasms (Fisher exact test p < 0.05). All anaplastic tumors showed a high level of GLUT1 expression in the cytoplasm and on the cell membrane. Positive membranous staining in differentiated tumors was detected predominantly in neoplasms with unfavorable prognosis, e.g., in widely invasive follicular or metastatic tumors, whereas low or no immunoreactivity could be seen in well-differentiated tumors or in normal thyroid epithelium.
  
  
  CONCLUSIONS
  These data indicate that overexpression of GLUT1 on the cell membrane of thyroid neoplasms is closely related to tumors demonstrating a more aggressive biological behavior. Therefore, determination of GLUT1 expression in thyroid cancer tissue may be a prognostic marker, and FDG-PET may be a helpful technique in identifying patients at a higher risk.
authors.affiliation: Department of Nuclear Medicine, University of Regensburg, Germany. johann.schoenberger@klinik.uni-regensburg.de
authors.forename: Johann
authors.initials: J
authors.lastname: Schönberger
authors.forename: J
authors.initials: J
authors.lastname: Rüschoff
authors.forename: Daniela
authors.initials: D
authors.lastname: Grimm
authors.forename: Jörg
authors.initials: J
authors.lastname: Marienhagen
authors.forename: Petra
authors.initials: P
authors.lastname: Rümmele
authors.forename: Rotraud
authors.initials: R
authors.lastname: Meyringer
authors.forename: Peter
authors.initials: P
authors.lastname: Kossmehl
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstaedter
authors.forename: Christoph
authors.initials: C
authors.lastname: Eilles
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D027342:Excitatory Amino Acid Transporter 2 / Q000032:analysis* / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D051273:Glucose Transporter Type 2; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D051296:Glucose Transporter Type 5; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000737:chemistry* / Q000401:mortality* / Q000503:physiopathology
chemical_list: D014408:Biomarkers, Tumor; D027342:Excitatory Amino Acid Transporter 2; D051273:Glucose Transporter Type 2; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D051296:Glucose Transporter Type 5; D019394:Ki-67 Antigen; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C495687:SLC2A3 protein, human; C495692:SLC2A4 protein, human