Glucose transporter 1 gene expression is related to thyroid neoplasms with an unfavorable prognosis: an immunohistochemical study.
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.
Schönberger
Johann
J
Department of Nuclear Medicine, University of Regensburg, Germany. johann.schoenberger@klinik.uni-regensburg.de
Rüschoff
J
J
Grimm
Daniela
D
Marienhagen
Jörg
J
Rümmele
Petra
P
Meyringer
Rotraud
R
Kossmehl
Peter
P
Hofstaedter
Ferdinand
F
Eilles
Christoph
C
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
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