Skip to main content
Top
Published in: European Journal of Nuclear Medicine and Molecular Imaging 1/2004

01-01-2004 | Original Article

Expression of Glut-1 and Glut-3 in untreated oral squamous cell carcinoma compared with FDG accumulation in a PET study

Authors: Mei Tian, Hong Zhang, Yoshiki Nakasone, Kenji Mogi, Keigo Endo

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 1/2004

Login to get access

Abstract

Increased expression of glucose transporter-1 (Glut-1) and glucose transporter-3 (Glut-3) has been reported in many human cancers. The mechanism of glucose entry into oral squamous cell carcinoma (OSCC) remains unclear. In this study we investigated, in untreated human OSCC, the relationship between tumour fluorine-18 fluoro-2-deoxy-d-glucose (FDG) accumulation and the expression of Glut-1 and Glut-3, as well as the association between the expression of Glut-1 and of Glut-3. All patients underwent FDG positron emission tomography (PET) pre-operatively. Standardised uptake values (SUVs) were used for evaluation of tumour FDG uptake. Final diagnoses were established by histology. Immunohistochemical staining results were evaluated according to the percentage (%) of positive area, intensity and staining score. Tumour sections were stained by immunohistochemistry for Glut-1 and Glut-3. Glut-1 immunostaining revealed that 18 (94.7%) of the 19 tumours stained positively, while Glut-3 immunostaining yielded positive findings for 16 (84.2%) tumours. Overall, a relatively low level of agreement (36.8%) in the staining score was observed between Glut-1 and Glut-3 expression. No relationship was found between the staining pattern and tumour differentiation or T grade classification in either Glut-1 or Glut-3 immunostaining. Furthermore, no relationship was found between increased FDG SUV and tumour differentiation, but the former did correlate with T grade. In conclusion, high FDG uptake values were seen in OSCC with overexpression of Glut-1 and Glut-3. However, no significant correlation was found between FDG SUV and Glut-1 or Glut-3 expression.
Literature
1.
go back to reference Ak I, Stokkel MP, Pauwels EK. Positron emission tomography with 2-[18F]fluoro-2-deoxy-d-glucose in oncology. Part II. The clinical value in detecting and staging primary tumours. J Cancer Res Clin Oncol 2000; 126:560–574.PubMed Ak I, Stokkel MP, Pauwels EK. Positron emission tomography with 2-[18F]fluoro-2-deoxy-d-glucose in oncology. Part II. The clinical value in detecting and staging primary tumours. J Cancer Res Clin Oncol 2000; 126:560–574.PubMed
2.
go back to reference Warburg O, Posenser K, Negelein E. The metabolism of the carcinoma cell. In: The metabolism of tumors. New York: Richard R. Smith; 1931:129–169. Warburg O, Posenser K, Negelein E. The metabolism of the carcinoma cell. In: The metabolism of tumors. New York: Richard R. Smith; 1931:129–169.
3.
go back to reference Isselbacher K. Sugar and amino acid transport by cells in culture—differences between normal and malignant cells. N Engl J Med 1972; 286:929–933. Isselbacher K. Sugar and amino acid transport by cells in culture—differences between normal and malignant cells. N Engl J Med 1972; 286:929–933.
4.
go back to reference Stokkel MP, Linthorst MF, Borm JJ, Taminiau AH, Pauwels EK. A reassessment of bone scintigraphy and commonly tested pretreatment biochemical parameters in newly diagnosed osteosarcoma. J Cancer Res Clin Oncol 2002; 128:393–399.CrossRefPubMed Stokkel MP, Linthorst MF, Borm JJ, Taminiau AH, Pauwels EK. A reassessment of bone scintigraphy and commonly tested pretreatment biochemical parameters in newly diagnosed osteosarcoma. J Cancer Res Clin Oncol 2002; 128:393–399.CrossRefPubMed
5.
go back to reference Stuart Wood I, Trayhurn P. Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 2003; 89:3–9.PubMed Stuart Wood I, Trayhurn P. Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins. Br J Nutr 2003; 89:3–9.PubMed
6.
go back to reference Oehr P, Ruhlmann J, Biersack HJ. FDG-PET in clinical oncology: review of the literature and report of one institution’s experience. J Investig Med 1999; 47:452–461.PubMed Oehr P, Ruhlmann J, Biersack HJ. FDG-PET in clinical oncology: review of the literature and report of one institution’s experience. J Investig Med 1999; 47:452–461.PubMed
7.
go back to reference Yamamoto T, Seino Y, Fukumoto H, Koh G, Yano H, Inagaki N, Yamada Y, Inoue K, Manabe T, Imura H. Over-expression of facilitative glucose transporter genes in human cancer. Biochem Biophys Res Commun 1990; 170:223–230.PubMed Yamamoto T, Seino Y, Fukumoto H, Koh G, Yano H, Inagaki N, Yamada Y, Inoue K, Manabe T, Imura H. Over-expression of facilitative glucose transporter genes in human cancer. Biochem Biophys Res Commun 1990; 170:223–230.PubMed
8.
go back to reference Lindholm P, Minn H, Leskinen-Kallio S, Bergman J, Ruotsalainen U, Joensuu H. Influence of the blood glucose concentration on FDG uptake in cancer—a PET study. J Nucl Med 1993; 34:1–6.PubMed Lindholm P, Minn H, Leskinen-Kallio S, Bergman J, Ruotsalainen U, Joensuu H. Influence of the blood glucose concentration on FDG uptake in cancer—a PET study. J Nucl Med 1993; 34:1–6.PubMed
9.
go back to reference Brown RS, Leung JY, Fisher SJ, Frey KA, Ethier SP, Wahl RL. Intratumoral distribution of tritiated-FDG in breast carcinoma: correlation between Glut-1 expression and FDG uptake. J Nucl Med 1996; 37:1042–1047.PubMed Brown RS, Leung JY, Fisher SJ, Frey KA, Ethier SP, Wahl RL. Intratumoral distribution of tritiated-FDG in breast carcinoma: correlation between Glut-1 expression and FDG uptake. J Nucl Med 1996; 37:1042–1047.PubMed
10.
go back to reference Higashi T, Saga T, Nakamoto Y, Ishimori T, Mamede MH, Wada M, Doi R, Hosotani R, Imamura M, Konishi J. Relationship between retention index in dual-phase (18)F-FDG PET, and hexokinase-II and glucose transporter-1 expression in pancreatic cancer. J Nucl Med 2002; 43:173–180.PubMed Higashi T, Saga T, Nakamoto Y, Ishimori T, Mamede MH, Wada M, Doi R, Hosotani R, Imamura M, Konishi J. Relationship between retention index in dual-phase (18)F-FDG PET, and hexokinase-II and glucose transporter-1 expression in pancreatic cancer. J Nucl Med 2002; 43:173–180.PubMed
11.
go back to reference Brown RS, Goodman TM, Zasadny KR, Greenson JK, Wahl RL. Expression of hexokinase II and Glut-1 in untreated human breast cancer. Nucl Med Biol 2002; 29:443–453.CrossRefPubMed Brown RS, Goodman TM, Zasadny KR, Greenson JK, Wahl RL. Expression of hexokinase II and Glut-1 in untreated human breast cancer. Nucl Med Biol 2002; 29:443–453.CrossRefPubMed
12.
go back to reference Mellanen P, Minn H, Grenman R, Harkonen P. Expression of glucose transporters in head-and-neck tumors. Int J Cancer 1994; 56:622–629.PubMed Mellanen P, Minn H, Grenman R, Harkonen P. Expression of glucose transporters in head-and-neck tumors. Int J Cancer 1994; 56:622–629.PubMed
13.
go back to reference Marom EM, Aloia TA, Moore MB, Hara M, Herndon JE 2nd, Harpole DH Jr, Goodman PC, Patz EF Jr. Correlation of FDG-PET imaging with Glut-1 and Glut-3 expression in early-stage non-small cell lung cancer. Lung Cancer 2001; 33:99–107.PubMed Marom EM, Aloia TA, Moore MB, Hara M, Herndon JE 2nd, Harpole DH Jr, Goodman PC, Patz EF Jr. Correlation of FDG-PET imaging with Glut-1 and Glut-3 expression in early-stage non-small cell lung cancer. Lung Cancer 2001; 33:99–107.PubMed
14.
go back to reference Higashi T, Tamaki N, Honda T, Torizuka T, Kimura T, Inokuma T, Ohshio G, Hosotani R, Imamura M, Konishi J. Expression of glucose transporters in human pancreatic tumors compared with increased FDG accumulation in PET study. J Nucl Med 1997; 38:1337–1344.PubMed Higashi T, Tamaki N, Honda T, Torizuka T, Kimura T, Inokuma T, Ohshio G, Hosotani R, Imamura M, Konishi J. Expression of glucose transporters in human pancreatic tumors compared with increased FDG accumulation in PET study. J Nucl Med 1997; 38:1337–1344.PubMed
15.
go back to reference UICC: TNM classification of malignant tumors, 4th edn. In: Hermanek P, Sobin LH, eds. Berlin Heidelberg New York: Springer, 1987. UICC: TNM classification of malignant tumors, 4th edn. In: Hermanek P, Sobin LH, eds. Berlin Heidelberg New York: Springer, 1987.
16.
go back to reference Hamacher K, Coenen HH, Stocklin G. Efficient stereospecific synthesis of no-carrier-added 2-[18F]-fluoro-2-deoxy-d-glucose using aminopolyether supported nucleophilic substitution. J Nucl Med 1986; 27:235–238.PubMed Hamacher K, Coenen HH, Stocklin G. Efficient stereospecific synthesis of no-carrier-added 2-[18F]-fluoro-2-deoxy-d-glucose using aminopolyether supported nucleophilic substitution. J Nucl Med 1986; 27:235–238.PubMed
17.
go back to reference Zhang H, Inoue T, Alyafei S, Tian M, Oriuchi N, Endo K. Tumour detectability in 2-dimensional and 3-dimensional positron emission tomography using the SET-2400 W: a phantom study. Nucl Med Commun 2001; 22:305–314.CrossRefPubMed Zhang H, Inoue T, Alyafei S, Tian M, Oriuchi N, Endo K. Tumour detectability in 2-dimensional and 3-dimensional positron emission tomography using the SET-2400 W: a phantom study. Nucl Med Commun 2001; 22:305–314.CrossRefPubMed
18.
go back to reference Younes M, Lechago LV, Somoano JR, Mosharaf M, Lechago J. Wide expression of the human erythrocyte glucose transporter Glut1 in human cancers. Cancer Res 1996; 56:1164–1167.PubMed Younes M, Lechago LV, Somoano JR, Mosharaf M, Lechago J. Wide expression of the human erythrocyte glucose transporter Glut1 in human cancers. Cancer Res 1996; 56:1164–1167.PubMed
19.
go back to reference Younes M, Lechago LV, Somoano JR, Mosharaf M, Lechago J. Immunohistochemical detection of Glut3 in human tumors and normal tissues. Anticancer Res 1997; 17:2747–2750.PubMed Younes M, Lechago LV, Somoano JR, Mosharaf M, Lechago J. Immunohistochemical detection of Glut3 in human tumors and normal tissues. Anticancer Res 1997; 17:2747–2750.PubMed
20.
go back to reference Younes M, Brown RW, Stephenson M, Gondo M, Cagle PT. Overexpression of Glut1 and Glut3 in stage I nonsmall cell lung carcinoma is associated with poor survival. Cancer 1997; 80:1046–1051.CrossRefPubMed Younes M, Brown RW, Stephenson M, Gondo M, Cagle PT. Overexpression of Glut1 and Glut3 in stage I nonsmall cell lung carcinoma is associated with poor survival. Cancer 1997; 80:1046–1051.CrossRefPubMed
21.
go back to reference Bos R, van Der Hoeven JJ, van Der Wall E, van Der Groep P, van Diest PJ, Comans EF, Joshi U, Semenza GL, Hoekstra OS, Lammertsma AA, Molthoff CF. Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol 2002; 20:379–387.PubMed Bos R, van Der Hoeven JJ, van Der Wall E, van Der Groep P, van Diest PJ, Comans EF, Joshi U, Semenza GL, Hoekstra OS, Lammertsma AA, Molthoff CF. Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol 2002; 20:379–387.PubMed
22.
go back to reference Aoki D, Kawakami H, Nozawa S, Udagawa Y, Iizuka R, Hirano H. Differences in lectin binding patterns of normal human endometrium between proliferative and secretory phases. Histochemistry 1989; 92:177–184.PubMed Aoki D, Kawakami H, Nozawa S, Udagawa Y, Iizuka R, Hirano H. Differences in lectin binding patterns of normal human endometrium between proliferative and secretory phases. Histochemistry 1989; 92:177–184.PubMed
23.
go back to reference Mueckler M, Caruso C, Baldwin SA, et al. Sequence and structure of a human glucose transporter. Science 1985; 229:941–945.PubMed Mueckler M, Caruso C, Baldwin SA, et al. Sequence and structure of a human glucose transporter. Science 1985; 229:941–945.PubMed
24.
go back to reference White MK, Bramwell ME, Harris H. Kinetic parameters of hexose transport in hybrids between malignant and nonmalignant cells. J Cell Sci 1983; 62:49–80.PubMed White MK, Bramwell ME, Harris H. Kinetic parameters of hexose transport in hybrids between malignant and nonmalignant cells. J Cell Sci 1983; 62:49–80.PubMed
25.
go back to reference Lindholm P, Minn H, Leskinen-Kallio S, Bergman J, Ruotsalainen U, Joensuu H. Influence of the blood glucose concentration on FDG uptake in cancer—a PET study. J Nucl Med 1993; 34:1–6.PubMed Lindholm P, Minn H, Leskinen-Kallio S, Bergman J, Ruotsalainen U, Joensuu H. Influence of the blood glucose concentration on FDG uptake in cancer—a PET study. J Nucl Med 1993; 34:1–6.PubMed
26.
go back to reference Kallinowski F, Schlenger KH, Runkel S, Kloes M, Stohrer M, Okunieff P, Vaupel P. Blood flow, metabolism, cellular microenvironment, and growth rate of human tumor xenografts. Cancer Res 1989; 49:3759–3764.PubMed Kallinowski F, Schlenger KH, Runkel S, Kloes M, Stohrer M, Okunieff P, Vaupel P. Blood flow, metabolism, cellular microenvironment, and growth rate of human tumor xenografts. Cancer Res 1989; 49:3759–3764.PubMed
27.
go back to reference Heber D, Byerley LO, Tchekmedyian NS. Hormonal and metabolic abnormalities in the malnourished cancer patient: effects on host-tumor interaction. JPEN J Parenter Enteral Nutr 1992; 16 (6 Suppl):60S–64S. Heber D, Byerley LO, Tchekmedyian NS. Hormonal and metabolic abnormalities in the malnourished cancer patient: effects on host-tumor interaction. JPEN J Parenter Enteral Nutr 1992; 16 (6 Suppl):60S–64S.
28.
go back to reference Musholt TJ, Musholt PB, Dehdashti F, Moley JF. Evaluation of fluorodeoxyglucose-positron emission tomographic scanning and its association with glucose transporter expression in medullary thyroid carcinoma and pheochromocytoma: a clinical and molecular study. Surgery 1997; 122:1049–1060.PubMed Musholt TJ, Musholt PB, Dehdashti F, Moley JF. Evaluation of fluorodeoxyglucose-positron emission tomographic scanning and its association with glucose transporter expression in medullary thyroid carcinoma and pheochromocytoma: a clinical and molecular study. Surgery 1997; 122:1049–1060.PubMed
29.
go back to reference Kunkel M, Reichert TE, Benz P, Lehr HA, Jeong JH, Wieand S, Bartenstein P, Wagner W, Whiteside TL. Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma. Cancer 2003; 97:1015–1024.CrossRefPubMed Kunkel M, Reichert TE, Benz P, Lehr HA, Jeong JH, Wieand S, Bartenstein P, Wagner W, Whiteside TL. Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma. Cancer 2003; 97:1015–1024.CrossRefPubMed
30.
go back to reference Ito T, Noguchi Y, Satoh S, Hayashi H, Inayama Y, Kitamura H. Expression of facilitative glucose transporter isoforms in lung carcinomas: its relation to histologic type, differentiation grade, and tumor stage. Mod Pathol 1998; 11:437–443.PubMed Ito T, Noguchi Y, Satoh S, Hayashi H, Inayama Y, Kitamura H. Expression of facilitative glucose transporter isoforms in lung carcinomas: its relation to histologic type, differentiation grade, and tumor stage. Mod Pathol 1998; 11:437–443.PubMed
31.
go back to reference Reisser C, Eichhorn K, Herold-Mende C, Born AI, Bannasch P. Expression of facilitative glucose transport proteins during development of squamous cell carcinomas of the head and neck. Int J Cancer 1999; 80:194–198.CrossRefPubMed Reisser C, Eichhorn K, Herold-Mende C, Born AI, Bannasch P. Expression of facilitative glucose transport proteins during development of squamous cell carcinomas of the head and neck. Int J Cancer 1999; 80:194–198.CrossRefPubMed
32.
go back to reference Younes M, Lechago LV, Lechago J. Overexpression of the human erythrocyte glucose transporter occurs as a late event in human colorectal carcinogenesis and is associated with an increased incidence of lymph node metastases. Clin Cancer Res 1996; 2:1151–1154.PubMed Younes M, Lechago LV, Lechago J. Overexpression of the human erythrocyte glucose transporter occurs as a late event in human colorectal carcinogenesis and is associated with an increased incidence of lymph node metastases. Clin Cancer Res 1996; 2:1151–1154.PubMed
33.
go back to reference Mochizuki T, Tsukamoto E, Kuge Y, Kanegae K, Zhao S, Hikosaka K, Hosokawa M, Kohanawa M, Tamaki N. FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models. J Nucl Med 2001; 42:1551–1555.PubMed Mochizuki T, Tsukamoto E, Kuge Y, Kanegae K, Zhao S, Hikosaka K, Hosokawa M, Kohanawa M, Tamaki N. FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models. J Nucl Med 2001; 42:1551–1555.PubMed
34.
go back to reference Grobholz R, Hacker HJ, Thorens B, Bannasch P. Reduction in the expression of glucose transporter protein GLUT 2 in preneoplastic and neoplastic hepatic lesions and reexpression of GLUT 1 in late stages of hepatocarcinogenesis. Cancer Res 1993; 53:4204–4211.PubMed Grobholz R, Hacker HJ, Thorens B, Bannasch P. Reduction in the expression of glucose transporter protein GLUT 2 in preneoplastic and neoplastic hepatic lesions and reexpression of GLUT 1 in late stages of hepatocarcinogenesis. Cancer Res 1993; 53:4204–4211.PubMed
35.
go back to reference Tai PK, Liao JF, Hossler PA, Castor CW, Carter-Su C. Regulation of glucose transporters by connective tissue activating peptide-III isoforms. J Biol Chem 1992; 267:19579–19586.PubMed Tai PK, Liao JF, Hossler PA, Castor CW, Carter-Su C. Regulation of glucose transporters by connective tissue activating peptide-III isoforms. J Biol Chem 1992; 267:19579–19586.PubMed
36.
go back to reference Wagstaff P, Kang HY, Mylott D, Robbins PJ, White MK. Characterization of the avian GLUT1 glucose transporter: differential regulation of GLUT1 and GLUT3 in chicken embryo fibroblasts. Mol Biol Cell 1995; 6:1575–1589.PubMed Wagstaff P, Kang HY, Mylott D, Robbins PJ, White MK. Characterization of the avian GLUT1 glucose transporter: differential regulation of GLUT1 and GLUT3 in chicken embryo fibroblasts. Mol Biol Cell 1995; 6:1575–1589.PubMed
37.
go back to reference Minn H, Lapela M, Klemi PJ, Grenman R, Leskinen S, Lindholm P, Bergman J, Eronen E, Haaparanta M, Joensuu H. Prediction of survival with fluorine-18-fluoro-deoxyglucose and PET in head and neck cancer. J Nucl Med 1997; 38:1907–1911.PubMed Minn H, Lapela M, Klemi PJ, Grenman R, Leskinen S, Lindholm P, Bergman J, Eronen E, Haaparanta M, Joensuu H. Prediction of survival with fluorine-18-fluoro-deoxyglucose and PET in head and neck cancer. J Nucl Med 1997; 38:1907–1911.PubMed
38.
go back to reference Rege S, Safa AA, Chaiken L, Hoh C, Juillard G, Withers HR. Positron emission tomography: an independent indicator of radiocurability in head and neck carcinomas. Am J Clin Oncol 2000; 23:164–169.PubMed Rege S, Safa AA, Chaiken L, Hoh C, Juillard G, Withers HR. Positron emission tomography: an independent indicator of radiocurability in head and neck carcinomas. Am J Clin Oncol 2000; 23:164–169.PubMed
39.
go back to reference Baer S, Casaubon L, Schwartz MR, Marcogliese A, Younes M. Glut3 expression in biopsy specimens of laryngeal carcinoma is associated with poor survival. Laryngoscope 2002; 112:393–396.PubMed Baer S, Casaubon L, Schwartz MR, Marcogliese A, Younes M. Glut3 expression in biopsy specimens of laryngeal carcinoma is associated with poor survival. Laryngoscope 2002; 112:393–396.PubMed
Metadata
Title
Expression of Glut-1 and Glut-3 in untreated oral squamous cell carcinoma compared with FDG accumulation in a PET study
Authors
Mei Tian
Hong Zhang
Yoshiki Nakasone
Kenji Mogi
Keigo Endo
Publication date
01-01-2004
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 1/2004
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-003-1316-9

Other articles of this Issue 1/2004

European Journal of Nuclear Medicine and Molecular Imaging 1/2004 Go to the issue