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Expression of glucose transporter 1 is associated with loss of heterozygosity of chromosome 1p in oligodendroglial tumors WHO grade II

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Abstract

Objective Oligodendroglial tumors with a loss of heterozygosity of 1p (LOH1p) appear to have a better prognosis than oligodendrogliomas without LOH. Previously, we reported glucose uptake in low-grade oligodendroglial tumors to be related to LOH 1p status. Here, we performed an immunohistochemical study of the common glucose transporters (GLUT) in relation to LOH1p. Material and methods We examined 17 oligodendrogliomas (O II, 11 with LOH1p), 16 oligoastrocytomas (OA II, 5 with LOH1p) and 7 astrocytomas (A II, none with LOH1p). Confocal microscopy was performed for p53, GLUT-1, −3 and −12. Immunoreaction was rated semiquantitatively by percentage of positive cells and staining intensity on immunohistological stainings. Results Confocal microscopy depicted immunoreaction for GLUT-1, −3 and −12 in the cytoplasm of the tumor cells. Oligodendrogliomas revealed a lower immunoreactivity for GLUT-1 than oligoastrocytomas and astrocytomas (P = 0.0263). No differences in immunoreactivity were found for GLUT-3 and GLUT-12. GLUT-1 expression in tumors with LOH 1p was significantly lower than in tumors with wild type 1p status (P = 0.0017). GLUT-3 and GLUT-12 immunoreactivity was not correlated with LOH 1p. Conclusion Expression of GLUT-1 is significantly reduced in low-grade oligodendroglial tumors harboring LOH 1p. Further studies should address the functional role of GLUT-1 in regard to chemosensitivity of oligodendrogliomas.

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References

  • Bell GI, Kayano T, Buse JB et al (1990) Molecular biology of mammalian glucose transporters. Diabetes Care 13(3):198–208. doi:10.2337/diacare.13.3.198

    Article  PubMed  CAS  Google Scholar 

  • Blum R, Jacob-Hirsch J, Amariglio N et al (2005) Ras inhibition in glioblastoma down-regulates hypoxia-inducible factor-1alpha, causing glycolysis shutdown and cell death. Cancer Res 65(3):999–1006

    PubMed  CAS  Google Scholar 

  • Boado RJ, Black KL, Pardridge WM (1994) Gene expression of GLUT-3 and GLUT-1 glucose transporters in human brain tumors. Brain Res 27(1):51–57. doi:10.1016/0169-328X(94)90183-X

    Article  CAS  Google Scholar 

  • Bubendorf L, Nocito A, Moch H et al (2001) Tissue microarray (TMA) technology: miniaturized pathology archives for high-throughput in situ studies. J Pathol 195(1):72–79. doi:10.1002/path.893

    Article  PubMed  CAS  Google Scholar 

  • Cairncross JG, Ueki K, Zlatescu MC et al (1998) Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90(19):1473–1479. doi:10.1093/jnci/90.19.1473

    Article  PubMed  CAS  Google Scholar 

  • Cantuaria G, Fagotti A, Ferrandina G et al (2001) GLUT-1 expression in ovarian carcinoma: association with survival and response to chemotherapy. Cancer 92(5):1144–1150. doi :10.1002/1097-0142(20010901)92:5<1144::AID-CNCR1432>3.0.CO;2-T

    Article  PubMed  CAS  Google Scholar 

  • Cao X, Fang L, Gibbs S et al (2007) Glucose uptake inhibitor sensitizes cancer cells to daunorubicin and overcomes drug resistance in hypoxia. Cancer Chemother Pharmacol 59(4):495–505. doi:10.1007/s00280-006-0291-9

    Article  PubMed  CAS  Google Scholar 

  • Chandler JD, Williams ED, Slavin JL et al (2003) Expression and localization of GLUT-1 and GLUT-12 in prostate carcinoma. Cancer 97(8):2035–2042. doi:10.1002/cncr.11293

    Article  PubMed  CAS  Google Scholar 

  • Cher LM, Murone C, Lawrentschuk N et al (2006) Correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in gliomas using 18F-fluoromisonidazole, 18F-FDG PET, and immunohistochemical studies. J Nucl Med 47(3):410–418

    PubMed  CAS  Google Scholar 

  • Cohen J (1960) A coefficient of agreement for nominal scales. Educ Psychol Meas 20:37. doi:10.1177/001316446002000104

    Article  Google Scholar 

  • Flier JS, Mueckler M, McCall AL et al (1987) Distribution of glucose transporter messenger RNA transcripts in tissues of rat and man. J Clin Invest 79(2):657–661. doi:10.1172/JCI112864

    Article  PubMed  CAS  Google Scholar 

  • Gerhart DZ, Broderius MA, Borson ND et al (1992) Neurons and microvessels express the brain glucose transporter protein GLUT-3. Proc Natl Acad Sci USA 89(2):733–737. doi:10.1073/pnas.89.2.733

    Article  PubMed  CAS  Google Scholar 

  • Gude NM, Stevenson JL, Rogers S et al (2003) GLUT-12 expression in human placenta in first trimester and term. Placenta 24(5):566–570. doi:10.1053/plac.2002.0925

    Article  PubMed  CAS  Google Scholar 

  • Gude NM, Stevenson JL, Murthi P et al (2005) Expression of GLUT-12 in the fetal membranes of the human placenta. Placenta 26(1):67–72. doi:10.1016/j.placenta.2004.04.006

    Article  PubMed  CAS  Google Scholar 

  • Guerin C, Laterra J, Hruban RH et al (1990) The glucose transporter and blood-brain barrier of human brain tumors. Ann Neurol 28(6):758–765. doi:10.1002/ana.410280606

    Article  PubMed  CAS  Google Scholar 

  • Hartmann C, Mueller W, Lass U et al (2005) Molecular genetic analysis of oligodendroglial tumors. J Neuropathol Exp Neurol 64(1):10–14

    PubMed  CAS  Google Scholar 

  • Kalaria RN, Gravina SA, Schmidley JW et al (1988) The glucose transporter of the human brain and blood-brain barrier. Ann Neurol 24(6):757–764. doi:10.1002/ana.410240610

    Article  PubMed  CAS  Google Scholar 

  • Kanner AA, Staugaitis SM, Castilla EA et al (2006) The impact of genotype on outcome in oligodendroglioma: validation of the loss of chromosome arm 1p as an important factor in clinical decision making. J Neurosurg 104(4):542–550. doi:10.3171/jns.2006.104.4.542

    Article  PubMed  Google Scholar 

  • Kasanicki MA, Jessen KR, Baldwin SA et al (1989) Immunocytochemical localization of the glucose-transport protein in mammalian brain capillaries. Histochem J 21(1):47–51. doi:10.1007/BF01002471

    Article  PubMed  CAS  Google Scholar 

  • Kononen J, Bubendorf L, Kallioniemi A et al (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4(7):844–847. doi:10.1038/nm0798-844

    Article  PubMed  CAS  Google Scholar 

  • Loda M, Xu X, Pession A et al (2000) Membranous expression of glucose transporter-1 protein (GLUT-1) in embryonal neoplasms of the central nervous system. Neuropathol Appl Neurobiol 26(1):91–97. doi:10.1046/j.1365-2990.2000.00225.x

    Article  PubMed  CAS  Google Scholar 

  • Maher F, Vannucci S, Takeda J et al (1992) Expression of mouse-GLUT-3 and human-GLUT-3 glucose transporter proteins in brain. Biochem Biophys Res Commun 182(2):703–711. doi:10.1016/0006-291X(92)91789-S

    Article  PubMed  CAS  Google Scholar 

  • Martell RL, Slapak CA, Levy SB (1997) Effect of glucose transport inhibitors on vincristine efflux in multidrug-resistant murine erythroleukaemia cells overexpressing the multidrug resistance-associated protein (MRP) and two glucose transport proteins, GLUT1 and GLUT3. Br J Cancer 75(2):161–168

    PubMed  CAS  Google Scholar 

  • Moch H, Kononen T, Kallioniemi OP et al (2001) Tissue microarrays: what will they bring to molecular and anatomic pathology? Adv Anat Pathol 8(1):14–20. doi:10.1097/00125480-200101000-00002

    Article  PubMed  CAS  Google Scholar 

  • Morgello S, Uson RR, Schwartz EJ et al (1995) The human blood-brain barrier glucose transporter (GLUT-1) is a glucose transporter of gray matter astrocytes. Glia 14(1):43–54. doi:10.1002/glia.440140107

    Article  PubMed  CAS  Google Scholar 

  • Nagamatsu S, Sawa H, Wakizaka A et al (1993) Expression of facilitative glucose transporter isoforms in human brain tumors. J Neurochem 61(6):2048–2053. doi:10.1111/j.1471-4159.1993.tb07441.x

    Article  PubMed  CAS  Google Scholar 

  • Nishioka T, Oda Y, Seino Y et al (1992) Distribution of the glucose transporters in human brain tumors. Cancer Res 52(14):3972–3979

    PubMed  CAS  Google Scholar 

  • Padma MV, Said S, Jacobs M et al (2003) Prediction of pathology and survival by FDG PET in gliomas. J Neurooncol 64(3):227–237. doi:10.1023/A:1025665820001

    Article  PubMed  CAS  Google Scholar 

  • Pardridge WM, Boado RJ, Farrell CR (1990) Brain-type glucose transporter (GLUT-1) is selectively localized to the blood-brain barrier: studies with quantitative western blotting and in situ hybridization. J Biol Chem 265(29):18035–18040

    PubMed  CAS  Google Scholar 

  • Rastogi S, Banerjee S, Chellappan S et al (2007) GLUT-1 antibodies induce growth arrest and apoptosis in human cancer cell lines. Cancer Lett 257(2):244–251. doi:10.1016/j.canlet.2007.07.021

    Article  PubMed  CAS  Google Scholar 

  • Reiner A, Spona J, Reiner G et al (1986) Estrogen receptor analysis on biopsies and fine-needle aspirates from human breast carcinoma: correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Am J Pathol 125(3):443–449

    PubMed  CAS  Google Scholar 

  • Remmele W, Hildebrand U, Hienz HA (1986) Comparative histological, histochemical, immunohistochemical and biochemical studies on oestrogen receptors, lectin receptors, and Barr bodies in human breast cancer. Virchows Arch A Pathol Anat Histopathol 409(2):127–147

    Article  PubMed  CAS  Google Scholar 

  • Rogers S, Macheda ML, Docherty SE et al (2002) Identification of a novel glucose transporter-like protein-GLUT-12. Am J Physiol 282(3):E733–E738

    CAS  Google Scholar 

  • Rogers S, Docherty SE, Slavin JL et al (2003) Differential expression of GLUT-12 in breast cancer and normal breast tissue. Cancer Lett 193(2):225–233. doi:10.1016/S0304-3835(03)00010-7

    Article  PubMed  CAS  Google Scholar 

  • Schwartzenberg-Bar-Yoseph F, Armoni M, Karnieli E (2004) The tumor suppressor p53 down-regulates glucose transporters GLUT-1 and GLUT-4 gene expression. Cancer Res 64(7):2627–2633. doi:10.1158/0008-5472.CAN-03-0846

    Article  PubMed  CAS  Google Scholar 

  • Sembritzki O, Hagel C, Lamszus K et al (2002) Cytoplasmic localization of wildtype p53 in glioblastomas correlates with expression of vimentin and glial fibrillary acidic protein. Neuro-oncol 4(3):171–178. doi:10.1215/15228517-4-3-171

    Article  PubMed  CAS  Google Scholar 

  • Shows TB, Eddy RL, Byers MG et al (1987) Polymorphic human glucose transporter gene (GLUT) is on chromosome 1p31.3–p35. Diabetes 36(4):546–549. doi:10.2337/diabetes.36.4.546

    Article  PubMed  CAS  Google Scholar 

  • Stockhammer F, Thomale UW, Plotkin M et al (2007) Association between fluorine-18-labeled fluorodeoxyglucose uptake and 1p and 19q loss of heterozygosity in World Health Organization Grade II gliomas. J Neurosurg 106(4):633–637. doi:10.3171/jns.2007.106.4.633

    Article  PubMed  CAS  Google Scholar 

  • Tabernero A, Medina JM, Giaume C (2006) Glucose metabolism and proliferation in glia: role of astrocytic gap junctions. J Neurochem 99(4):1049–1061. doi:10.1111/j.1471-4159.2006.04088.x

    Article  PubMed  CAS  Google Scholar 

  • Watanabe T, Nakamura M, Kros JM et al (2002) Phenotype versus genotype correlation in oligodendrogliomas and low-grade diffuse astrocytomas. Acta Neuropathol 103(3):267–275. doi:10.1007/s004010100464

    Article  PubMed  CAS  Google Scholar 

  • Wharton SB, Maltby E, Jellinek DA et al (2007) Subtypes of oligodendroglioma defined by 1p, 19q deletions, differ in the proportion of apoptotic cells but not in replication-licensed non-proliferating cells. Acta Neuropathol 113(2):119–127. doi:10.1007/s00401-006-0177-2

    Article  PubMed  CAS  Google Scholar 

  • Yu S, Ding WG (1998) The 45 kDa form of glucose transporter 1 (GLUT-1) is localized in oligodendrocyte and astrocyte but not in microglia in the rat brain. Brain Res 797(1):65–72. doi:10.1016/S0006-8993(98)00372-2

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Petra Matylewski and Kathrein Permien for technical assistance and Frank L. Heppner for kindly supplying tumor samples. We are grateful to Suzanne Rogers, who kindly provided GLUT-12 antibody.

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Authors and Affiliations

  1. Department of Neurosurgery, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Florian Stockhammer & Michael Synowitz

  2. Department of Neuropathology, Ruprecht-Karls-Universität Heidelberg, 69120, Heidelberg, Germany

    Andreas von Deimling

  3. Clinical Cooperation Unit Neuropathology, German Cancer Center, 69120, Heidelberg, Germany

    Andreas von Deimling

  4. Institute of Neuropathology, Charité – Universitätsmedizin Berlin, 13353, Berlin, Germany

    Cristiane Blechschmidt

  5. Institute of Neuropathology, University of Bonn-Medical Center, 53105, Bonn, Germany

    Frank K. H. van Landeghem

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  1. Florian Stockhammer
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Correspondence to Florian Stockhammer.

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Stockhammer, F., von Deimling, A., Synowitz, M. et al. Expression of glucose transporter 1 is associated with loss of heterozygosity of chromosome 1p in oligodendroglial tumors WHO grade II. J Mol Hist 39, 553–560 (2008). https://doi.org/10.1007/s10735-008-9191-0

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  • DOI: https://doi.org/10.1007/s10735-008-9191-0

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