Clinical and Experimental Medicine

, Volume 9, Issue 2, pp 157–163 | Cite as

ICAM-1 (Lys469Glu) and PECAM-1 (Leu125Val) polymorphisms in diffuse astrocytomas

  • Regislaine Valéria Burim
  • Silvia Aparecida Teixeira
  • Benedicto Oscar Colli
  • Fernanda Maris Peria
  • Luis Fernando Tirapelli
  • Suely Kazue Nagahashi Marie
  • Suzana Maria Fleury Malheiros
  • Sueli Mieko Oba-Shinjo
  • Alberto Alain Gabbai
  • Paulo Andrade Lotufo
  • Carlos Gilberto Carlotti-Júnior
Original Article


Cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) play an important role in glioma invasion and angiogenesis. The aim of this study was to investigate whether specific genetic polymorphisms of ICAM-1 and PECAM-1 could be associated with glioma development and progression. Single-nucleotide polymorphism in codon 469 of ICAM-1 and codon 125 of PECAM-1 were examined in 158 patients with astrocytomas and 162 controls using polymerase chain reaction and restriction enzyme analysis. The distribution of PECAM-1 polymorphic genotypes in astrocytomas did not show any significant difference. However, a specific ICAM-1 genotype (G/G, corresponding to Lys469Glu) exhibited higher frequency in grade II astrocytomas compared to controls, grade III, and grade IV astrocytomas; suggesting that this polymorphism could be involved in the development of grade II astrocytomas.


Astrocytoma Polymorphism PECAM-1 ICAM-1 



The authors are grateful to Dr. Mariano S. Viapiano for comments on an earlier manuscript and to Amelia G. de Araújo and Julia M.Y. Komoto for technical assistance. This study was supported by grants from FAPESP, FAEPA,CAPES, LICR.

Conflict of interest statement

The authors declare that they have no conflict of interest related to the publication of this manuscript.


  1. 1.
    Kleihues P, Burger PC, Collins VP, Newcomb EW, Ohgaki H, Cavenee WK (2000) Pathology and genetics of tumours of the central nervous system. In: Kleihues P, Cavenee WK (eds) World Health Organization Classification of Tumours. IARC Press, Lyon, pp 6–69Google Scholar
  2. 2.
    Shapiro JR (2002) Genetic alterations associated with adult diffuse astrocytic tumors. Am J Med Genet 115(3):194–201PubMedCrossRefGoogle Scholar
  3. 3.
    Compostella A, Tosoni A, Blatt V, Franceschi E, Brandes AA (2007) Prognostic factors for anaplastic astrocytomas. J Neurooncol 81(3):295–303PubMedCrossRefGoogle Scholar
  4. 4.
    Cavenee WK (2000) High-grade gliomas with chromosome 1p loss. J Neurosurg 92(6):1080–1081PubMedGoogle Scholar
  5. 5.
    Preusser M, Haberler C, Hainfellner JA (2006) Malignant glioma: neuropathology and neurobiology. Wien Med Wochenschr 156(11–12):332–337PubMedCrossRefGoogle Scholar
  6. 6.
    Ohgaki H, Kleihues P (2007) Genetic pathways to primary and secondary glioblastoma. Am J Pathol 170(5):1445–1453PubMedCrossRefGoogle Scholar
  7. 7.
    Gudinaviciene I, Pranys D, Juozaityte E (2004) Impact of morphology and biology on the prognosis of patients with gliomas. Medicina (Kaunas) 40(2):112–120Google Scholar
  8. 8.
    Daumas-Duport C, Varlet P, Tucker ML, Beuvon F, Cervera P, Chodkiewicz JP (1997) Oligodendrogliomas. Part I: patterns of growth, histological diagnosis, clinical and imaging correlations: a study of 153 cases. J Neurooncol 34(1):37–59PubMedCrossRefGoogle Scholar
  9. 9.
    Aroca F, Renaud W, Bartoli C, Bouvier-Labit C, Figarella-Branger D (1999) Expression of PECAM-1/CD31 isoforms in human brain gliomas. J Neurooncol 43(1):19–25PubMedCrossRefGoogle Scholar
  10. 10.
    Kargiots O, Rao JS, Kryritsis AP (2006) Mechanisms of angiogenesis in gliomas. J Neurooncol 78:281–293CrossRefGoogle Scholar
  11. 11.
    Cavallo F, Martin-Fontecha A, Bellone M, Heltai S, Gatti E, Tornaghi P, Freschi M, Forni G, Dellabona P, Casorati G (1995) Co-expression of B7–1 and ICAM-1 on tumors is required for rejection and the establishment of a memory response. Eur J Immunol 25(5):1154–1162PubMedCrossRefGoogle Scholar
  12. 12.
    Nishio M, Spielman J, Lee RK, Nelson DL, Podack ER (1996) CD80 (B7.1) and CD54 (intracellular adhesion molecule-1) induce target cell susceptibility to promiscuous cytotoxic T cell lysis. J Immunol 157(10):4347–4353PubMedGoogle Scholar
  13. 13.
    Uzendoski K, Kantor JA, Abrams SI, Schlom J, Hodge JW (1997) Construction and characterization of a recombinant vaccinia virus expressing murine intercellular adhesion molecule-1: induction and potentiation of antitumor responses. Hum Gene Ther 8(7):851–860PubMedCrossRefGoogle Scholar
  14. 14.
    Salmaggi A, Eoli M, Frigerio S, Ciusani E, Silvani A, Boiardi A (1999) Circulating intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and plasma thrombomodulin levels in glioblastoma patients. Cancer Lett 146(2):169–172PubMedCrossRefGoogle Scholar
  15. 15.
    Demuth T, Berens ME (2004) Molecular mechanisms of glioma cell migration and invasion. J Neuro Oncol 70:217–228CrossRefGoogle Scholar
  16. 16.
    Vitolo D, Paradiso P, Uccini S, Ruco LP, Baroni CD (1996) Expression of adhesion molecules and extracellular matrix proteins in glioblastomas: relation to angiogenesis and spread. Histopathology 28:521–528PubMedCrossRefGoogle Scholar
  17. 17.
    Diamond MS, Staunton DE, Marlin SD, Springer TA (1991) Binding of the integrin Mac-1 (CD11b/CD18) to the third immunoglobulin-like domain of ICAM-1 (CD54) and its regulation by glycosylation. Cell 65:961–971PubMedCrossRefGoogle Scholar
  18. 18.
    Kuppner MC, van Meir E, Hamou MF, de Tribolet N (1990) Cytokine regulation of intercellular adhesion molecule-1 (ICAM-1) expression on human glioblastoma cells. Clin Exp Immunol 81(1):142–148PubMedGoogle Scholar
  19. 19.
    Yamanaka R, Tanaka R, Saito T (1994) Immunohistochemical analysis of tumor-infiltrating lymphocytes and adhesion molecules (ICAM-1, NCAM) in human gliomas. Neurol Med Chir (Tokyo) 34(9):583–587CrossRefGoogle Scholar
  20. 20.
    Meager A, Bird C, Mire-Sluis A (1996) Assays for measuring soluble cellular adhesion molecules and soluble cytokine receptors. J Immunol Methods 191(2):97–112PubMedCrossRefGoogle Scholar
  21. 21.
    Rice GE, Bevilacqua MP (1989) An inducible endothelial cell surface glycoprotein mediates melanoma adhesion. Science 246:1303–1306PubMedCrossRefGoogle Scholar
  22. 22.
    Goldberger A, Middleton KA, Oliver JA, Paddock C, Yan HC, DeLisser HM, Albelda SM, Newman PJ (1994) Biosynthesis and processing of the cell adhesion molecule PECAM-1 includes production of a soluble form. J Biol Chem 269(25):17183–17191PubMedGoogle Scholar
  23. 23.
    Newman PJ (1997) The biology of PECAM-1. J Clin Invest 99(1):3–8PubMedCrossRefGoogle Scholar
  24. 24.
    Albelda SM, Oliver PD, Romer LH, Buck CA (1990) EndoCAM: a novel endothelial cell–cell adhesion molecule. J Cell Biol 110(4):1227–1237PubMedCrossRefGoogle Scholar
  25. 25.
    Matsumura T, Wolff K, Petzelbauer P (1997) Endothelial cell tube formation depends on cadherin 5 and CD31 interactions with filamentous actin. J Immunol 158(7):3408–3416PubMedGoogle Scholar
  26. 26.
    DeLisser HM, Christofidou-Solomidou M, Strieter RM, Burdick MD, Robinson CS, Wexler RS, Kerr JS, Garlanda C, Merwin JR, Madri JA, Albelda SM (1997) Involvement of endothelial PECAM-1/CD31 in angiogenesis. Am J Pathol 151(3):671–677PubMedGoogle Scholar
  27. 27.
    Kim CS, Wang T, Madri JA (1998) Platelet endothelial cell adhesion molecule-1 expression modulates endothelial cell migration in vitro. Lab Invest 78(5):583–590PubMedGoogle Scholar
  28. 28.
    Listi F, Candore G, Lio D, Cavallone L, Colonna-Romano G, Caruso M, Hoffmann E, Caruso C (2004) Association between platelet endothelial cellular adhesion molecule 1 (PECAM-1/CD31) polymorphisms and acute myocardial infarction: a study in patients from Sicily. Eur J Immunogenet 31(4):175–178PubMedCrossRefGoogle Scholar
  29. 29.
    Matsuzawa J, Sugimura K, Matsuda Y et al (2003) Association between K469E allele of intercellular adhesion molecule 1 gene and inflammatory bowel disease in a Japanese population. Gut 52:75–78PubMedCrossRefGoogle Scholar
  30. 30.
    Vora DK, Rosenbloom CL, Beaudet AL, Cottingham RW (1994) Polymorphisms and linkage analysis for ICAM-1 and the selectin gene cluster. Genomics 21:473–477PubMedCrossRefGoogle Scholar
  31. 31.
    Iwao M, Morisaki H, Morisaki T (2004) Single-nucleotide polymorphism g. 1548G > A (E469 K) in human ICAM-1 gene affects mRNA splicing pattern and TPA-induced apoptosis. Biochem Biophys Res Commun 317(3):729–735PubMedCrossRefGoogle Scholar
  32. 32.
    Verity DH, Vaughan RW, Kondeatis E, Madanat W, Zureikat H, Fayyad F, Marr JE, Kanawati CA, Wallace GR, Stanford MR (2000) Intercellular adhesion molecule-1 gene polymorphisms in Behcet’s disease. Eur J Immunogenet 27(2):73–76PubMedCrossRefGoogle Scholar
  33. 33.
    Nejentsev S, Guja C, McCormack R, Cooper J, Howson JM, Nutland S, Rance H, Walker N, Undlien D, Ronningen KS, Tuomilehto-Wolf E, Tuomilehto J, Ionescu-Tirgoviste C, Gale EA, Bingley PJ, Gillespie KM, Savage DA, Carson DJ, Patterson CC, Maxwell AP, Todd JA (2003) Association of intercellular adhesion molecule-1 gene with type 1 diabetes. Lancet 362:1723–1724PubMedCrossRefGoogle Scholar
  34. 34.
    Kretowski A, Wawrusiewicz N, Mironczuk K, Mysliwiec J, Kretowska M, Kinalska I (2003) Intercellular adhesion molecule 1 gene polymorphisms in Graves’ disease. J Clin Endocrinol Metab 88(10):4945–4949PubMedCrossRefGoogle Scholar
  35. 35.
    Nejentsev S, Laaksonen M, Tienari PJ, Fernandez O, Cordell H, Ruutiainen J, Wikstrom J, Pastinen T, Kuokkanen S, Hillert J, Ilonen J (2003) Intercellular adhesion molecule-1 K469E polymorphism: study of association with multiple sclerosis. Hum Immunol 64(3):345–349PubMedCrossRefGoogle Scholar
  36. 36.
    Macchioni P, Boiardi L, Casali B, Nicoli D, Farnetti E, Salvarani C (2000) Intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms in Italian patients with rheumatoid arthritis. Clin Exp Rheumatol 18(5):553–558PubMedGoogle Scholar
  37. 37.
    Behar E, Chao NJ, Hiraki DD, Krishnaswamy S, Brown BW, Zehnder JL, Grumet FC (1996) Polymorphism of adhesion molecule CD31 and its role in acute graft-versus-host disease. N Engl J Med 334(5):286–291PubMedCrossRefGoogle Scholar
  38. 38.
    Serebruany VL, Murugesan SR, Pothula A, Semaan H, Gurbel PA (1999) Soluble PECAM-1, but not P-selectin, nor osteonectin identify acute myocardial infarction in patients presenting with chest pain. Cardiology 91(1):50–55PubMedCrossRefGoogle Scholar
  39. 39.
    Elrayess MA, Webb KE, Flavell DM, Syvanne M, Taskinen MR, Frick MH, Nieminen MS, Kesaniemi YA, Pasternack A, Jukema JW, Kastelein JJ, Zwinderman AH, Humphries SE (2003) A novel functional polymorphism in the PECAM-1 gene (53G > A) is associated with progression of atherosclerosis in the LOCAT and REGRESS studies. Atherosclerosis 168(1):131–138PubMedCrossRefGoogle Scholar
  40. 40.
    Andreotti F, Porto I, Crea F, Maseri A (2002) Inflammatory gene polymorphisms and ischaemia heart disease: review of population association studies. Heart 87(2):107–112PubMedCrossRefGoogle Scholar
  41. 41.
    Auer J, Weber T, Berent R, Lassnig E, Lamm G, Eber B (2003) Genetic polymorphisms in cytokine and adhesion molecule genes in coronary artery disease. Am J Pharmacogenomics 3(5):317–328PubMedCrossRefGoogle Scholar
  42. 42.
    Sciacca FL, Ferri C, D’Alfonso S, Bolognesi E, Martinelli Boneschi F, Cuzzilla B, Colombo B, Comi G, Canal N, Grimaldi LM (2000) Association study of a new polymorphism in the PECAM-1 gene in multiple sclerosis. J Neuroimmunol 104(2):174–178PubMedCrossRefGoogle Scholar
  43. 43.
    Al-Omaishi J, Bashir R, Gendelman HE (1999) The cellular immunology of multiple sclerosis. J Leukoc Biol 65(4):444–452PubMedGoogle Scholar
  44. 44.
    Nichols WC, Antin JH, Lunetta KL, Terry VH, Hertel CE, Wheatley MA, Arnold ND, Siemieniak DR, Boehnke M, Ginsburg D (1996) Polymorphism of adhesion molecule CD31 is not a significant risk factor for graft-versus-host disease. Blood 88(12):4429–4434PubMedGoogle Scholar
  45. 45.
    Wei H, Fang L, Chowdhury SH, Gong N, Xiong Z, Song J, Mak KH, Wu S, Koay E, Sethi S, Lim YL, Chatterjee S (2004) Platelet-endothelial cell adhesion molecule-1 gene polymorphism and its soluble level are associated with severe coronary artery stenosis in Chinese Singaporean. Clin Biochem 37(12):1091–1097PubMedCrossRefGoogle Scholar
  46. 46.
    Howell WM, Pead PJ, Shek FW, Rose-Zerilli MJ, Armstrong T, Johnson CD, Fine DR, Iredale JP, Bateman AC (2005) Influence of cytokine and ICAM-1 gene polymorphisms on susceptibility to chronic pancreatitis. J Clin Pathol 58(6):595–599PubMedCrossRefGoogle Scholar
  47. 47.
    Yang X, Cullen SN, Li JH, Chapman RW, Jewell DP (2004) Susceptibility to primary sclerosing cholangitis is associated with polymorphisms of intercellular adhesion molecule-1. J Hepatol 40(3):375–379PubMedCrossRefGoogle Scholar
  48. 48.
    Gbadegesin RA, Cotton SA, Watson CJ, Brenchley PE, Webb NJ (2006) Association between ICAM-1 Gly-Arg polymorphism and renal parenchymal scarring following childhood urinary tract infection. Int J Immunogenet 33(1):49–53PubMedCrossRefGoogle Scholar
  49. 49.
    Sobel RA, Mitchell ME, Fondren G (1990) Intercellular adhesion molecule-1 (ICAM-1) in cellular immune reactions in the human central nervous system. Am J Pathol 136:1309PubMedGoogle Scholar
  50. 50.
    Akiyama H, Kawamata T, Yamada T, Tooyama I, Ishii T, McGeer PL (1993) Expression of intercellular adhesion molecule (ICAM)-1 by a subset of astrocytes in Alzheimer disease and some other degenerative neurological disorders. Acta Neuropathol 85:628PubMedCrossRefGoogle Scholar
  51. 51.
    Verbeek MM, Otte-Höller I, Westphal JR, Wesseling P, Ruiter DJ, de Waal RM (1994) Accumulation of intercellular adhesion molecule-1 in senile plaques in brain tissue of patients with Alzheimer’s disease. Am J Pathol 144:104PubMedGoogle Scholar
  52. 52.
    Lee SJ, Drabik K, Van Wagoner NJ, Lee S, Choi C, Dong Y, Benveniste EN (2000) ICAM-1-induced expression of proinflammatory cytokines in astrocytes: involvement of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways. J Immunol 165(8):4658–4666PubMedGoogle Scholar
  53. 53.
    Yamashita M, Yoshida S, Kennedy S, Ohara N, Motoyama S, Maruo T (2005) Association study of endometriosis and intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms in a Japanese population. J Soc Gynecol Investig 12(4):267–271PubMedCrossRefGoogle Scholar
  54. 54.
    Vigano P, Infantino M, Lattuada D et al (2003) Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms in endometriosis. Mol Hum Reprod 9:47–52PubMedCrossRefGoogle Scholar
  55. 55.
    Braun C, Zahn R, Martin K, Albert E, Folwaczny C (2001) Polymorphisms of the ICAM-1 gene are associated with inflammatory bowel disease, regardless of the p-ANCA status. Clin Immunol 101:357–360PubMedCrossRefGoogle Scholar
  56. 56.
    Kim EH, Mok JW, Bang D, Lee ES, Lee S, Park K (2003) Intercellular adhesion molecule-1 polymorphisms in Korean patients with Behcet’s disease. J Korean Med Sci 18:415–418PubMedCrossRefGoogle Scholar
  57. 57.
    Amoli MM, Mattey DL, Calvino MC, Garcia-Porrua C, Thomson W, Hajeer AH, Ollier WE, Gonzalez-Gay MA (2001) Polymorphism at codon 469 of the intercellular adhesion molecule-1 locus is associated with protection against severe gastrointestinal complications in Henoch-Schonlein purpura. J Rheumatol 28(5):1014–1018PubMedGoogle Scholar
  58. 58.
    Sasaoka T, Kimura A, Hohta SA, Fukuda N, Kurosawa T, Izumi T (2001) Polymorphisms in the platelet-endothelial cell adhesion molecule-1 (PECAM-1) gene, Asn563Ser and Gly670Arg, associated with myocardial infarction (in Japanese). Ann N Y Acad Sci 947:259–269PubMedGoogle Scholar
  59. 59.
    Fang L, Wei H, Chowdhury SH, Gong N, Song J, Heng CK, Sethi S, Koh TH, Chatterjee S (2005) Association of Leu125Val polymorphism of platelet endothelial cell adhesion molecule-1 (PECAM-1) gene & soluble level of PECAM-1 with coronary artery disease in Asian Indians. Indian J Med Res 121(2):92–99PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Regislaine Valéria Burim
    • 1
    • 2
  • Silvia Aparecida Teixeira
    • 1
  • Benedicto Oscar Colli
    • 1
  • Fernanda Maris Peria
    • 3
  • Luis Fernando Tirapelli
    • 1
  • Suely Kazue Nagahashi Marie
    • 4
  • Suzana Maria Fleury Malheiros
    • 5
  • Sueli Mieko Oba-Shinjo
    • 6
  • Alberto Alain Gabbai
    • 5
  • Paulo Andrade Lotufo
    • 7
  • Carlos Gilberto Carlotti-Júnior
    • 1
  1. 1.Department of Surgery and Anatomy, Faculty of Medicine of Ribeirão PretoUniversity of São Paulo (USP)Ribeirão PretoBrazil
  2. 2.Department of Clinical, Toxicological and Bromatological Analysis, School of Pharmaceutical Sciences of Ribeirão Preto, FCFRPUniversity of São PauloRibeirão PretoBrazil
  3. 3.Department of Internal Medicine, Faculty of Medicine of Ribeirão PretoUniversity of São Paulo (USP)Ribeirão PretoBrazil
  4. 4.Department of Neurology, Faculty of MedicineUniversity of São Paulo (USP)São PauloBrazil
  5. 5.Department of Neurology, Faculty of MedicineFederal University of São Paulo (UNIFESP)São PauloBrazil
  6. 6.Department of Internal Medicine, Faculty of MedicineUniversity of São Paulo (USP)São PauloBrazil
  7. 7.São Paulo University HospitalUniversity of São Paulo (USP)São PauloBrazil

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