Immunohistochemical Study of CD68 and CR3/43 in Astrocytic Gliomas
Keywords:CD68, Astrocytoma, CR3/43, Immunohistochemistry, Gliomas, Macrophages, MHC Class II, Microglia, Neoplasms
Diffuse and high-grade astrocytomas are invasive neoplasms which grow diffusely into the brain parenchyma. Microglia has been termed the brain's immune system, although its specific role remains uncertain. Objective of this study was to assess in a series of astrocytic neoplasms, the expression of a macrophage marker CD 68 and Major Histocompatibility Complex Class II CR3/43. We examined 10 pilocytic astrocytomas, 13 diffuse astrocytomas and 17 anaplastic astrocytomas. For macrophages we used the CD68 monoclonal mouse antibody. For assessing the presence of MHC Class II complexes we used the specific monoclonal antibody CR3/43. CD68-positive mononuclear cells were observed in perivascular and hypoxic areas, within neoplastic tissue, inside and contiguous to vessel wall. CR3/43 positive complexes were detected in mononuclear elongated elements with amoeboid extensions strictly attached to endothelial cells, or contiguous to perinecrotic areas within neoplastic tissue. We suggest an active involvement of macrophage/microglia infiltrates in neovascularization and malignancy in astrocytomas. Macrophage infiltration and major histocompatibility complex class II complexes reactivity in gliomas could also suggest the occurrence of immune surveillance with a preliminary host's immune response. In addition, macrophages could promote angiogenesis mechanisms and induction of tumor growth.
Mantovani A, Schioppa T, Porta C, Allavena P, Sica A. Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Rev 2006; 25: 315-22. http://dx.doi.org/10.1007/s10555-006-9001-7
Siveen KS, Kuttan, G. Role of macrophages in tumor progression. Immunol Lett 2009; 123: 97-102. http://dx.doi.org/10.1016/j.imlet.2009.02.011
Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 2004; 4: 71-8. http://dx.doi.org/10.1038/nrc1256
Roggendorf W, Strupp S, Paulus W. Distribution and characterization of microglia/macrophages in human brain tumors. Acta Neuropathol 1996; 92: 288-93. http://dx.doi.org/10.1007/s004010050520
Moore S, Thanos S. The concept of microglia in relation to central nervous system disease and regeneration. Prog Neurobiol 1996; 48: 461-70. http://dx.doi.org/10.1016/0301-0082(95)00051-8
Caffo M, Caruso G, Germanò A, Galatioto S, Meli F, Tomasello F. CD68 and CR3/43 immunohistochemical expression in secretory meningiomas. Neurosurgery 2005; 57: 551-7. http://dx.doi.org/10.1227/01.NEU.0000170440.32720.77
Badie B, Schartner J. Role of microglia in glioma biology. Microsc Res Techn 2001; 54: 106-13. http://dx.doi.org/10.1002/jemt.1125
Crowther M, Brown NJ, Bishop ET, Lewis CE. Microenvironmental influence on macrophage regulation of angiogenesis in wounds and malignant tumors. J Leukoc Biol 2001; 70: 478-90.
Shono T, Ono M, Izumi H, Jimi SI, Matsushima, K, Okamoto, T. Involvement of the transcription factor NFκB in tubular morphogenesis of human microvascular endothelial cells by oxidative stress. Mol Cell Biol 1996; 16: 4231-9.
Venza M, Visalli M, Alafaci C, et al. Interleukin-8 (IL-8) overexpression in astrocytomas is induced by prostaglandin E2 (PGE2)and is associated to the transcription factors CCAAT enhancer binding protein-beta (C/EPB-β) and C/EBP Homologous Protein (CHOP). Neurosurgery 2011; 69: 713-21. http://dx.doi.org/10.1227/NEU.0b013e31821954c6
Tran CT, Wolz P, Egensperger R, Kosel S, Imai Y, Bise K. Differential expression of MHC class II molecules by microglia and neoplastic astroglia: relevance for the escape of astrocytoma cells from immune surveillance. Neuropathol Appl Neurobiol 1998; 24: 293-301. http://dx.doi.org/10.1046/j.1365-2990.1998.00120.x
Nishie A, Ono M, Shono T, Fukushi J, Otsubo M, Onoue H. Macrophage infiltration and heme oxygenase-1 expression correlate with angiogenesis in human gliomas. Clin Canc Res 1999; 5: 1107-13.
Ahmed F, Wyckoff J, Lin EY, et al. GFP expression in the mammary gland for imaging of mammary tumor cells in transgenic mice. Cancer Res 2002; 62: 7166-9.
Strojnik T, Kavalar R, Zajc I, Diamandis EP, Oikonomopoulou K, Lah TT. Prognostic impact of CD68 and kallikrein 6 in human glioma. Anticancer Res 2009; 29: 3269-79.
Markovic DS, Glass R, Synowitz M, Rooijen N, Kettenmann H. Microglia stimulate the invasiveness of glioma cells by increasing the activity of metalloprotease-2. J Neuropathol Exp Neurol 2005; 64: 754-62. http://dx.doi.org/10.1097/01.jnen.0000178445.33972.a9
Caffo M, Germanò A, Caruso G, et al. An immunohistochemical study of extracellular matrix proteins laminin, fibronectin and type IV collagen in paediatric glioblastoma multiforme. Acta Neurochir 2004; 146: 1113-8. http://dx.doi.org/10.1007/s00701-004-0344-y
Tibbets KM, Emnett RJ, Gao F, Perry A, Gutmann DH, Leonard JR. Histopathological predictors of pilocytic astrocytoma event-free survival. Acta Neuropathol 2009; 117: 657-65. http://dx.doi.org/10.1007/s00401-009-0506-3
Streit WJ, Kincald-Colton CA. The brain’s immune system. Sci Am 1995; 273: 54-61. http://dx.doi.org/10.1038/scientificamerican1195-54
Graeber MB, Bise K, Mehraein P. CR3/43, a marker for activated human microglia: application to diagnostic neuropathology. Neuropathol Appl Neurobiol 1994; 20: 406-8. http://dx.doi.org/10.1111/j.1365-2990.1994.tb00987.x
Rossi ML, Cruz Sanchez F, Hughes JT, Esiri MM, Coakham HB. Immunocytochemical study of the cellular immune response in meningiomas. J Clin Pathol 1988; 41: 314-9. http://dx.doi.org/10.1136/jcp.41.3.314
Komohara Y, Ohnishi K, Kuratsu J, Takeya M. Possible involvement of the M2 anti-inflammatory macrophage phenotype in growth of human gliomas. J Pathol 2008; 216: 15-24. http://dx.doi.org/10.1002/path.2370