Journal of Neuro-Oncology

, Volume 84, Issue 2, pp 141–145 | Cite as

Angiogenesis in primary central nervous system lymphoma (PCNSL)

  • Hiroaki TakeuchiEmail author
  • Ken Matsuda
  • Ryuhei Kitai
  • Kazufumi Sato
  • Toshihiko Kubota
Lab investigation-human/animal tissue


Angiogenesis and angiogenic growth factors have a major role in the pathogenesis of malignancies. However, very little is known about the clinical and histopathological relevance of angiogenesis in primary central nervous system lymphoma (PCNSL). We investigated that expression of vascular endothelial growth factor (VEGF) of the lymphoma cells and microvessel density (MVD) were examined in 19 patients with PCNSL. Additionally, the presence of the blood–brain barrier (BBB) was examined using immunohistochemistry and the electron microscopy. MVD was significantly higher in nine cases with VEGF immunoreactivity (VEGF+) than in ten cases with negative immunoreactivity for VEGF (VEGF−) (< 0.001). VEGF expression was significantly associated with a longer survival (P < 0.005). BBB markers were negative in angiogenic vessels of VEGF+. BBB markers were identified in vessels surrounding tumor cells and tight junctions were also preserved in the capillary endothelium surrounding tumor cells in VEGF−. Angiogenesis is associated with VEGF expression and an absent BBB in the vessels of PCNSL. The BBB may be preserved in lesions with lymphoma cell infiltration, especially in VEGF− PCNSL. VEGF may have a prognostic effect in PCNSL.


Primary central nervous system lymphoma Angiogenesis Blood–brain barrier VEGF 


  1. 1.
    Bairey O, Zimra Y, Kaganovsky E, Shaklai M, Okon E, Rabizadeh E (2000) Microvessel density in chemosensitive and chemoresistant diffuse large B-cell lymphomas. Med Oncol 17(4):314–318PubMedGoogle Scholar
  2. 2.
    Bertolini F, Paolucci M, Peccatori F, Cinieri S, Agazzi A, Ferrucci PF, Cocorocchio E, Goldhirsch A, Martinelli G (1999) Angiogenic growth factors and endostatin in non-Hodgkin’s lymphoma. Br J Haematol 106(2):504–509PubMedCrossRefGoogle Scholar
  3. 3.
    Bono P, Teerenhovi L, Joensuu H (2003) Elevated serum endostatin is associated with poor outcome in patients with non-Hodgkin lymphoma. Cancer 97(11):2767–2775PubMedCrossRefGoogle Scholar
  4. 4.
    Hazar B, Paydas S, Zorludemir S, Sahin B, Tuncer I (2003) Prognostic significance of microvessel density and vascular endothelial growth factor (VEGF) expression in non-Hodgkin’s lymphoma. Leuk Lymphoma 44(12):2089–2093PubMedCrossRefGoogle Scholar
  5. 5.
    Ho CL, Sheu LF, Li CY (2002) Immunohistochemical expression of basic fibroblast growth factor, vascular endothelial growth factor, and their receptors in stage IV non-Hodgkin lymphoma. Appl Immunohistochem Mol Morphol 10(4):316–321PubMedCrossRefGoogle Scholar
  6. 6.
    List AF (2001) Vascular endothelial growth factor signaling pathway as an emerging target in hematologic malignancies. Oncologist 6(3):24–31PubMedCrossRefGoogle Scholar
  7. 7.
    Paulus W (1999) Classification, pathogenesis and molecular pathology of primary CNS lymphomas. J Neurooncol 43:203–208PubMedCrossRefGoogle Scholar
  8. 8.
    Ranieri G, Patruno R, Lionetti A, Di Summa A, Mattioli E, Bufo P, Pellecchia A, Ribatti D, Zizzo N (2005) Endothelial area and microvascular density in a canine non-Hodgkin’s lymphoma: an interspecies model of tumor angiogenesis. Leuk Lymphoma 46(11):1639–1643 PubMedCrossRefGoogle Scholar
  9. 9.
    Ribatti D, Vacca A, Nico B, Fanelli M, Roncali L, Dammacco F (1996) Angiogenesis spectrum in the stroma of B-cell non-Hodgkin’s lymphomas. An immunohistochemical and ultrastructural study. Eur J Haematol 56(1):45–53PubMedCrossRefGoogle Scholar
  10. 10.
    Ridell B, Norrby K (2001) Intratumoral microvascular density in malignant lymphomas of B-cell origin. APMIS 109(1):66–72PubMedCrossRefGoogle Scholar
  11. 11.
    Rubenstein J, Fischbein N, Aldape K, Burton E, Shuman M (2002) Hemorrhage and VEGF expression in a case of primary CNS lymphoma. J Neurooncol 58(1):53–56PubMedCrossRefGoogle Scholar
  12. 12.
    Salven P, Teerenhovi L, Joensuu H (1997) A high pretreatment serum vascular endothelial growth factor concentration is associated with poor outcome in non-Hodgkin’s lymphoma. Blood 90(8):3167–3172PubMedGoogle Scholar
  13. 13.
    Schabet M (1999) Epidemiology of primary CNS lymphoma. J Neurooncol 43(3):199–201PubMedCrossRefGoogle Scholar
  14. 14.
    Vacca A, Ribatti D, Ruco L, Giacchetta F, Nico B, Quondamatteo F, Ria R, Iurlaro M, Dammacco F (1999) Angiogenesis extent and macrophage density increase simultaneously with pathological progression in B-cell non-Hodgkin’s lymphomas. Br J Cancer 79(5):965–970PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Hiroaki Takeuchi
    • 1
    Email author
  • Ken Matsuda
    • 1
  • Ryuhei Kitai
    • 1
  • Kazufumi Sato
    • 1
  • Toshihiko Kubota
    • 1
  1. 1.Department of Neurosurgery, Faculty of Medical SciencesUniversity of FukuiEiheijiJapan

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