Skip to main content

Advertisement

SpringerLink
Log in

Endoglin (CD 105) is expressed on endothelial cells in the primary central nervous system lymphomas and correlates with survival

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Endoglin (CD105) is predominantly expressed on the cellular lineages within the vascular system and it is overexpressed on proliferating endothelial cells that participate in neoangiogenesis, with a weak or negative expression in the vascular endothelium of normal tissues. To investigate the correlation between the CD105 expression and possible prognostic markers or progression in the primary central nervous system lymphomas (PCNSLs), the present study assessed 26 cases of PCNSL by immunostaining for CD105 and CD34. Intratumoral microvessel density (IMVD) was determined in the hotspots and interfaces at a magnification of x200. According to the mean value, the patients were classified into lower-IMVD and higher-IMVD groups. When CD34 was used as a marker of angiogenesis, the survival rates of these two groups demonstrated no significant difference. In contrast, when CD105 was used as a marker of angiogenesis, the survival rate of the lower-IMVD group was significantly higher than that for the higher-IMVD group (P < 0.01). In the group of CD34-immunostained vessels, no difference was observed in IMVD between the hotspots and interfaces (P = 0.31). In the group with CD105-immunostained vessels, a greater IMVD was observed in the hotspots than in the interfaces (P < 0.01). These results suggested that the growth of PCNSLs was dependent on angiogenesis, that IMVD as determined by anti-CD105 monoclonal antibody was a reliable prognostic marker in PCNSLs, and that PCNSLs may therefore not require sufficient neoangiogenesis at the start of PCNSLs, however, it may instead require a higher rate of neoangiogenesis as they infiltrate and destroy the brain parenchyma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Chang C-C, Kampalath B, Schultz C, Bunyi-Teopengco E, Logan B, Eshoa C, Dincer AP, Perkins SL (2003) Expression of p53, c-Myc, or Bcl-6 suggests a poor prognosis in primary central nervous system diffuse large B-cell lymphoma among immunocompetent individuals. Arch Pathol Lab Med 127:208–212

    PubMed  Google Scholar 

  2. Paulus W, Jellinger K, Morgello S, Deckert-Schluter M (2000) Malignant lymphomas. In: Kleihues P, Cavenee WK (eds) Pathology and genetics of tumours of the nervous system. International Agency for Research on Cancer Press, Lyon, pp 198–203

    Google Scholar 

  3. Sugita Y, Tokunaga O, Nakashima A, Shigemori M (2004) SHP-1 expression in primary central nervous system B-cell lymphomas in immunocompetent patients reflects maturation stage of normal B cell counterparts. Pathol Int 54:659–666

    Article  PubMed  CAS  Google Scholar 

  4. Arai M, Sasaki S, Saito N, Nakazato Y (2005) Immunohistochemical analysis of cleaved caspase-3 detects high level of apoptosis frequently in diffuse large B-cell lymphomas of the central nervous system. Pathol Int 55:122–129

    Article  PubMed  CAS  Google Scholar 

  5. Bellamy WT, Richter L, Frutiger Y, Grogan TM (1999) Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies. Cancer Res 59:728–733

    PubMed  CAS  Google Scholar 

  6. Bodey B, Bodey JR B, Siegel SE, Kaiser HE (1998) Upregulation of endoglin (CD105) expression during childhood brain tumor-related angiogenesis. Anti-angiogenic therapy. Anticancer Res 18:1485–1500

    PubMed  CAS  Google Scholar 

  7. Choi WWL, Lewis MM, Lawson D, Yin-Goen Q, Birdsong GG, Cotsonis GA, Cohen C, Young AN (2005) Angiogenic and lymphangiogenic microvessel density in breast carcinoma: correlation with clinicopathologic parameters and VEGF-family gene expression. Mod Pathol 18:143–152

    Article  PubMed  CAS  Google Scholar 

  8. Dales JP, Garcia S, Carpentier S, Andrac L, Ramuz O, Lavaut MN, Allasia C, Bonnier P, Charpin C (2004) Long-term prognostic significance of neoangiogenesis in breast carcinomas: comparison of Tie-2/Tek, CD105, and CD 31 immunocytochemical expression. Hum Pathol 35:176–183

    Article  PubMed  CAS  Google Scholar 

  9. Duarte IG, Bufkin BL, Pennington MF, Gall AA, Cohen C, Kosinski AS, Mansour KA, Miller JI (1998) Angiogenesis as a predictor of survival after surgical resection for stage I non-small-cell lung cancer. J Thorac Cardiovasc Surg 115:652–658

    Article  PubMed  CAS  Google Scholar 

  10. Giatromanolaki A, Koukourakis M, O’Byrne K, Fox S, Whitehouse R, Talbot DC, Harris AL, Gatter KC (1996) Prognostic value of angiogenesis in operable non-small cell lung cancer. J Pathol 179:80–88

    Article  PubMed  CAS  Google Scholar 

  11. Hedvat CV, Comenzo RL, Teruya-Feldstein J, Olshen AB, Ely SA, Osman K, Zhang Y, Kalakonda N, Nimer SD (2003) Insights into extramedullary tumour cell growth revealed by expression profiling of human plasmacytomas and multiple myeloma. Br J Hematol 122:728–744

    Article  CAS  Google Scholar 

  12. Houthoff HJ, Poppema S, Ebels EJ, Elema JD (1978) Intracranial malignant lymphomas. A morphologic and immunocytologic study of twenty cases. Acta Neuropathol (Ber) 44:203–210

    Article  CAS  Google Scholar 

  13. Minhajat R, Mori D, Yamasaki F, Sugita Y, Satoh T, Tokunaga O (2005) Endoglin (CD 105) expression in angiogenesis of colon cancer; analysis using tissue microarrays and comparison with other endothelial markers. Vichows Arch 22:1–8

    Google Scholar 

  14. Okada K, Satoh T, Fujimoto K, Tokunaga O (2004) Interaction between morphology and angiogenesis in human early colorectal cancers. Pathol Int 54:490–497

    Article  PubMed  Google Scholar 

  15. Rubenstein J, Fischbein N, Aldape K, Burton E, Shuman M (2002) Hemorrhage and VEGF expression in a case of primary CNS lymphoma. J Neuro-Oncol 58:53–56

    Article  Google Scholar 

  16. Saad RS, EL-Gohary Y, Memari E, Liu YL, Silverman JF (2005) Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in esophageal adenocarcinoma. Hum Pathol 36:955–961

    Article  PubMed  CAS  Google Scholar 

  17. Salven P, Orpana A, Teerenhovi L, Joensuu H (2000) Simultaneous elevation in the serum concentrations of the angiogenic growth factors VEGF and bFGF is an independent predictor of poor prognosis in non-Hodgkin lymphoma: a single-institution study of 200 patients. Blood 96:3712–3718

    PubMed  CAS  Google Scholar 

  18. Santos L, Costa C, Pereira S, Koch M, Amaro T, Cardoso F, Guimaraes T, Bento MJ, Lobo F, Pinto S, Lopes C (2003) Neovascularisation is a prognostic factor of early recurrence in T1/G2 urothelial bladder tumours. Ann Oncol 14:1419–1424

    Article  PubMed  CAS  Google Scholar 

  19. Takahashi N, Haba A, Matsuno F, Seon BK (2001) Antiangogenic therapy of established tumors in human skin/severe combined immunodeficiency mouse chimeras by anti-endoglin (CD105) monoclonal antibodies and synergy between anti-endoglin antibody and cyclophosphamide. Cancer Res 61:7846–7854

    PubMed  CAS  Google Scholar 

  20. Tanaka F, Otake Y, Yanagiha K, Kawano Y, Miyahara R, Li M, Ishikawa S, Wada H (2003) Correlation between apoptotic index and angiogenesis in non-small cell lung cancer: comparison between CD105 and CD34 as a marker of angiogenesis. Lung Cancer 39:289–296

    Article  PubMed  Google Scholar 

  21. Yamamoto S, Yasui W, Kitadai Y, Yokozaki H, Haruma K, Kajiyama G, Tahara E (1998) Expression of vascular endothelial growth factor in human gastric carcinomas. Pathol Int 48:499–506

    Article  PubMed  CAS  Google Scholar 

  22. Yao Y, Kubota T, Takeuchi H, Sato K (2005) Prognostic significance of microvessel density determined by an anti-CD105/endoglin monoclonal antibody in astrocytic tumors: comparison with an anti-CD31 monoclonal antibody. Neuropathology 25:201–206

    Article  PubMed  Google Scholar 

  23. Zhao W-L, Mourah S, Mounier N, Lebouef C, Daneshpousy ME, Legres L, Meignin V, Oksenhendler E, Le Maignin C, Calvo F, Briere J, Gisselbrecht C, Janin A (2004) Vascular endothelial growth factor-A is expressed both on lymphoma cells and endothelial cells in angioimmunoblastic T-cell lymphoma and related lymphoma progression. Lab Invest 84:1512–1519

    Article  PubMed  CAS  Google Scholar 

  24. Stewart M, Talks K, Leek R, Turley H, Pezzella F, Harris A, Gatter K (2002) Expression of angiogenic factors and hypoxia inducible HIF 1, HIF2, and CA IX in non-Hodgkin’s lymphoma. Histopathology 40:253–260

    Article  PubMed  CAS  Google Scholar 

  25. Roser F, Saini M, Meliss R, Ostertag H, Samii M, Bellinzona M (2004) Apoptosis, vascularity, and proliferation in primary central nervous system lymphomas: a histopathological study. Surg Neurol 62:393–399

    Article  PubMed  Google Scholar 

  26. Duff SE, LI C, Garland JM, Kumar S (2003) CD105 is important for angiogenesis: evidence and potential applications. FASEB 17:984–992

    Article  CAS  Google Scholar 

  27. Russel DS, Rubinstein LJ (1989) Primary cerebral lymphomas. In: Russel DS, Rubinstein LJ (eds) Pathology of tumours of the nervous system. Williams & Wilkins, Baltimore, pp 592–608

    Google Scholar 

Download references

Acknowledgement

We thank Mr. Fumihiro Mutoh for his valuable technical assistance.

Author information

Authors and Affiliations

  1. Department of Pathology and Biodefense, Faculty of Medicine, Saga University, Saga, Japan

    Yasuo Sugita, Yukari Takase, Daisuke Mori & Osamu Tokunaga

  2. Department of Pathology, Fukuoka Saisekai General Hospital, Fukuoka, Japan

    Akihiko Nakashima

  3. Departments of Neurosurgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan

    Minoru Shigemori

  4. Department of Pathology, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka, Japan

    Yasuo Sugita

Authors
  1. Yasuo Sugita
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yukari Takase
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daisuke Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Osamu Tokunaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akihiko Nakashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Minoru Shigemori
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasuo Sugita.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sugita, Y., Takase, Y., Mori, D. et al. Endoglin (CD 105) is expressed on endothelial cells in the primary central nervous system lymphomas and correlates with survival. J Neurooncol 82, 249–256 (2007). https://doi.org/10.1007/s11060-006-9281-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-006-9281-3

Keywords

Search

Navigation