Document Type : Original Research


Dept. of Pathology, Isfahan University of Medical Sciences, Isfahan, Iran.



Background and Objectives: Angiogenesis is essential for growth and metastasis of solid malignancies. Tumor vessel count and expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, have been associated with prognosis. This study was designed to assess vessels density by using CD31 and CD105 (Endoglin) and their correlation with expression of VEGF and proliferative index (Ki67) in Glioblastoma multiforme (GBM). Methods: We examined these parameters in GBM specimens from 50 adult patients; referred to AlZahra hospital Pathology Lab between 2001 to 2006.These patients did not receive pre-operative therapy.  Paraffin-embedded  tumor  specimens  were  immunohistochemically  stained  for  CD31, CD105 (Endoglin), VEGF and Ki67 (proliferation index) monoclonal antibodies. Microvessel density (MVD) was evaluated by immunostaining for CD31 and CD105.Then the results were compared between the two and also with VEGF receptors and Ki67 index. Results: CD105-MVD was significantly higher in Glioblastoma compared with peritumoral normal (14.28 vs. 6.68: P=0.012). We did not find such difference for CD31. The mean of CD105-MVD was significantly higher than CD31-MVD in Glioblastoma tissue (P<0.001) although there was a significant positive relationship between them (Pearson’s r=0.630 P<0.001).The VEGF scoring for tumoral tissue was 12 % (score:1), 46% (score:2) and 42% (score:3).For peritumoral normal tissue were 92% (score:1) and 8% (score:2) . So they reach to statistical significance (Chi Square, P= 001). Both MVD of CD105 and CD31 have significant relationship with VEGF (P<0.001). Conclusion: We suggest that Endoglin can be used as a specific and sensitive marker for evaluation of angiogenesis in Glioblastoma.


  1. Galan-Moya EM, Le Guelte A, Lima Fernandes E, ThirantC, Dwyer J, Bidere N, et al. Secreted factors from  brain  endothelial  cells  maintain  glioblastoma stem-like cell expansion through the mTOR pathway. EMBO Rep 2011;12(5):470-6.
  2. Smith SJ, Tilly H, Ward JH, Macarthur DC, Lowe J, Coyle B, et al. CD105 (Endoglin) exerts prognostic effects via its role in the microvascular niche of paediatric high grade glioma. Acta Neuropatho 2012; 124(1):99-10.
  3. Ricci-Vitiani L, Pallini R, Biffoni M, Todaro M, Invernici G, Cenci T, et al.Tumor vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature 2010;468(7325):824-8.
  4. Furnari  FB,  Fenton  T,  Bachoo  RM,  Mukasa  A, Stommel  JM,  Stegh  A,  et  al.  Malignant  astrocyticglioma: genetics, biology, and paths to treatment. Genes Dev 2007;21(21):2683-710.
  5. Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 2007; 25(11):2739-49.
  6. Netto GC, Bleil CB, Hilbig A, Coutinho LM. Immunohistochemical evaluation of the microvascular density through the expression of TGF-beta (CD 105/endoglin) and CD 34 receptors and expression of the vascular endothelial growth factor (VEGF) in oligodendrogliomas. Neuropathology 2008;28(1):17-23.
  7. Birlik B, Canda S, Ozer E. Tumour vascularity is  of  prognostic  significance  in  adult,  but  not paediatric astrocytomas. Neuropathol Appl Neurobiol 2006;32(5):532-8.
  8. Behrem S, Zarkovic K, Eskinja N, Jonjic N. Endoglin is a better marker than CD31 in evaluation of angiogenesis in glioblastoma. Croat Med J 2005 ;46(3):417-22.
  9. Batchelor TT, Duda DG, di Tomaso E, Ancukiewicz M, Plotkin SR, Gerstner E, et al.Phase II study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. J Clin Oncol 2010;28(17):2817-23.
  10. Rahman R, Smith S, Rahman C, Grundy R. Antiangiogenic therapy and mechanisms of tumor resistance in malignant glioma. J Oncol 2010;2010:251231.
  11. Fonsatti E, Nicolay HJ, Altomonte M, Covre A, Maio M. Targeting cancer vasculature via endoglin/CD105: a novel antibody-based diagnostic and therapeutic strategy in solid tumors. Cardiovasc Res 2010;86(1):12-9.
  12. Saad RS, El-Gohary Y, Memari E, Liu YL, Silverman JF Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in esophageal adenocarcinoma. Hum Pathol 2005;36(9):955-61.
  13. Kayaselçuk F, Zorludemir S, Gümürdühü D, Zeren H, Erman T. PCNA and Ki-67 in central nervous system tumors: correlation with the histological type and grade. J Neurooncol 2002;57(2):115-21.
  14. Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat 1995;36(2):169-80.
  15. Barresi V, Cerasoli S, Vitarelli E, Tuccari G. Density of microvessels positive for CD105 (endoglin) is related to prognosis in meningiomas. Acta Neuropathol 2007; 114(2):147-56.
  16. Minhajat R, Mori D, Yamasaki F, Sugita Y, Satoh T,  Tokunaga  O.  Organ-specific  endoglin  (CD105) expression in the angiogenesis of human cancers. Pathol Int 2006;56(12):717-23.
  17. Dallago CM, Oliveira MC, Barbosa-Coutinho LM, Ferreira NP. Angiogenesis in craniopharyngiomas: Microvascular density and tissue expression of the vascular endothelial growth factor (VEGF) and endostatin. Endocr Pathol 2005 ;16(4):355-62.
  18. Yao Y, Kubota T, Takeuchi H, Sato K. Prognostic significance  of  microvessel  density  determined  by  an anti-CD105/endoglin monoclonal antibody in astrocytic tumors: comparison with an anti-CD31 monoclonal antibody. Neuropathology 2005;25(3):201-6.
  19. Mikalsen LT, Dhakal HP, Bruland OS, Nesland JM,  Olsen  DR.  Quantification  of  angiogenesis  in breast  cancer  by  automated  vessel  identification  in CD34 immunohistochemical sections. Anticancer Res 2011;31(12):4053-60.
  20. Tanaka F, Otake Y, Yanagihara K, Kawano Y, Miyahara R, Li M, et al.Evaluation of angiogenesis in non-small cell lung cancer: comparison between antiCD34 antibody and anti-CD105 antibody. Clin Cancer Res 2001 ;7(11):3410-5.
  21. Behrem S, Zarkovic K, Eskinja N, Jonjic N. Endoglin is a better marker than CD31 in evaluation of angiogenesis in glioblastoma. Croat Med J 2005;46(3):417-22.
  22. Yao Y, Pan Y, Chen J, Sun X, Qiu Y, Ding Y. Endoglin (CD105) expression in angiogenesis of primary hepatocellular carcinomas: analysis using tissue microarrays and comparisons with CD34 and VEGF. Ann Clin Lab Sci 2007;37(1):39-48.
  23. Minhajat R, Mori D, Yamasaki F, Sugita Y, Satoh T, Tokunaga O. Endoglin (CD105) expression in angiogenesis of colon cancer: analysis using tissue microarrays and comparison with other endothelial markers. Virchows Arch 2006;448(2):127-34.
  24. Gohary YM, Silverman JF, Olson PR, Liu YL, Cohen JK, Miller R, et al.Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in prostatic adenocarcinoma. Am J Clin Pathol 2007;127(4):572-9.
  25. Raica M, Cimpean AM, Anghel A. Immunohistochemical expression of vascular endothelial growth factor (VEGF) does not correlate with microvessel density in renal cell carcinoma. Neoplasia 2007;54(4):278-84.
  26. Gupta K, Radotra BD, Banerjee AK, Nijhawan R. Quantitation of angiogenesis and its correlation with vascular endothelial growth factor expression in astrocytic tumors. Anal Quant Cytol Histol 2004 ; 26(4):223-9.
  27. Lebelt  A,  Dziecioł  J,  Guzińska-Ustymowicz  K, Lemancewicz D, Zimnoch L, Czykier E, et al.Angiogenesis in gliomas. Folia Histochem Cytobiol 2008; 46(1):69-72.