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01-08-2007 | Original Paper

Density of microvessels positive for CD105 (endoglin) is related to prognosis in meningiomas

Authors: Valeria Barresi, Serenella Cerasoli, Enrica Vitarelli, Giovanni Tuccari

Published in: Acta Neuropathologica | Issue 2/2007

Abstract

Microvessel density (MVD) is considered to be a prognostic marker in many tumours. Nevertheless, conflicting results were achieved regarding its prognostic role in meningiomas when it was quantified through pan-endothelial markers such as CD34, CD31 or Factor VIII. In the present study, MVD was assessed in meningiomas through the specific marker for neo-angiogenesis CD105. Fifty-four formalin fixed, paraffin embedded, surgical cases of meningiomas (WHO 28 grade I and 26 grade II) as well as ten normal leptomeningeal samples were submitted to immunohistochemical analysis for CD105. CD34 immuno-expression was also evaluated on consecutive parallel sections. For each case, MVD was estimated in terms of number of vessels/mm². CD105 was not evidenced in normal samples, whereas it was demonstrated in the vessels within 14/28 WHO grade I cases and within 24/26 WHO grade II meningiomas. On the contrary, CD34 antibody stained blood vessels in both normal and neoplastic samples; moreover, in each case, it stained more microvessels than CD105 antibody (25.33 ± 21.16 vs. 50.72 ± 26.75). Higher CD105 counts were significantly correlated with higher histological grade and Ki-67 LI > 4%. No statistical significant correlations were encountered between MVD measured by either CD105 and CD34 and sex, age, site of tumour or extent of surgical resection. CD105-MVD, but not CD34-MVD, showed an inverse significant correlation with overall survival and recurrence-free survival. In conclusion, our study suggests the higher specificity of CD105 in comparison to pan-endothelial markers in the evaluation of meningioma neo-angiogenesis, and its higher prognostic significance. CD105 might serve as a target for therapeutic approaches blocking blood supply in meningiomas.

Adam PJ, Clesham GJ, Weissberg PL (1998) Expression of endoglin m-RNA and protein in human vascular smooth muscle cells. Biochem Byophis Res Commun 247:33–37CrossRef

Assimakopoulou M, Sotiropoulou-Bonikou G, Maraziotis T, Papadakis N, Varakis I (1997) Microvessel density in brain tumors. Anticancer Res 17:4747–4753PubMed

Barresi V, Cerasoli S, Paioli G, Vitarelli E, Giuffrè G, Tuccari G, Barresi G (2006) Caveolin-1 in meningiomas: expression and clinico-pathological correlations. Acta Neuropathol 112:617–626PubMedCrossRef

Behrem S, Zrkovic K, Eskina N, Jonjic N (2005) Endoglin is a better marker than CD31 in evaluation of angiogenesis in glioblastoma. Croat Med J 46:417–422PubMed

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

Burrows FJ, Derbyshire EJ, Tazzari PL, Amlot P, Gazdar AF, King SW, Letarte M, Vitetta ES, Thorpe PE (1995) Up-regulation of endoglin on vascular endothelial cells in human solid tumours: implications for diagnosis and therapy. Clin Cancer Res 1:1623–1634PubMed

Cheifetz S, Bellon T, Cales C, Vera S, Bernabeu C, Massague J, Letarte M (1992) Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells. J Biol Chem 267:19027–19030PubMed

Christov C, Lechapt-Zalcman E, Adle-Biassette H, Nachev S, Gherardi RK (1999) Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) and its receptor flt-1 in microcystic meningiomas. Acta Neuropathol 98:414–420PubMedCrossRef

Dallago CM, Oliveira MC, Barbosa-Coutinho LM, Ferreira NP (2005) Angiogenesis in craniopharyngiomas: microvascular density and tissue expression of the vascular endothelial growth factor (VEGF) and endostatin. Endocr Pathol 16:355–362PubMedCrossRef

10.

Ding S, Li C, Lin S, Yang Y, Liu D, Han Y, Zhang Y, Li L, Zhou L, Kumar S (2006) Comparative evaluation of microvessel density determined by CD34 or CD105 in benign and malignant gastric lesions. Hum Pathol 37:861–866PubMedCrossRef

11.

Folkman J (1990) What is the evidence that tumour are angiogenesis dependent? J Natl Cancer Inst 82:4–6PubMedCrossRef

12.

Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267:10931–10934PubMed

13.

Folkman J (1995) Clinical applications of angiogenesis research. N Engl J Med 333:1757–1763PubMedCrossRef

14.

Gougos A, St Jacques S, Greaves A, O’Connell PJ, d’Apice AJ, Buhring HJ, Bernabeu C, van Mourik JA, Letarte M (1992) Identification of distinct epitopes of endoglin, an RGD-containing glycoprotein of endothelial cells, leukemic cells, and syncytiotrophoblasts. Int Immunol 4:83–92PubMedCrossRef

15.

Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364PubMedCrossRef

16.

Hlatky L, Hahnfeldt P, Folkman J (2002) Clinical application of antiangiogenic therapy: microvessel density, what it does and does not tell us. J Natl Cancer Inst 94:883–893PubMed

17.

Kleihues P, Cavenee WK (eds) (2000) Pathology and genetics of tumours of the nervous system. IARC Press, Lyon

18.

Kyzas PA, Agnantis NJ, Stefanou D (2006) Endoglin (CD105) as a prognostic factor in head and neck squamous cell carcinoma. Virchows Arch 448:768–775PubMedCrossRef

19.

Lamszus K, Lengler U, Schmidt NO, Stavrou D, Ergun S, Westphal M (2000) Vascular endothelial growth factor, hepatocyte growth factor/scatter factor, basic fibroblast growth factor, and placenta growth factor in human meningiomas and their relation to angiogenesis and malignancy. Neurosurgery 46:938–947PubMedCrossRef

20.

Lewy-Trenda I, Omulecka A, Janczukowicz J, Papierz W (2003) The morphological analysis of vasculature and angiogenic potential in meningiomas: immunoexpression of CD31 and VEGF antibodies. Folia Neuropathol 41:149–153PubMed

21.

Maiuri F, De Caro Mdel B, Esposito F, Cappabianca P, Strazzullo V, Pettinato G, de Divitiis E (2007) Recurrences of meningiomas: predictive value of pathological features and hormonal and growth factors. J Neurooncol 82:63–68PubMedCrossRef

22.

Maxwell PH, Dachs GU, Gleade JM, Nicholls LG, Harris AL, Stratford IJ, Hankinson O, Pugh CW, Ratcliffe PJ (1997) Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci USA 94: 8104–8109PubMedCrossRef

23.

Miller DW, Graulich W, Karges B, Stahl S, Ernst M, Ramaswamy A, Sedlacek HH, Muller R, Adamkiewicz J (1999) Elevated expression of endoglin, a component of the TGF-ß receptor complex, correlates with proliferation of tumour endothelial cells. Int J Cancer 81:568–572PubMedCrossRef

24.

Minhajat R, Mori D, Yamasaki F, Sugita Y, Satoh T, Tokunaga O (2006) Endoglin (CD105) expression in angiogenesis of colon cancer: analysis using tissue microarrays and comparison with other endothelial markers. Virchows Arch 448:127–134PubMedCrossRef

25.

Nishio S, Takeshita I, Morioka T, Fukui M (1994) Microcystic meningiomas: climicopathological features of 6 cases. Neurol Res 16:251–256PubMed

26.

Perry A, Stafford SL, Scheithauer BW, Suman VJ, Lohse CM (1998) The prognostic significance of MIB-1, p53, and DNA flow cytometry in completely resected primary meningiomas. Cancer 82:2262–2269PubMedCrossRef

27.

Perry A, Stafford SL, Scheithauer BW, Lohse CM, Wollan PC (1999) “Malignancy” in meningiomas: a clinico-pathological study of 116 patients with grading implications. Cancer 85:2046–2056PubMed

28.

Pistolesi S, Boldrini L, Gisfredi S, De Ieso K, Camacci T, Caniglia M, Lupi G, Leocata P, Basolo F, Pingitore R, Parenti G, Fontanini G (2004) Angiogenesis in intracranial meningiomas: immunohistochemical and molecular study. Neuropathol Appl Neurobiol 30:118–25PubMedCrossRef

29.

Provias J, Claffey K, delAguila L, Lau N, Feldkamp M, Guha A (1997) Meningiomas: role of vascular endothelial growth factor/vascular permeability factor in angiogenesis and peritumoral edema. Neurosurgery 40:1016–1026PubMedCrossRef

30.

Romani AA, Borghetti AF, Del Rio P, Sianesi M, Soliani P (2006) The risk of developing metastatic disease in colorectal cancer is related to CD105-positive vessel count. J Surg Oncol 93:446–455PubMedCrossRef

31.

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 36:955–961PubMedCrossRef

32.

Saad RS, Jasnosz KM, Silverman JF (2003) Endoglin (CD105) expression in endometrial carcinoma. Int J Gynecol Pathol 22:248–253PubMedCrossRef

33.

Sanchez-Elsner T, Botella LM, Velasco B, Langa C, Bernabeu C (2002) Endoglin expression is up-regualted by transcriptional cooperation between the hypoxia and the transforming-growth factor-beta pathways. J Biol Chem 277:43799–43808PubMedCrossRef

34.

Sandlund J, Hedberg Y, Bergh A, Grankvist K, Ljunberg B, Rasmuson T (2006) Endoglin (CD105) expression in human renal cell carcinoma. BJU Int 97:706–710PubMedCrossRef

35.

Shono T, Inamura T, Torisu M, Suzuki SO, Fukui M (2000) Vascular endothelial growth factor and malignant transformation of a meningioma: a case report. Neurol Res 22:189–193PubMed

36.

Simpson D (1957) The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 20:22–39PubMedCrossRef

37.

Sugita Y, Takase Y, Mori D, Tokunaga O, Nakashima A, Shigemori M (2006) Endoglin (CD 105) is expressed on endothelial cells in the primary central nervous system lymphomas and correlates with survival. J Neurooncol (Epub ahead of print)

38.

Torsney E, Charlton R, Parums D, Collis D, Arthur HM (2002) Inducible expression of human endoglin during inflammation and wound healing in vivo. Inflamm Res 51:464–470PubMedCrossRef

39.

Wang JM, Kumar S, Pye D, van Aghtoven AJ, Krupinski J, Hunter RD (1993) A monoclonal antibody detects heterogeneity in vacular endothelium of tumours and normal tissues. Int J Cancer 54:363–370PubMedCrossRef

40.

Wang JM, Kumar S, Pye D, Haboubi N, Al-Nakib L (1994) Breast carcinoma: a comparative study of tumour vasculature using two endothelial cell markers. J Natl Cancer Inst 86:386–388PubMedCrossRef

41.

Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma. N Engl J Med 324:1–8PubMedCrossRef

42.

Weir EE, Pretlow TG, Pitts A (1974) A more sensitive and specific histochemical peroxidase stain for the localization of cellular antigen by the enzyme-antibody conjugated method. J Histochem Cytochem 22:1135–1140PubMed

43.

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 25:201–206PubMedCrossRef

44.

Yoo H, Baia GS, Smith JS, McDermott MW, Bollen AW, Vandenberg SR, Lamborn KR, Lal A (2007) Expression of hypoxia marker carbonic anhydrase 9 is associated with anaplastic phenotypes in meningiomas. Clin Cancer Res 13:68–75PubMedCrossRef

45.

Zhu Y, Sun Y, Xie L, Jin K, Sheibani N, Greenberg DA (2003) Hypoxic induction of endoglin via mitogen-activated protein kinases in mouse brain microvascular endothelial cells. Stroke 34:2483–2488PubMedCrossRef

Title: Density of microvessels positive for CD105 (endoglin) is related to prognosis in meningiomas
Authors: Valeria Barresi
Serenella Cerasoli
Enrica Vitarelli
Giovanni Tuccari
Publication date: 01-08-2007
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 2/2007
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-007-0251-4

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Density of microvessels positive for CD105 (endoglin) is related to prognosis in meningiomas

Abstract

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