Abstract
Tumour endothelial markers (TEMs) are a newly discovered family of endothelial markers associated with tumour specific angiogenesis. This study sought to examine the levels of expression for TEMs in human breast cancer. Breast cancer tissues (n=120) together with normal background tissues (n=33) were obtained after surgery. RNA was extracted from frozen sections for gene amplification. The expression of TEMs was assessed using RT-PCR and the quantity of their transcripts was determined using real-time-quantitative PCR (Q-RT-PCR). TEM-7R (P=0.05) and TEM-8 (P<0.01) were significantly raised in breast cancer tissues compared with the levels detected in normal background tissues. After a median follow-up of 72.2 months it was found that patients who had recurrent disease and/or who had died from breast cancer had a significantly (P<0.05) elevated level of TEM-1 compared to those patients who were disease free. In addition, elevated levels of TEM-4, TEM-5, TEM-6, TEM-7 and TEM-7R were also raised in breast cancer tissues. Patients who had developed nodal involvement exhibited significantly (P<0.05) high levels of TEM-1 and TEM-7R compared to patients who were node negative. Furthermore, the levels of TEMs did not correlate with tumour or histological grade. We conclude that elevated levels of TEM-1, TEM-7R and TEM-8 (but not TEM-2, 4, 5, 6 and 7) are associated with either nodal involvement, and/or disease progression, and may therefore, have a prognostic value in breast cancer.
Similar content being viewed by others
References
Fisher B, Bauer M, Wickerham DL et al. Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update. Cancer1983; 52: 1551–7.
Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer 1989; 63: 181–7.
Forbes JF. The incidence of breast cancer: The global burden, public health considerations. Semin Oncol 1997; 24: 20–35.
Cunnick GH, Jiang WG, Gomez KF et al. Lymphangiogenesis and breast cancer metastasis. Histol Histopathol 2002; 17: 863–70.
Jiang WG, Martin TA, Mansel RE. Molecular detection of microymetastasis in breast cancer. Crit Rev Oncol Hematol 2002; 43: 13–31.
Weidner N, Semple JP, Welch WR et al. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N Engl J Med 1991; 324:1–8.
Jussila L, Alitalo K. Vascular growth factors and lymphangiogenesis. Physiol Rev2002; 82: 673–700.
Tanaka F, Otake Y, Yanagihara K et al. Evaluation of angiogenesis in non-small cell lung cancer: comparison between anti-CD34 antibody and anti-CD105 antibody. Clin Cancer Res 2001; 7: 3410–5.
Rice A, Quinn CM. Angiogenesis, thrombospondin, and ductal carcinoma in situ of the breast. J Clin Pathol 2002; 55: 569–74.
Papetti M, Herman IM. Mechanisms of normal and tumor-derived angiogenesis. Am J Physiol Cell Physiol 2002; 282: C947–C70.
'Reilly MS, Holmgren L, Shing Y et al. Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994; 79: 315–28.
Folkman J. Seminars in Medicine of the Beth Israel Hospital, Boston. Clinical applications of research on angiogenesis. N Engl JMed 1995;333: 1757–63.
Maglione D, Guerriero V, Viglietto G et al. Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. Proc Natl Acad Sci USA 1991; 88: 9267–71.
O'Reilly MS, Boehm T, Shing Y et al. Endostatin: An endogenous inhibitor of angiogenesis and tumor growth. Cell 1997; 88: 277–85.
Senger DR, Galli SJ, Dvorak AM et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983; 219: 983–5.
Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Comm 1989; 161: 851–8.
Gospodarowicz D, Abraham JA, Schilling J. Isolation and characterization of a vascular endothelial cell mitogen produced by pituitaryderived folliculo stellate cells. Proc Natl Acad Sci USA 1989; 86: 7311–5.
Solovey AN, Gui L, Chang L et al. Identification and functional assessment of endothelial P1H12. J Lab Clin Med 2001; 138: 322–31.
St Croix B, Rago C, Velculescu V et al. Genes expressed in human tumor endothelium. Science 2000;289: 1197–202.
Teo NB, Shoker BS, Jarvis C et al. Vascular density and phenotype around ductal carcinoma in situ (DCIS) of the breast. Br J Cancer 2002; 86: 905–11.
Carson-Walter EB, Watkins DN, Nanda A et al. Cell surface tumor endothelial markers are conserved in mice and humans. Cancer Res 2001; 61: 6649–55.
Jiang WG, Douglas-Jones A, Mansel RE. Expression of peroxisomeproliferator activated receptor-gamma (PPAR?) and the PPAR? coactivator, PGC-1, in human breast cancer correlates with clinical outcomes. Int J Cancer 2003; 106: 752–7.
Parr C, Jiang WG. Quantitative analysis of lymphangiogenesis in human colon cancer. Int J Oncol 2003; 23: 533–9.
Davies G, Mason MD, Martin TA et al. The HGF/SF antagonist NK4 reverses fibroblast-and HGF-induced prostate tumor growth and angiogenesis in vivo. Int J Cancer 2003; 106: 348–54.
Nakamura Y, Yasuoka H, Tsujimoto M et al. Prognostic significance of vascular endothelial growth factor d in breast carcinoma with longterm follow-up. Clin Cancer Res2003; 9: 716–21.
Feldman AL, Libutti SK. Progress in antiangiogenic gene therapy of cancer. Cancer 2000; 89: 1181–94.
Colombatti A, Bonaldo P. The superfamily of proteins with von Willebrand factor type A-like domains: one theme common to components of extracellular matrix, hemostasis, cellular adhesion, and defense mechanisms. Blood 1991; 77: 2305–15.
Lee JO, Rieu P, Arnaout MA et al. Crystal structure of the A domain from the alpha subunit of integrin CR3 (CD11b/CD18). Cell 1995; 80: 631–8.
Dickeson SK, Santoro SA. Ligand recognition by the I domaincontaining integrins. Cell Mol Life Sci1998; 54: 556–66.
Van der Vieren M, Crowe DT, Hoekstra D et al. The leukocyte integrin alpha D beta 2 binds VCAM-1: evidence for a binding interface between I domain and VCAM-1. J Immunol 1999; 163: 1984–90.
Hood JD, Cheresh DA. Role of integrins in cell invasion and migration. Nat Rev Cancer 2002; 2: 91–100.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Davies, G., Cunnick, G.H., Mansel, R.E. et al. Levels of expression of endothelial markers specific to tumour-associated endothelial cells and their correlation with prognosis in patients with breast cancer. Clin Exp Metastasis 21, 31–37 (2004). https://doi.org/10.1023/B:CLIN.0000017168.83616.d0
Issue Date:
DOI: https://doi.org/10.1023/B:CLIN.0000017168.83616.d0