title: Elevated levels of tumour endothelial marker-8 in human breast cancer and its clinical significance.
abstract: Tumour endothelial marker-8 (TEM-8) belongs to a family of endothelial markers that are raised during tumour angiogenesis. We have recently reported aberrant expression of TEMs at the mRNA level in human breast cancer. This study sought to examine the level of TEM-8 expression at the protein and mRNA level in human breast cancer tissue, and in a panel of human breast cancer cell lines. We also wished to determine if TEM-8 can be used as a suitable marker for identifying tumour associated micro-vessels. At the mRNA level more tumours showed positive TEM-8 expression compared to normal background tissue. TEM-8 was detected in a variety of breast cancer cell lines, endothelial cells (HECV) and in a human fibroblast cell line (MRC5) at both the mRNA and protein level. Using immunohistochemistry the distribution of TEM-8 staining was more widespread in invasive breast cancer tissue compared to normal background tissue. Furthermore, the TEM-8 marker was found to be more discriminatory in identifying micro-vessels in tumour endothelium (2.8+/-0.83 vs. normal 1.66+/-0.52; P<0.011), compared to the vWFA marker (1.61+/-0.54 vs. normal 2.71+/-0.76; P<0.009). Raised levels of TEM-8 were associated with shorter survival outcome, but were not correlated to disease-free survival as shown by Kaplan-Meier and Cox regression analysis. We conclude that TEM-8 is a useful marker for identifying tumour associated micro-vessels and that elevated levels are associated with disease progression, which may have some bearing on the prognostic outcome in breast cancer.
authors.affiliation: Metastasis & Angiogenesis Research Group, Department of Surgery, Wales College of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.
authors.forename: Gaynor
authors.initials: G
authors.lastname: Davies
authors.forename: Khaled A
authors.initials: KA
authors.lastname: Rmali
authors.forename: Gareth
authors.initials: G
authors.lastname: Watkins
authors.forename: Robert E
authors.initials: RE
authors.lastname: Mansel
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000098:blood supply* / Q000175:diagnosis* / Q000473:pathology; D002196:Capillaries / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C473287:ANTXR1 protein, human; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface