Levels of expression of endothelial markers specific to tumour-associated endothelial cells and their correlation with prognosis in patients with breast cancer

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.

An Integrative Approach Uncovers Biomarkers that Associate with Clinically Relevant Disease Outcomes in Vulvar Carcinoma

“…Although PLXDC2 is usually upregulated with PLXDC1 in stromal endothelial cells of several tumors, such as colorectal cancer (25), it does not appear to govern endothelial cell morphogenesis in these tumors like PLXDC1 (25). Instead, PLXDC2 participates in apoptosis and cellcycle arrest (26) and is also associated with poor outcomes, a worse prognosis, and lymph node metastasis in breast cancer (27). Regardless of the increasing association of this gene with tumor behavior, its function and interactions have not been examined.…”

Hypoxia upregulates expression of human endosialin gene via hypoxia-inducible factor 2

“…However, the molecular mechanisms that control endosialin expression have remained elusive (Rettig et al, 1992;Brady et al, 2004;Davies et al, 2004;Madden et al, 2004;Dolznig et al, 2005;MacFadyen et al, 2005;Huber et al, 2006).…”

“…Subsequent studies have confirmed that endosialin is upregulated in blood vessels and activated stromal fibroblasts in human colorectal, brain and breast tumours as well as in mouse xenograft models (Carson-Walter et al, 2001;Brady et al, 2004;Davies et al, 2004;Madden et al, 2004;Dolznig et al, 2005;MacFadyen et al, 2005MacFadyen et al, , 2007Huber et al, 2006;Rupp et al, 2006). Endosialin expression is restricted to capillaries and shows a heterogeneous pattern typical for molecules involved in vascular reorganisation.…”

Novel surface targets and serum biomarkers from the ovarian cancer vasculature

“…This does not diminish their potential importance as tumor vascular markers or therapeutic targets in a subset of patients. Importantly, this is the case for tumor vascular markers that have already been validated and are currently being developed as therapeutic targets, e.g., TEM1, 34 for which therapeutic antibodies are already under early phase clinical testing. Ideally, for the purpose of tumor detection, development of molecular imaging tools should focus on genes that are highly expressed in most EOC tumors.…”