Prognostic value of tumour endothelial marker-8 in patients with breast cancer

ABSTRACT

Tumour angiogenesis is a critical step in the growth, metastatic spread, and re-growth of many cancers. Tumour endothelial marker 8 [TEM-8] is a newly discovered molecule belongs to a family of endothelial markers that are raised during tumour angiogenesis. This study sought to examine the level of TEM-8 expression at the protein and mRNA level in human breast cancer tissues, and in a panel of human breast cancer cell lines, and also 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 tissues. TEM-8 was detected in a variety of breast cancer cell lines, endothelial cells [HEC V] 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 tissues compared to normal background tissues. 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. [Abbreviations ATR- antrax toxin receptor, cDNA -complementary dexoyribonucleic acid; EF-edema factor; LF- lethal factor; LeTx-lethal toxin; mRNA-messenger ribonucleic acid; PCR- polymerase chain reaction; Q-RT-PCR- quantitative real time polymerase chain reaction; RNA-ribonucleic acid; TEM-8 tumour endothelial marker-8]