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Endothelin-1-, Endothelin-A-, and Endothelin-B-Receptor Expression Is Correlated with Vascular Endothelial Growth Factor Expression and Angiogenesis in Breast Cancer
Purpose: Endothelin-1 (ET-1) and its receptors (ET A R and ET B R), referred to as the endothelin (ET) axis, are overexpressed in breast carcinomas, and influence tumorigenesis and tumor progression by various mechanisms, including angiogenesis. The objective of the study was to clarify if expressio...
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Published in: | Clinical cancer research 2004-04, Vol.10 (7), p.2393-2400 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Purpose: Endothelin-1 (ET-1) and its receptors (ET A R and ET B R), referred to as the endothelin (ET) axis, are overexpressed in breast carcinomas, and influence tumorigenesis and tumor
progression by various mechanisms, including angiogenesis. The objective of the study was to clarify if expression of the
ET axis participates in angiogenesis of breast carcinoma
Experimental Design: We analyzed expression of ET-1, ET A R, ET B R, and vascular endothelial growth factor (VEGF) immunohistochemically in 600 tissue array specimens from 200 paraffin-embedded
breast carcinomas performing tissue microarray technology. Microvessel density (MVD) was determined by counting microvessels
(identified by factor VIII) in each core specimen.
Results: Moderate or strong immunostaining was observed for ET-1 in 25.4%, for ET A R in 43.7%, and for ET B R in 22.2% of breast carcinomas. Of all cases, 44.7% showed significant expression of VEGF. MVD varied between different tumor
specimens (range, 0–80; median, 17). We observed a statistically significant correlation between MVD and ET expression status
with higher MVD in ET-positive tumors. Moreover, expression of VEGF was found more frequently in tumors with overexpression
of the ET axis (each P < 0.001). Staining of VEGF was correlated positively with MVD
Conclusions: These results indicate that increased ET-1, ET A R, and ET B R expression is associated with increased VEGF expression and higher vascularity of breast carcinomas and, thus, could be
involved in the regulation of angiogenesis in breast cancer. Our findings provide evidence that the expression pattern of
the ET-axis and in particular of ET A R may have clinical relevance in future antiangiogenic targeted therapies for breast cancer. |
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ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-03-0115 |