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Up-regulation of thymidine phosphorylase expression is associated with a discrete pattern of angiogenesis in ductal carcinomasin situ of the breast

✍ Scribed by Engels, K.; Fox, S. B.; Whitehouse, R. M.; Gatter, K. C.; Harris, A. L.


Publisher
John Wiley and Sons
Year
1997
Tongue
English
Weight
860 KB
Volume
182
Category
Article
ISSN
0022-3417

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✦ Synopsis


Angiogenesis is essential for tumour growth and metastasis. Although vascular density as a measure of angiogenesis is an important prognostic factor in invasive breast carcinoma, the mechanism of a switch to an angiogenic phenotype in ductal in situ breast carcinomas (DCIS) has yet to be identified. Nevertheless, two distinct vascular patterns have been reported in DCIS: a diffuse increase of stromal vascularity and a dense rim of microvessels close to the basement membrane of involved ducts. This suggests that tumour angiogenesis in invasive breast cancer arises from two different angiogenic pathways. Platelet-derived endothelial cell growth factor, now known to be thymidine phosphorylase (TP), is a candidate for initiating one of these pathways, since it is important in remodelling the existing vasculature through its chemotactic non-mitogenic properties and is expressed early in breast cancer development. The expression of TP was therefore examined in 75 formalin-fixed, paraffin-embedded specimens of DCIS by immunohistochemistry, using the monoclonal antibody PGF44c to detect TP. The results were correlated with blood vessel staining by polyclonal antibodies to von Willebrand factor (Factor VIII-related antigen, FVIIIrAg) and other clinicopathological variables. TP expression was nuclear and/or cytoplasmic and was observed in all subtypes of DCIS. High TP expression was demonstrated in 36 per cent (27/75) of tumours. This was not limited to the neoplastic cells, but was also present in stroma, endothelium, and tumour-associated macrophages. There was no correlation between high TP and DCIS subtype (P>0•05). There was a significant correlation between TP expression and the presence of a dense vascular rim (P=0•042; 2 =4•1), but not with an increase in stromal vascularity (P=0•800; 2 =0•1). There was no significant correlation between tumour TP expression and relapse-free survival (P=0•662; 2 =0•2). These findings suggest that remodelling of the pre-existing vascular network induced by TP is important in generating a dense rim of microvessels around DCIS. 1997 by John Wiley & Sons, Ltd.


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Angiogenesis and expression of thymidine
✍ Lee, Andrew H. S.; Dublin, Edwin A.; Bobrow, Lynda G. 📂 Article 📅 1999 🏛 John Wiley and Sons 🌐 English ⚖ 312 KB 👁 2 views

Angiogenesis is essential for tumour growth and important in metastasis and for prognosis in invasive carcinoma of the breast. Two patterns of increased vascularity have been shown in mammary ductal carcinoma in situ (DCIS): a cuff of vessels close to the involved ducts, and vessels in the interduct