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

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 snitch to an angiogenic phenotype in ductal in situ breast carcinomas (DCIS) has Set 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 mere correlated with blood, vessel staining by polyclonal antibodies to von Willebrand factor (Factor Vm-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; chi(2)=4.1), but not with an increase in stromal vascularity (P=0.800; chi(2)=0.1), There was no significant correlation between tumour TP expression and relapse-free survival (P=0.662; chi(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. (C) 1997 by John Wiley & Sons, Ltd.