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 v ascular density, as a measure of angiogenesis is an important prognost ic factor in invasive breast carcinoma, the mechanism of a snitch to a n angiogenic phenotype in ductal in situ breast carcinomas (DCIS) has Set to be identified, Nevertheless, two distinct vascular patterns hav e been reported in DCIS: a diffuse increase of stromal vascularity and a dense rim of microvessels close to the basement membrane of involve d ducts, This suggests that tumour angiogenesis in invasive breast can cer arises from two different angiogenic pathways, Platelet-derived en dothelial 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 chemota ctic non-mitogenic properties and is expressed early in breast cancer development; The expression of TP was therefore examined in 75 formali n-fixed, paraffin-embedded specimens of DCIS by immunohistochemistry , using the monoclonal antibody PGF44c to detect TP, The results mere c orrelated with blood, vessel staining by polyclonal antibodies to von Willebrand factor (Factor Vm-related antigen, FVIIIrAg) and other clin icopathological variables, TP expression was nuclear and/or cytoplasmi c and was observed in all subtypes of DCIS, High TP expression was dem onstrated in 36 per cent (27/75) of tumours, This was not limited to t he neoplastic cells, but was also present in stroma, endothelium, and tumour-associated macrophages. There was no correlation between high T P and DCIS subtype (P>0.05). There was a significant correlation betwe en TP expression and the presence of a dense vascular rim (P=0.042; ch i(2)=4.1), but not with an increase in stromal vascularity (P=0.800; c hi(2)=0.1), There was no significant correlation between tumour TP exp ression 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 D CIS. (C) 1997 by John Wiley & Sons, Ltd.