THE ANGIOGENIC FACTOR PLATELET-DERIVED ENDOTHELIAL-CELL GROWTH-FACTORTHYMIDINE PHOSPHORYLASE IS UP-REGULATED IN BREAST-CANCER EPITHELIUM AND ENDOTHELIUM

Tumour angiogenesis is a complex multistep process regulated by a numb er of angiogenic factors. One such factor, platelet-derived endothelia l cell growth factor has recently been shown to be thymidine phosphory lase (TP). TP catalyses the reversible phosphorylation of thymidine to deoxyribose-1-phosphate and thymine. Although known to be generally e levated in tumours, the expression of this enzyme in breast carcinomas is unknown. Therefore, we used ribonuclease protection assays and imm unohistochemistry to examine the expression of TP in 240 primary breas t carcinomas. Nuclear and/or cytoplasmic TP expression was observed in the neoplastic tumour epithelium in 53% of tumours. Immunoreactivity was also often present in the stromal, inflammatory and endothelial ce ll elements. Although endothelial cell staining was usually focal, imm unoreactivity was observed in 61% of tumours and was prominent at the tumour periphery, an area where tumour angiogenesis is most active. Tu mour cell TP expression was significantly inversely correlated with gr ade (P=0.05) and size (P=0.003) but no association was observed with o ther tumour variables. These findings suggest that TP is important for remodelling the existing vasculature early in tumour development, con sistent with its chemotactic non-mitogenic properties, and that additi onal angiogenic factors are more important for other angiogenic proces ses like endothelial cell proliferation. Relapse-free survival was hig her in node-positive patients with elevated TP (P=0.05) but not in oth er patient groups. This might be due to the potentiation of chemothera peutic agents like methotrexate by TP. Therefore, this enzyme might be a prediction marker for response to chemotherapy.