ENDOTHELIAL TIE GROWTH-FACTOR RECEPTOR PROVIDES ANTIGENIC MARKER FOR ASSESSMENT OF BREAST-CANCER ANGIOGENESIS

Breast cancer prognosis has previously been linked to the degree of tu mour vascularisation. In order to establish additional markers for tum our angiogenesis, we have used monoclonal antibodies against the endot helial Tie receptor tyrosine kinase to study the degree of vascularisa tion of breast carcinomas and the regulation of Tie expression in the vascular endothelial cells. Antibodies were used for Tie detection and the results were correlated with other prognostic markers. Of four mo noclonal antibodies directed against different epitopes of the Tie ext racellular domain, two reacted against Tie in unfixed histopathologica l sections of breast Carcinomas. One of these antibodies (clone 7e8) w as specific for the endothelial cells whereas the other (clone 10f11) also reacted with basement membranes and occasional carcinoma cells. W hen Tie expression was studied with the antibody clone 7e8, all 27 car cinomas, two in situ carcinomas, samples of histologically normal brea st tissue (n = 16) or normal skin or lymph node tissue (n = 5) showed staining. Microvessel counts were higher in carcinomas (median 14; ran ge 3-27) than in fibrodenomas (median 10; range 5-18) or histologicall y normal breast tissue (median 7; range 3-15, P = 0.0006). A similar r esult was obtained using antibodies against the CD31 (PECAM) antigen. Microvessel counts in 7e8 staining were not significantly associated w ith primary tumour size, axillary nodal status, histological grade or staining for oestrogen receptor, progesterone receptor, Ki-67 prolifer ation marker or p53 oncoprotein.