Over-expression of endoglin (CD105): A marker of breast carcinoma-induced neo-vascularization

The commencement of the complex process of carcinogenesis, and subsequent, rapid tumor growth and progression of mammalian neoplasms, including breast carcinomas (BCs), depends upon the continuous de novo formation of capilla ries [i.e. neovascularization (NV)/neoplasm-related angiogenesis (NRA)]. Th e generation of a malignant, invasive cellular immunophenotype (CIP) and di stant metastases, as aspects of tumor progression, are also NRA-dependent p rocesses. Endothelial cells undergo rapid proliferation during mammary carc inoma- related angiogenesis. Human endoglin (CD105/EDG), is a homodimeric c ell surface component of the transforming growth factor-beta (TGF-beta) typ e I receptor complex and is also a proliferation- associated antigen (PM) e xpressed at high density on endothelial cells. Formalin fixed, paraffin-wax embedded, tissue sections (3-5 mu m thick) of 15 BCs were employed for the assessment of EDG expression. An indirect, four-step, alkaline phosphatase (AP) (or diaminobenzidine [DAB]) conjugated biotin-streptavidin based, ant igen detection technique, employing the SN6h anti-EDG monoclonal antibody w as conducted. Zymed's Histogold(TM) System was also utilized for immunocyto logical antigen detection. Strong expression (A; +++ to ++++) of EDG on end othelial cells was demonstrated in all 15 BC cases. The most striking featu re of the newly formed neoplasm-related capillaries was the presence of an enlarged perivascular space. Blood vessels in several normal human tissues (cortex, cerebellum, thymus, tonsil, spleen, lymph node, skin) used as cont rol tissues contained significantly lower levels of EDG (B and mostly C; +/ - to +), in accordance with the extremely slow turnover rare of normal endo thelial cells. Furthermore, a close apposition between the capillaries and the adjacent parenchyma was observed in these normal controls. BCs, as most mammalian neoplasms, are characterized by extensive neovascularization and thus are candidates for anti-angiogenic therapy. Further studies should su bstantiate the importance of EDG expression in the earliest possible detect ion, diagnosis and NRA inhibition-based treatment of solid tumors, includin g BCs.