Immunohistological detection of tissue factor in normal and abnormal human mammary glands using monoclonal antibodies

Tissue factor (TF) is the primary cell-bound initiator of the coagulation protease cascade. The cytological distribution of TF in various tissues may be described on the basis of immunohistochemistry with epitope-defined monoclonal antibodies and the extravascular distribution of TF apparently represents a haemostatic envelope ready to activate coagulation when vascular integrity is disrupted. The present study localized TF in human breast cancer tissues when compared with normal breast gland tissues and benign disorders of the mammary gland. By use of a cocktail of three epitope-defined monoclonal antibodies, TF was detected only in the myoepithelia of the resting breast gland. In proliferating disorders like fibrocystic disease or in fibroadenomas, both myoepithelia and luminal epithelia showed TF expression. Of 115 breast cancers 93 reacted with anti-TF, in an inhomogeneous manner in terms of intensity and number of positive cells. There was a tendency for more positive and intensely stained cells to be found in well-differentiated structures such as tubules. Invasive ductal carcinomas exhibiting more positive and more strongly stained cells were less commonly metastatic to lymph nodes when compared with the tumours with no detectable or very low TF immunostaining. A semi-quantitatively recorded score of TF immunostaining correlated with the procoagulatory activity measured (7 fibroadenomas and 24 carcinomas). The results of this study suggest that proliferation and differentiation of the mammary gland is associated with enhanced TF expression in the epithelia which are negative for TF staining in the resting gland. Malignant growth is characterized by randomly expressed epithelial TF, which expression is enhanced and more frequent in well-differentiated tumour cells.