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Occurrence of Components of Fibrinolysis Pathways in Situ in Neoplastic and Nonneoplastic Human Breast Tissue¹

Departments of Medicine [V. C., L. R. Z.] and Pathology [V. A. M.], Dartmouth Medical School, Hanover, New Hampshire and the Veterans Administration Medical Center, White River Junction, Vermont 05001 [V. C., L. R. Z., S. M. R.]; Plasma Protein-Coagulation Laboratory, New York Blood Center, New York, New York 10021 [B. J. K.]; and Departments of Medicine and Biochemistry, University of Vermont Medical School, Burlington, Vermont 05405 [D. C. S.]

The occurrence and distribution of components of fibrinolysis pathways were determined using immunohistochemical techniques applied to 10 cases of primary carcinoma of the breast, normal breast tissue obtained from two patients undergoing reductive mammoplasty, and three cases of benign breast tumors. Tumor cells stained for urokinase- and tissue-type plasminogen activators, plasminogen activation inhibitor-1, plasminogen, and plasmin-antiplasmin complex neoantigen. The tumor connective tissue stained for fibrinogen and its D fragment plasmin digestion product. By contrast, only occasional nonneoplastic duct epithelial cells stained for urokinase- and tissue-type plasminogen activators and there was little or no staining for the other antigens tested. These results are consistent with the existence of local amplification of expression of enzymatically active plasminogen activators, and particularly of urokinase-type plasminogen activator, in situ in primary breast cancer tissue. These features distinguish malignant from benign breast tissue and may modulate neoplastic progression through an effect on tumor cell proliferation, invasion, and metastatic dissemination.

¹ Supported in part by the Department of Veterans Affairs Medical Research Service and research grants from the National Institutes of Health HL21465 (B. J. K.), HL35058 (D. C. S.), and BRSG S07RR05392 (L. R. Z.).

² V. C. is a Visiting Scientist, Dartmouth Medical School, and recipient of a Fellowship from the Italian National Research Council-NATO. Permanent address: Istituto di Semeiotica Medica, Università di Perugia, Via E. dal Pozzo, 06100 Perugia, Italy.

³ To whom requests for reprints should be addressed, at the VA Medical and Regional Office Center, White River Junction, VT 05001.

Received 1/16/90. Accepted 9/24/90.

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