fibrin and Carcinoma--Intraductal--Noninfiltrating

The occurrence and distribution of components of coagulation pathways in situ 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 patients with benign breast tumors. Tumor cells stained for factor X and thrombomodulin but not for tissue factor, factor V, factor VII, or factor XIII. Rare nonneoplastic duct epithelial cells stained for thrombomodulin, but these tissues did not otherwise stain for any of these antigens. Macrophages within the tumor stroma stained for tissue factor, factor VII, and factor XIII but not for factor V or factor X. These features of macrophages were the same in malignant and nonmalignant breast tissue. Fibrinogen was present in abundance throughout the connective tissue in breast cancer but not in nonmalignant tissues. By contrast, no staining was observed using fibrin-specific antibodies. These results suggest that an intact coagulation pathway does not exist in breast cancer tissue and that thrombin capable of transforming fibrinogen to fibrin is not generated in significant amounts in this tumor type. While fibrin is not a feature of the connective tissue stroma in breast cancer, it is conceivable that the abundant fibrinogen present in the tumor connective tissue (and factor XIII present in connective tissue macrophages) might contribute to the structural integrity of breast tumor tissues.

Topics: Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Factor VII; Factor X; Fibrin; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; In Vitro Techniques; Thrombin; Transglutaminases

Study of 14 human infiltrating breast carcinomas revealed new features that shed light on the pathogenesis of tumor stroma formation and on host immunologic defense mechanisms. Fibrin deposits were observed in the stroma of all tumors, particularly at their growing edge. Fibrin may have contributed both to tumor angiogenesis and, with organization, to the formation of the fibrous stroma characteristic of these and other scirrhous carcinomas. We previously proposed similar mechanisms for several animal tumors. All breast carcinomas studied elicited some degree of lymphocytic response at the tumor periphery; lymphocytes penetrated the fibrous tumor stroma poorly, did not exit in significant numbers from central tumor vessels, and, even when greatly outnumbering tumor cells locally, appeared relatively ineffective at tumor cell killing. Microvascular endothelial cell damage was frequently observed and may have been responsible for zones of tumor infarction. Similar observations have been made in skin allografts and animal tumors where rejection was effected principally by microvascular damage and subsequent tissue infarction, not by lymphocyte contact with individual epithelial target cells.

Topics: Adenocarcinoma, Scirrhous; Adult; Aged; Animals; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Female; Fibrin; Fluorescent Antibody Technique; Guinea Pigs; Humans; Lymphocytes; Microscopy, Electron; Middle Aged; Venules

Topics: Adenofibroma; Basement Membrane; Breast; Breast Neoplasms; Carcinoma; Carcinoma, Intraductal, Noninfiltrating; Connective Tissue; Epithelium; Female; Fibrin; Fibroblasts; Humans; Microscopy, Electron