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Cellular Events Accompanying Regression of Skin Recurrences of Breast Carcinomas Treated with Intralesional Injections of Natural Interferons and ¹

The Arthur Purdy Stout Laboratory of Surgical Pathology [L. O.] and the Department of Surgery [D. V. H., C. M. D.], Columbia University, New York, New York 10032, and the National Public Health Institute, 00300 Helsinki, Finland [K. C.]

Cutaneous recurrences of breast carcinomas were treated with 10 i.l. injections of nIFNs and delivered in combination (7 lesions) or singly (11 with nIFN-, one with nIFN-). Histologically confirmed complete regressions occurred in 5 of 7 lesions treated with nIFN-/nIFN- and in 5 of 11 recurrences injected with nIFN- alone. In all cases specimens were obtained before and after therapy. In addition, in some cases (4 treated with nIFN-/nIFN-, 2 with nIFN-, one with nIFN-) multiple recurrences were injected simultaneously and were excised 24 h after 1, 3, and 10 injections and 21 days after completion of therapy. The main findings observed in the treated lesions undergoing complete and partial regressions included: (a) inhibition of mitotic activity and up-regulation of antigenic expression (mammary epithelial membrane antigen, intercellular adhesion molecule 1, HLA-DR) by the carcinoma cells; (b) activation of macrophages and dendrocytes with marked expression of HLA-DR and HLA-A,B,C; (c) infiltration of the dermis and tumors by activated T-lymphocytes (CD3⁺, CD4⁺, CD8⁺); (d) questionable participation by B-lymphocytes and natural killer cells; (e) activation of endothelium with enhancement of antigenic expression (intercellular adhesion molecule 1, HLA-DR), procoagulant activity, and vascular permeability. The responses elicited by nIFN-/nIFN- were greater than those caused by either IFN used alone. It appears that in these patients the IFNs exerted an antiproliferative action and potentiated a cell-mediated immunological response liminally present in the neoplastic tissues prior to therapy.

¹ Partial support was received from a Columbia University Research in Surgery Gift, the William J. and Mary F. Cooper Research Fund, the Margaret Milliken Hatch Foundation, the Milstein Family Foundation, the Ambrose Monell Foundation, Mrs. Mary K. Monell, Mr. and Mrs. George M. Shapiro, the Theodore and Renee Weiler Foundation, and the Weissman Charitable and Educational Fund.

² To whom requests for reprints should be addressed, at Division of Surgical Pathology, VC 14-206, Columbia Presbyterian Medical Center, 630 West 168 St., New York, NY 10032.

Received 12/ 4/91. Accepted 6/22/92.