We have obtained cell-type specific antibodies both monoclonal and polyclonal against normal surface antigens of human mammary eptihelial cells (anti-HME), that bind specifically to normal human mammary epithelial cell surface antigens (HME-Ags) and, with different intensities and at varying percentages, to epithelial cells of fibroadenomas and breast carcinomas, and to human neoplastic mammary cell lines. These antigens could participate in cellular functions such as adhesiveness, arrangement and communication and could control cell multiplication and metastatic capabilities. Loss or substitution of these normal HME cell antigens (differentiation antigens) could be concomitant with, or perhaps the cause of, breast neoplasia. We have also quantitated by radioimmunoassy and flow cytofluorimetry levels of HME-Ags on a whole population na don a cell per cell basis. Mammary tumors had lower levels than normal breast tissue and were more heterogeneous. Con-A receptors were also found at a higher level in human breast cancer. These findings are being added to determinations of other non-spcific markers of HME-cells and are being assembled into a system for classification of mammary tumors. Experimental support for these investigations is given by a parallel system in the mouse. Studies are proposed in order to add new cell membrane markers to the ones in use now, to refine further our quantitative techniques, and to test a much larger number of breast tumors. Then breast tumors will be placed in clusters sharing comparable values of antigenic expression and phenotypic heterogeneity and compared to the clinical history of the patients. A classification of breast tumors using as its basis the molecular alterations that could condition breast neoplastic disease will be then attempted. This classification of breast tumors at the molecular level, will be matched to the tumor's clinical staging, histopathology, and evolution (response to chemo and radiation therapy, appearance of metastases, etc.), in order to derive elements to establish future guidelines in its therapy and prognosis.
