Definition of antigenic heterogeneity and modulation among human mammary carcinoma cell populations using monoclonal antibodies to tumor-associated antigens.

Murine monoclonal antibodies, prepared against human metastatic mammary tumor cells, were used to demonstrate differential expression of several tumor-associated antigens (TAAs) among various mammary carcinomas and within a given tumor mass. Using the immunoperoxidase technique on serial sections of 39 human primary mammary carcinomas, a spectrum of antigenic phenotypes of TAAs was observed: 13% of the tumors reacted with all of a panel of four monoclonal antibodies; while 10% of the mammary tumors scored negative with all four antibodies. The remaining 30 tumors could be divided into several additional groups based on their differential reactivity with some, but not all, of the monoclonal antibodies. Furthermore, variation among mammary carcinomas was also observed in the cellular localization of antigens. Antigenic phenotypic diversity of mammary tumor cell populations within a given tumor mass was also observed; this was noted with respect to (a) antigenic expression in one area of a tumor mass and not another and (b) a "patchwork" effect in which antigens were expressed on cells immediately adjacent to cells which scored negative. Antigenic phenotypic diversity was also observed in established mammary tumor cell lines grown in vitro. A differential loss of some cell surface TAAs was observed as a function of continued cell passage; consistent with this finding, MCF-7 mammary tumor cell lines obtained from four sources could be differentiated from each other by their pattern of cell surface TAA expression. Single-cell clones derived from the MCF-7 mammary tumor cell line exhibited at least four distinct antigenic phenotypes; a change in cell surface phenotype of some of the clones was seen during subsequent passage. This definition of phenotypic variation and modulation of TAA expression among, and within, human mammary carcinomas has implications towards both the design and the outcome of studies involving the in situ immunodetection and therapy of breast cancer.