[Human mammary carcinoma. A model for the relationship between tumor proliferation, tumor-associate macrophages, and prognostic factors]

Abstract

As compared with the lymphatic system, the mononuclear phagocyte system (MPS) represents the older defense system in the course of evolution. Organisms with defective or with no lymphocytic function are able to live for a certain time while metazoa cannot develop and exist without cells capable of phagocytosis. It is known that up to 80% of the mass of malignant experimental tumors may consist of macrophages. The biological relevance of these tumor-associated macrophages (TAM), however, is contested to date. Besides well-known tasks in specific and non-specific defense, the cells of the MPS possess nutritive functions. The different functions of TAM have been essentially examined in animal experiments in vivo and in vitro up to now. These studies have shown, e.g., that TAM of different phenotypes to some extent are assigned to different functions and that each tumor or tumor cell line has a specific TAM pattern. The available number of monoclonal antibodies (MAB) able to recognize different groups of human macrophages has only increased in the recent past. This also provided evidence of the phenotypic heterogeneity of macrophages in the human system. On the other hand, there is little knowledge to date of the possible biological cause of the presence of numerous macrophages also in the stroma of malignant tumors in man and on the functional relevance of particular macrophage phenotypes. In the present studies, the phenotypic pattern of tumor-associated cells was examined by immunohistochemistry in the model of human mammary carcinoma, using 18 monoclonal antibodies (Ki-M1-8, Leu-M1-3, Leu-M5, EBM11, CD1, anti-transferrin receptor [TFR], anti-MHC I, anti-MHC II or anti HLA-DR) and one polyclonal antibody (anti protein-S100). The first part of the study contains a semiquantitative evaluation of 216 cases of mammary carcinoma. The analytical results are correlated with established prognostic factors available in the case of malignant tumors in general and in that of mammary carcinomas in particular (age, menopausal status of patients, axillary lymph node and estrogen/progesterone receptor status, size of tumor, tumor type according to WHO, degree of malignancy according to histopathological and nuclear grading). As tumor parameters of absolute biological relevance, proliferating activity (Ki67) and MHC phenotype of tumor cells and amount or types of tumor-associated lymphocytes (TAL) are examined in order to analyze their correlation with prognostic factors and their importance in the tumor-macrophage system.(ABSTRACT TRUNCATED AT 400 WORDS)