Expression of acute and late-stage inflammatory antigens, c-fms, CSF-1, and human monocytic serine esterase 1, in tumor-associated macrophages of renal cell carcinomas

Purpose: Tumor cells influence the differentiation of infiltrating macrophages. In the present study, the differentiation of macrophages in renal cell carcinomas was investigated with special regard to their possible role in tumor growth and spread. Methods: Macrophages were characterized by means of immunohistochemistry of the Ki-M1P, 25F9, MRP8, MRP14, and MRP8/14 antigens and by means of in situ hybridization of CSF-1, its c-fms-coded corresponding receptor, and human monocytic serine esterase-1 (HMSE-1) mRNA. Macrophage subgroups were quantified within central tumor tissue, the corresponding tumor host interface, and tumor-free tissue and correlated with tumor necrosis, fibrosis, and tumor stage and grade. Results: Macrophage density was much higher within tumor tissue and the tumor/host interface than in tumor-free tissue. Well-differentiated carcinomas showed a lower degree of macrophage density than less-differentiated carcinomas. Tumor-associated macrophages could be divided into an active inflammatory type (MRP14⁺, MRP8/14⁺) and into a late-phase inflammatory type (25F9⁺, MRP8⁺). Necrosis was seen in less-differentiated carcinomas and associated with a significantly increased density of MRP14⁺ macrophages, which, however, did not correlate with the extent of necrosis. The density of 25F9⁺ macrophages was correlated with an extensive connective tissue formation and an advanced tumor stage. c-fms, CSF-1, and HMSE-1 mRNA expression did not discriminate between the macrophage subgroups. Conclusions: Tumor-associated macrophages of the late-stage inflammatory type potentially support the spread of renal cell cancer. CSF-1 derived from tumor cells and macrophages acts as a monocyte attractant and induces macrophage differentiation able to modulate the extracellular matrix rather than to exert cytotoxicity. Received: 25 May 2000 / Accepted: 29 June 2000