Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C-C chemokines.

Abstract

We have defined the host leukocyte infiltrate in epithelial ovarian tumors and related this to the expression of C-C chemokines. Immunohistochemical analysis of 20 paraffin-embedded biopsies showed that the infiltrate was primarily composed of CD68+ macrophages and CD8+/CD45RO+ T cells (median values, 3700 cells/mm3 and 2200 cells/mm3, respectively). Natural killer cells, B cells, and mast cells occurred in lower numbers (median values, 0 to 200 cells/mm3). Eosinophils were rarely seen and neutrophils were mainly confined to blood vessels. More infiltrating cells were found in stromal than in tumor areas. Only macrophages occurred in significant numbers in areas of necrosis (P < 0.0005). Using in situ hybridization to mRNA, we examined expression of the chemokines MCP-1, MIP-1 alpha, MIP-1 beta, and RANTES. MCP-1 and MIP-1 alpha were expressed by significantly more cells than MIP-1 beta and RANTES (P < 0.005). In tumor epithelial areas, the predominant chemokine was MCP-1. MCP-1 and MIP-1 alpha were the predominant stromal chemokines. A significant correlation was found between the total number of CD8+ T cells and the number of cells expressing MCP-1 (rs = 0.63 and P < 0.003, respectively) and between the CD8+ population and RANTES-expressing cells (rs = 0.6 and P < 0.003). A correlation was also found between CD68+ macrophages and the number of cells expressing MCP-1 (rs = 0.50 and P = 0.026). We suggest that MCP-1 may be responsible for the leukocyte infiltrate in ovarian carcinomas, but the expression of other chemokines may determine its exact nature.