Macrophage density and macrophage colony-stimulating factor expression predict the postoperative prognosis in patients with intrahepatic cholangiocarcinoma.

Abstract

Macrophages are included in the stromal compartments in various neoplasms, and their behavior against tumors is diverse. The aim of this study was to examine the role of tumor-infiltrating macrophages and their main regulator, macrophage colony-stimulating factor (M-CSF), in intrahepatic cholangiocarcinoma (ICC). Macrophage density and M-CSF expression in 39 resected ICC specimens were immunohistochemically evaluated in the central and peripheral areas of tumors, which were defined as fields more than and within 500 μm from the invasive front, respectively. The number of CD68-positive macrophages was counted using an image-analyzing software program. The relationship between these results and other clinicopathological factors and the postoperative prognosis were evaluated. Sporadic M-CSF expression in cancer cells around the peripheral area was observed in fourteen patients. M-CSF-positive ICCs showed a higher macrophage density in the tumor-peripheral area than did M-CSF-negative ICCs. M-CSF expression and higher macrophage density in the tumor-peripheral area were related to a better postoperative prognosis, whereas a higher macrophage density in the central area was one of the significant risk factors for a poor prognosis in a univariate analysis. Tumor-peripheral macrophage infiltration, presumably dependent on M-CSF, and M-CSF-independent tumor-central macrophage infiltration are predictive factors for better and worse postoperative prognosis in ICC patients, respectively. The tumor microenvironment, such as the presence of hypoxia, may affect the behavior of infiltrating macrophages in ICC.