Detection of M2 macrophages and colony-stimulating factor 1 expression in serous and mucinous ovarian epithelial tumors

Pathol Int. 2009 May;59(5):300-5. doi: 10.1111/j.1440-1827.2009.02369.x.


Tumor-associated macrophages (TAM) are known to possess the immunosuppressive M2 macrophage phenotype. They contribute to tumor growth, invasion, and metastasis by producing various mediators. Macrophages, especially M2 polarized macrophages, preferentially express CD163 and CD204, but few studies have investigated macrophage phenotypes in human ovarian tumors. The purpose of the present study was therefore to present results on macrophage differentiation in human ovarian serous and mucinous epithelial tumors. The method focused on immunostaining of paraffin-embedded tumor samples. Almost all macrophages infiltrating tumor tissues expressed CD163 and CD204, indicating the phenotypic shift toward M2 macrophage. The numbers of CD68-positive macrophages as well as of CD163- and CD204-positive macrophages in borderline and malignant tumors were significantly higher than in benign tumors. They correlated well with histological gradient of malignancy. Macrophage colony-stimulating factor (also known as colony-stimulating factor; CSF-1), which is one of the cytokines considered to induce TAM to polarize toward an M2 phenotype, was then evaluated. CSF-1 expression in malignant tumor cells was significantly higher than that in benign tumor cells and correlated with histological malignancy. These results suggest that CSF-1 derived from tumor tissues induces macrophages to shift toward the M2 phenotype, which is considered to promote tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Cell Differentiation / immunology
  • Cystadenocarcinoma, Mucinous / immunology*
  • Cystadenocarcinoma, Mucinous / pathology
  • Cystadenocarcinoma, Serous / immunology*
  • Cystadenocarcinoma, Serous / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Macrophage Colony-Stimulating Factor / biosynthesis*
  • Macrophages / cytology
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Middle Aged
  • Neoplasm Invasiveness / immunology
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / pathology
  • Phenotype
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism
  • Scavenger Receptors, Class A / immunology
  • Scavenger Receptors, Class A / metabolism


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • MSR1 protein, human
  • Receptors, Cell Surface
  • Scavenger Receptors, Class A
  • Macrophage Colony-Stimulating Factor