The Clinical Significance of CD169-Positive Lymph Node Macrophage in Patients with Breast Cancer

PLoS One. 2016 Nov 18;11(11):e0166680. doi: 10.1371/journal.pone.0166680. eCollection 2016.

Abstract

The immune status of patients can impact on the clinical course of cancer. Lymph node (LN) macrophages play critical roles in anti-cancer immunity via the activation of cytotoxic T-lymphocytes (CTLs). In this study, the prognostic significance of CD169+ LN macrophages was examined in patients with breast cancer. For this purpose the number of CD169+ cells and their ratio relative to total macrophages (CD68+) in regional LNs (RLNs), as well as the number of CD8+ CTLs in tumor tissues, were investigated using immunohistochemistry of paraffin-embedded tissue samples from 146 patients with breast cancer. The association of these data with clinicopathological factors was then analyzed. The number of cells positive for the pan-macrophage marker CD68 remained relatively uniform, while the number of CD169+ cells varied across all cases. Moreover, a high density of CD169+ cells correlated with early clinical stage and no LN metastasis, while a higher CD169+ to CD68+ ratio was significantly associated with small tumor size and a low Ki-67+ rate. There was also a significant correlation between the number of CD8+ CTLs and that of CD169+ macrophages in high grade breast cancer cases with a Ki-67 index greater than 40%. However, neither the density nor the ratio of CD169+ cells, nor the density of CD8+ CTLs, were associated with relapse-free survival, distant relapse-free survival, or breast cancer-specific survival. These findings suggest that CD169+ macrophages in RLNs might be a useful marker for assessing clinical stage, including LN states, in patients with breast cancer.

MeSH terms

  • Adult
  • Biomarkers
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Lymph Nodes / metabolism*
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Sialic Acid Binding Ig-like Lectin 1 / metabolism*
  • Survival Analysis
  • Tumor Burden
  • Young Adult

Substances

  • Biomarkers
  • Sialic Acid Binding Ig-like Lectin 1

Grants and funding

This study was supported in part by Grants-in-Aid for Scientific Research (26460454) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.