M2-polarized tumor-associated macrophage infiltration of regional lymph nodes is associated with nodal lymphangiogenesis and occult nodal involvement in pN0 pancreatic cancer

Pancreas. 2013 Jan;42(1):155-9. doi: 10.1097/MPA.0b013e318254f2d1.


Objective: Tumor-associated macrophages (TAMs) are reportedly involved in lymphangiogenesis in primary tumors, playing a crucial role in lymphatic metastasis. Furthermore, nodal lymphangiogenesis precedes and promotes regional lymph node (RLN) metastasis. We investigated the relationship of M2-polarized TAM infiltration of the RLNs, nodal lymphangiogenesis, and occult nodal involvement in pN0 pancreatic cancer.

Methods: Hematoxylin-eosin-stained primary tumor and regional LN specimens from 40 patients diagnosed with pN0 pancreatic cancer according to the pathological TNM classification were assessed. To evaluate lymphangiogenesis, lymphatic vessel density was measured by using D2-40 antibody. CD163 and cytokeratin AE1/AE3 antibodies were used to detect M2-polarized TAMs and isolated tumor cells in the RLNs, respectively.

Results: The nodal lymphatic vessel density had a strong association with the M2-polarized TAM density in the RLNs (P < 0.0001). Most of these TAMs expressed vascular endothelial growth factor C. Furthermore, in the RLNs, the M2-polarized TAM density was significantly associated with the incidence of isolated tumor cells (P = 0.0477).

Conclusions: M2-polarized TAM infiltration of RLNs is significantly associated with nodal lymphangiogenesis and occult nodal involvement in pN0 pancreatic cancer. Node-infiltrating M2-polarized TAMs may facilitate nodal lymphangiogenesis via the production of vascular endothelial growth factor C and thus promote RLN metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD / analysis
  • Antigens, Differentiation, Myelomonocytic / analysis
  • Biomarkers, Tumor / analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Keratins / analysis
  • Ki-67 Antigen / analysis
  • Lymph Nodes / chemistry
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology*
  • Lymph Nodes / surgery
  • Lymphangiogenesis*
  • Lymphatic Metastasis
  • Lymphatic Vessels / chemistry
  • Lymphatic Vessels / immunology
  • Lymphatic Vessels / pathology*
  • Macrophages / chemistry
  • Macrophages / immunology
  • Macrophages / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Pancreatic Neoplasms / chemistry
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / surgery
  • Receptors, Cell Surface / analysis
  • Staining and Labeling / methods
  • Vascular Endothelial Growth Factor C / analysis


  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers, Tumor
  • CD163 antigen
  • Ki-67 Antigen
  • Receptors, Cell Surface
  • VEGFC protein, human
  • Vascular Endothelial Growth Factor C
  • monoclonal antibody D2-40
  • Keratins