Annals of Surgical Oncology

, Volume 19, Issue 7, pp 2264–2271 | Cite as

Clinical Significance of Folate Receptor β–expressing Tumor-associated Macrophages in Pancreatic Cancer

  • Hiroshi Kurahara
  • Sonshin TakaoEmail author
  • Taisaku Kuwahata
  • Taku Nagai
  • Qiang Ding
  • Koki Maeda
  • Hiroyuki Shinchi
  • Yuko Mataki
  • Kosei Maemura
  • Takami Matsuyama
  • Shoji Natsugoe
Pancreatic Tumors



To examine the appearance and distribution of folate receptor β-expressing (FRβ+) macrophages in the pancreatic tumor microenvironment and their relationship to metastasis and prognosis in pancreatic cancer patients.


Tumor samples were obtained from 76 patients with pancreatic cancer who underwent curative resection. None of these patients had received any preoperative chemotherapy or radiotherapy. Both FRβ+ and tumor-infiltrating (CD68+) macrophages were examined in each tumor specimen by immunohistochemical and immunofluorescence staining using a newly developed anti-human FRβ monoclonal antibody and CD68 antibody. The appearance, distribution, expression of vascular endothelial growth factor (VEGF) on FRβ-expressing or CD68+ macrophages, and tumor microvessel density (MVD) were assessed. Log rank test and Cox proportional hazard regression were used to investigate the associations among CD68+ or FRβ+ macrophages, clinicopathologic factors, and overall survival.


FRβ+ macrophages were prominent in the perivascular regions of the tumor-invasive front and a specific subset with VEGF expression in the CD68+ macrophages. A high number of FRβ+ macrophages showed a positive association with high MVD, a high incidence of hematogenous metastasis, and a poor prognosis in pancreatic cancer patients.


FRβ+ macrophages are a novel subset of tumor-associated macrophages in pancreatic cancer and may play an important role in the tumor microenvironment in association with systemic metastasis through the interaction with tumor cells and vessels. FRβ+ macrophages may be promising a targeting therapy for pancreatic cancer.


Vascular Endothelial Growth Factor Pancreatic Cancer Tumor Microenvironment Vascular Endothelial Growth Factor Expression Pancreatic Cancer Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, Ministry of Health, Labour, and Welfare, Japan.


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Copyright information

© Society of Surgical Oncology 2012

Authors and Affiliations

  • Hiroshi Kurahara
    • 1
  • Sonshin Takao
    • 2
    • 3
    Email author
  • Taisaku Kuwahata
    • 1
    • 3
  • Taku Nagai
    • 4
  • Qiang Ding
    • 3
  • Koki Maeda
    • 1
    • 3
  • Hiroyuki Shinchi
    • 5
  • Yuko Mataki
    • 1
  • Kosei Maemura
    • 1
  • Takami Matsuyama
    • 4
  • Shoji Natsugoe
    • 1
  1. 1.Department of Digestive SurgeryKagoshima UniversityKagoshimaJapan
  2. 2.Department of Cancer and Regenerative MedicineKagoshima UniversityKagoshimaJapan
  3. 3.Frontier Science Research CenterKagoshima UniversityKagoshimaJapan
  4. 4.Department of ImmunologyGraduate School of Medical Sciences, Kagoshima UniversityKagoshimaJapan
  5. 5.Department of Health SciencesKagoshima UniversityKagoshimaJapan

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