title: Clinical significance of folate receptor β-expressing tumor-associated macrophages in pancreatic cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Digestive Surgery, Kagoshima University, Kagoshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurahara
authors.forename: Sonshin
authors.initials: S
authors.lastname: Takao
authors.forename: Taisaku
authors.initials: T
authors.lastname: Kuwahata
authors.forename: Taku
authors.initials: T
authors.lastname: Nagai
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.forename: Koki
authors.initials: K
authors.lastname: Maeda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shinchi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mataki
authors.forename: Kosei
authors.initials: K
authors.lastname: Maemura
authors.forename: Takami
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Shoji
authors.initials: S
authors.lastname: Natsugoe
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D005260:Female; D005455:Fluorescent Antibody Technique; D058976:Folate Receptor 2 / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D058976:Folate Receptor 2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A