title: Prognostic impact of CD204-positive macrophages in lung squamous cell carcinoma: possible contribution of Cd204-positive macrophages to the tumor-promoting microenvironment.
abstract: BACKGROUND
  Tumor-associated macrophages (TAMs) are recruited into cancer-induced stroma and produce a specific microenvironment for cancer progression. CD204 (+) TAMs are reportedly related to tumor progression and clinical outcome in some tumors. The aim of this study was to clarify the correlation between CD204 (+) TAMs and the clinicopathological features of lung squamous cell carcinoma.
  
  
  METHODS
  We investigated the relationships between the numbers of CD204 (+) TAMs and clinicopathological factors, microvessel density, and the numbers of Foxp3 (+) lymphocytes in 208 consecutively resected cases. We also examined the relationships between the numbers of CD204 (+) TAMs and the expression levels of cytokines involved in the migration and differentiation of CD204 (+) TAMs.
  
  
  RESULTS
  A high number of CD204 (+) TAMs in the stroma was significantly correlated with an advanced p-stage, T factor, N factor, and the presence of vascular and pleural invasion. A high number of CD204 (+) TAMs in the stroma was also a significant prognostic factor for all p-stages and p-stage I. Moreover, the numbers of CD204 (+) TAMs were correlated with the microvessel density and the numbers of Foxp3 (+) lymphocytes. A high number of CD204 (+) TAMs was strongly correlated with the tissue expression level of monocyte chemoattractant protein-1. CD204 (+) TAMs were shown to be significant independent prognostic factors in a multivariate analysis.
  
  
  CONCLUSIONS
  CD204 (+) TAMs were an independent prognostic factor in lung squamous cell carcinoma. CD204 (+) TAMs, along with other tumor-promoting stromal cells such as regulatory T cells and endothelial cells, may create tumor-promoting microenvironments.
authors.affiliation: Department of Pathology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; Department of Thoracic Oncology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Shunki
authors.initials: S
authors.lastname: Hirayama
authors.affiliation: Department of Pathology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. Electronic address: gishii@east.ncc.go.jp.
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.affiliation: Department of Thoracic Oncology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Nagai
authors.affiliation: Department of Pathology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan; Department of Thoracic Oncology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Ono
authors.affiliation: Department of Pathology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kojima
authors.affiliation: Department of Pathology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Chisako
authors.initials: C
authors.lastname: Yamauchi
authors.affiliation: Department of Thoracic Oncology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Keiju
authors.initials: K
authors.lastname: Aokage
authors.affiliation: Department of Thoracic Oncology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hishida
authors.affiliation: Department of Thoracic Oncology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Yoshida
authors.affiliation: Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Pathology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. Electronic address: aochiai@east.ncc.go.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008207:Lymphatic Metastasis; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C495139:MSR1 protein, human; D012333:RNA, Messenger; D051117:Scavenger Receptors, Class A