title: Type 2 Endometrial Cancer is Associated With a High Density of Tumor-Associated Macrophages in the Stromal Compartment.
abstract: BACKGROUND
  Tumor-associated macrophages (TAMs) play a pivotal role in orchestrating the microenvironment. The TAMs differentially polarize into M1 or M2 macrophages with distinct actions. The aim of our work is to characterize density, subtype, and location of TAMs in endometrial hyperplasia and cancer.
  
  
  METHODS
  Formalin-fixed, paraffin-embedded sections of hyperplasia (n = 5), type 1 (n = 5), and type 2 (n = 5) endometrial cancer were stained with anti-CD68 and anti-CD163 monoclonal antibodies as markers for total TAMs and M2 TAMs, respectively. Macrophages were counted at 40× magnification in 10 high-power fields (HPFs) per slide by 4 observers. Repeated measures models were constructed to determine the relationships between macrophages and lesion categories.
  
  
  RESULTS
  Most CD68+ TAMs were located in the stromal (mean = 41.0/HPF) compared to epithelial (mean = 11.0/HPF) or luminal (mean = 11.6/HPF) compartments. Similar but reduced findings were observed for CD163+ (M2 subtype) TAMs. The CD68+ stromal TAM density was highest in patients with type 2 cancers (mean = 54.0/HPF) compared to those with type 1 cancers (mean = 35.5/HPF) and hyperplasia (mean = 29.0/HPF). Women with hyperplasia had more CD163+ (M2 subtype) TAMs (26.7/HPF) than patients with either type of cancer (type 1 = 12.5/HPF and type 2 = 11.5/HPF). Based on the repeated measures models, type 2 cancers had 38.6/HPF more CD68+ TAMs than type 1 cancers (P < .0001) and type 1 and type 2 cancers had similar numbers of CD163+ TAMs (P = .27).
  
  
  CONCLUSIONS
  Type 2 cancers have nearly twice the TAM density of type 1 cancers. This difference may be due to M1 macrophage predominance in the stroma of type 2 cancers.
authors.affiliation: Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC, USA mgkelly@wakehealth.edu.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kelly
authors.affiliation: Faculdade de Ciências da Saúde "Dr. José Antônio Garcia Coutinho", Universidade do Vale do Sapucaí, Pouso Alegre, Brazil.
authors.forename: Antonio M C
authors.initials: AM
authors.lastname: Francisco
authors.affiliation: Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Adela
authors.initials: A
authors.lastname: Cimic
authors.affiliation: Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Wofford
authors.affiliation: Department of Statistics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Nora C
authors.initials: NC
authors.lastname: Fitzgerald
authors.affiliation: Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Taylor
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D002452:Cell Count; D004714:Endometrial Hyperplasia / Q000276:immunology / Q000473:pathology*; D016889:Endometrial Neoplasms / Q000145:classification / Q000276:immunology / Q000473:pathology*; D004717:Endometrium / Q000276:immunology / Q000473:pathology*; D005260:Female; D005404:Fixatives; D005557:Formaldehyde; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008875:Middle Aged; D015588:Observer Variation; D016612:Paraffin Embedding; D010641:Phenotype; D011237:Predictive Value of Tests; D011956:Receptors, Cell Surface / Q000032:analysis; D015203:Reproducibility of Results; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology*; D016707:Tissue Fixation / Q000379:methods; D059016:Tumor Microenvironment; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D051940:B7-2 Antigen; D014408:Biomarkers, Tumor; D005404:Fixatives; D005557:Formaldehyde; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C497964:CD86 protein, human
keywords: endometrial cancer; tumor microenvironment; tumor-associated macrophages