title: Prognostic significance of tumor-associated macrophages in endometrial adenocarcinoma.
abstract: OBJECTIVE
  Endometrial adenocarcinoma is one of the most common gynecologic malignancies worldwide and in stages confined to the uterus considered to have an excellent prognosis. However, in advanced or recurrent cases when surgery fails to achieve disease control other treatment options are less effective. Thus, new therapeutic avenues are needed.
  
  
  METHODS
  To provide the rationale for the use of novel agents that target immune checkpoints 163 type I endometrial cancer samples were immunohistochemically screened for the presence of CD163(+) tumor-associated macrophages and Foxp3(+) regulatory T cells. Further, a D2-40-based evaluation of lymph vessel density and lymphovascular space invasion was carried out. Correlation analysis with clinicopathological parameters was performed; Kaplan-Meier curves were generated; multivariate analysis was undertaken as appropriate.
  
  
  RESULTS
  A substantial amount of tumor-associated macrophages and regulatory T cells was detected in all specimens characterizing endometrial cancer as an immunogenic tumor. However, only the increased infiltration of tumor-associated macrophages was proportionally associated with advanced FIGO stages, high tumor grade, increased lymph vessel density, lymphovascular space invasion and lymph node metastasis. Thus, the presence of tumor-associated macrophages indicates aggressive tumor behavior and appeared to be an independent prognostic factor for recurrence-free survival.
  
  
  CONCLUSIONS
  Our results make future therapeutic approaches that target tumor-associated macrophages reasonable to improve the outcome of women with advanced or recurrent endometrial adenocarcinoma.
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany. Electronic address: Kirsten.Kuebler@ukb.uni-bonn.de.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Kübler
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Tiyasha H
authors.initials: TH
authors.lastname: Ayub
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Weber
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Zivanovic
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Alina
authors.initials: A
authors.lastname: Abramian
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Mignon-Denise
authors.initials: MD
authors.lastname: Keyver-Paik
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Mallmann
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Kaiser
authors.affiliation: Institute of Pathology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Nuran Bektas
authors.initials: NB
authors.lastname: Serçe
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Walther
authors.initials: W
authors.lastname: Kuhn
authors.affiliation: Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Rudlowski
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000276:immunology; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D011956:Receptors, Cell Surface
keywords: CD163; Endometrial adenocarcinoma; Lymph vessel density; Lymphovascular space invasion; Regulatory T cells; Tumor-associated macrophages