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Type 2 Endometrial Cancer is Associated With a High Density of Tumor-Associated Macrophages in the Stromal Compartment

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Abstract

Introduction

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.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, 27157, NC, Winston-Salem, USA

    Michael G. Kelly MD, Anne Wofford MS, Jie Yu MD & Robert N. Taylor MD, PhD

  2. Faculdade de Ciências da Saúde “Dr. José Antônio Garcia Coutinho”, Universidade do Vale do Sapucaí, Pouso Alegre, Brazil

    Antonio M. C. Francisco MD

  3. Department of Pathology, Wake Forest University School of Medicine, NC, Winston-Salem, USA

    Adela Cimic MD

  4. Department of Statistics, Wake Forest University School of Medicine, NC, Winston-Salem, USA

    Nora C. Fitzgerald MS

Authors
  1. Michael G. Kelly MD
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  2. Antonio M. C. Francisco MD
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  3. Adela Cimic MD
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  4. Anne Wofford MS
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  5. Nora C. Fitzgerald MS
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  6. Jie Yu MD
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  7. Robert N. Taylor MD, PhD
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Correspondence to Michael G. Kelly MD.

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Kelly, M.G., Francisco, A.M.C., Cimic, A. et al. Type 2 Endometrial Cancer is Associated With a High Density of Tumor-Associated Macrophages in the Stromal Compartment. Reprod. Sci. 22, 948–953 (2015). https://doi.org/10.1177/1933719115570912

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  • DOI: https://doi.org/10.1177/1933719115570912

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