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

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.