CD68, CD163, and matrix metalloproteinase 9 (MMP-9) co-localization in breast tumor microenvironment predicts survival differently in ER-positive and -negative cancers

• DOI: 10.1186/s13058-018-1076-x
• Publication Date: 2018-12-17T12:23:03Z
• Authors: Vasiliki Pelekanou; Franz Villarroel-...; Kurt A. Schalper; Lajos Pusztai; David L. Rimm
• Keywords: Tissue microarray; CD163; CD68; Triple-negative breast cancer

The role of tumor-associated macrophages (TAMs) in the cancer immune landscape and their potential as treatment targets or modulators response to are gaining increasing interest. TAMs display high molecular functional complexity. Therefore objective assessment breast biomarkers is critical. aims this study were objectively determine situ expression significance TAM (CD68, CD163, MMP-9) identify subclasses patients who could benefit from TAM-targeting therapies. We measured CD68, MMP-9 protein formalin-fixed paraffin-embedded tissues carcinomas represented tissue microarray format using multiplexed quantitative immunofluorescence (QIF) two independent Yale cohorts: cohort A—n = 398, estrogen receptor–positive (ER+) ER− cases—and triple-negative (TNBC)-only B (n 160). Associations between macrophage markers, ER status, survival assessed. Protein by QIF was compared with mRNA data METABRIC study. All three markers co-expressed, displaying higher cancers. High pan-macrophage marker CD68 correlated poorer overall (OS) only cases A (P 0.02). CD163 associated improved OS (cohort A, P 0.03 TNBC B, 0.04, respectively) but not ER+ individually OS. CD68+/CD163+ worse tumors <0.001) In dataset, levels followed co-expression pattern observed did always show same trend regarding Macrophage activity correlate differently association co-localization MMP-9/CD163/CD68 poor cancers suggests that these may be candidates for macrophage-targeted