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. 2017 Apr 18;17(1):280.
doi: 10.1186/s12885-017-3259-8.

Prognostic significance of TRAIL-R3 and CCR-2 expression in tumor epithelial cells of patients with early breast cancer

Vivian Labovsky  1 , Leandro Marcelo Martinez  2 , Kevin Mauro Davies  3 , María de Luján Calcagno  4 , Hernán García-Rivello  3 , Alejandra Wernicke  3 , Leonardo Feldman  5 , Ayelén Matas  2 , María Belén Giorello  2 , Francisco Raúl Borzone  2 , Hosoon Choi  6 , Scott C Howard  7 , Norma Alejandra Chasseing  8
Affiliations

Prognostic significance of TRAIL-R3 and CCR-2 expression in tumor epithelial cells of patients with early breast cancer

Vivian Labovsky et al. BMC Cancer. .

Abstract

Background: Tumor epithelial cells (TEpCs) and spindle-shaped stromal cells, not associated with the vasculature, of patients with early breast cancer express osteoprotegerin (OPG), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), receptor activator of nuclear factor kappa B ligand, stromal cell derived factor-1, interleukin-6, macrophage colony stimulating factor, chemokine (C-C motif) ligand-2 (CCL-2) and their receptors at significantly higher levels compared with non-neoplastic breast tissues. We evaluated the clinicopathological significance of these ligands and receptors in TEpC and spindle-shaped stromal cells, not associated with the vasculature, to determine their impact on prognosis of patients with early-stage breast cancer.

Methods: We conducted immunohistochemical analyses of protein expression in primary tumors of patients with early breast cancer and analyzed their association with standard prognostic parameters and clinical outcomes, including local relapse, metastatic recurrence, disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS).

Results: Elevated levels of TRAIL-R3 and chemokine (C-C motif) receptor 2 (CCR-2) in TEpCs and OPG and CCL-2 in stromal cells were significantly associated with a higher risk of metastasis (p = 0.032, p = 0.003, p = 0.038, and p = 0.049; respectively). Moreover, high expression of TRAIL-R3 and CCR-2 in TEpCs was associated with shorter DFS, MFS, and OS. High TRAIL-R3 expression in TEpCs was an independent prognostic factor for DFS and OS, and high CCR-2 expression in these cells was an independent prognostic factor for MFS.

Conclusions: High levels of TRAIL-R3 and CCR-2 expression in TEpCs identified patients with early breast cancer with poor outcomes.

Keywords: CCR-2; Early breast cancer; Spindle-shaped stromal cells; TRAIL-R3; Tumor epithelial cells.

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Figures

Fig. 1
Fig. 1
Heat map of the association of ligand and receptor expression in TEpCs and spindle-shaped stromal cells with metastasis. Graphic show data for tumor samples with high and negative/low expression of ligand and receptor
Fig. 2
Fig. 2
Association of TRAIL-R3 expression in TEpCs with DFS, MFS, and OS. Kaplan–Meier curves show representative data for tumor samples with high and negative/low expression of TRAIL-R3 in TEpCs. Original magnification: 400×. Scale bars =50 μm
Fig. 3
Fig. 3
Association of CCR-2 expression in TEpCs with DFS, MFS, and OS. Images show representative data of tumor samples with high and negative/low expression of CCR-2 in TEpCs. Original magnification: 400×. Scale bars =50 μm
See this image and copyright information in PMC

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