Prognostic significance of TRAIL-R3 and CCR-2 expression in tumor epithelial cells of patients with early breast cancer
Vivian Labovsky,
Leandro Marcelo Martinez,
Kevin Mauro Davies,
María de Luján Calcagno,
Hernán García-Rivello,
Alejandra Wernicke,
Leonardo Feldman,
Ayelén Matas,
María Belén Giorello,
Francisco Raúl Borzone,
Hosoon Choi,
Scott C. Howard,
Norma Alejandra Chasseing
Affiliations
Vivian Labovsky
Instituto de Biología y Medicina Experimental, Laboratorio de Inmunohematología (IBYME) – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
Leandro Marcelo Martinez
Instituto de Biología y Medicina Experimental, Laboratorio de Inmunohematología (IBYME) – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
Kevin Mauro Davies
Departamento de Anatomía Patológica, Hospital Italiano
María de Luján Calcagno
Departamento de Bioestadística, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires
Hernán García-Rivello
Departamento de Anatomía Patológica, Hospital Italiano
Alejandra Wernicke
Departamento de Anatomía Patológica, Hospital Italiano
Leonardo Feldman
Departamento de Trasplante de Medula Ósea, Fundación Favaloro
Ayelén Matas
Instituto de Biología y Medicina Experimental, Laboratorio de Inmunohematología (IBYME) – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
María Belén Giorello
Instituto de Biología y Medicina Experimental, Laboratorio de Inmunohematología (IBYME) – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
Francisco Raúl Borzone
Instituto de Biología y Medicina Experimental, Laboratorio de Inmunohematología (IBYME) – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
Hosoon Choi
Central Texas Veterans Research Foundation
Scott C. Howard
University of Tennsseee Health Sciences Center
Norma Alejandra Chasseing
Instituto de Biología y Medicina Experimental, Laboratorio de Inmunohematología (IBYME) – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
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.
