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

GIORELLO MB; DAVIES KM; WERNICKE A; CHASSEING NA; BORZONE FR,; CALCAGNO ML; MATAS A; MARTINEZ LM; GARCIA-RIVELLO H; LABOVSKY V

Mar del Plata

Congreso; Reunión Anual Conjunta Sociedad Argentina de Investigación Clínica (SAIC, LXI Reunión Anual), la Sociedad Argentina de Inmunología (SAI, LXIV Reunión Anual) y la Sociedad Argentina de Farmacología Experimental (SAFE, XLVIII Reunión Anual); 2016

SAI, SAIC, SAFE

Medicina (Bs.As.) 2016, vol 76 sup 1: abst 126, pg 129. Abstract: Despite improvements in technology and early diagnosis, many patients still succumb to the disease if the primary breast tumor metastasizes to secondary organs. Thereby, detection of new prognostic and predictive factors in breast cancer that could provide a target for new therapeutic treatments as well as to define prognosis is being sought worldwide.In previous work, we found that tumor epithelial cells (TEpCs) and spindle-shaped stromal cells (SCs), not associated with the vasculature, of early breast cancer patients (BCP) expressed OPG, TRAIL, RANKL, SDF-1, IL-6, M-CSF, CCL-2 and their receptors at significantly higher levels compared with non-neoplastic breast tissues. Therefore, our aim was to explore the clinicopathological significance of these ligands and receptors for TEpCs and SCs, as prognostic determinants of early BCP. We conducted immunohistochemical analysis of these proteins expression in TEpC and SCs of invasive ductal primary tumors with early BCP, and analyzed their association with clinicopathological characteristics, including local relapse, metastatic recurrence, disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS).We found that elevated levels of TRAIL-R3 and CCR-2 (CCL-2-R) in TEpCs and OPG and CCL-2 in these SCs were 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. Finally, 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. This study is the first to demonstrate that high levels of TRAIL-R3 and CCR-2 expression in TEpCs identified patients with early breast cancer with poor outcomes.