Markers of breast cancer development expressed by epithelial tumor and stromal cells: future perspectives.

LABOVSKY V; MARTINEZ LM; CALCAGNO ML; DAVIES KM; WERNICKE A; GARCIA-RIVELLO H; FERNANDEZ VALLONE VB; CHASSEING NA

Miami

Conferencia; 13th International Conference on Cancer-Induced Bone Disease (CIBD) - International Bone and Mineral Society (IBMS).; 2013

International Bone and Mineral Society (IBMS).

IBMS BoneKEy, abstract P074, page S50, 2013. doi: 10.1038/bonekey.2013.151. ABSTRACT: Despite advance in the study of breast cancer (BC) progression mechanisms and novel therapeutic treatment development, it remains as the second leading cause of mortality among women. Classical diagnostic factors are not enough to prevent BC patients (BCP) from developing metastasis. The aim of this work was to study non-classical markers´ expression [OPG, TRAIL, TRAIL receptors (R) (R1-4), RANKL, RANK, SDF-1, CXCR-4, IL-6, IL-6-R, M-CSF and M-CSF-R] in tumor epithelial (TEpC) and stromal (SC) cells, evaluating the possible association between these parameters and the classical ones (age, ER, PR, HER2, tumor size and histological grade). This was a prospective cohort study including 20 primary tumor biopsy (infiltrative ductal carcinoma, I-II stage BCP) and 10 non-neoplastic breast tissues (control). Evaluation of the % of positive cells was done by immunohistochemistry. Clinicopathological data was retrieved from pathology and medical records. Mann-Whitney test and Spearman´s rank correlation coefficient were used (p= or less than 0.05). TRAIL-R2, -R3, -R4, RANK, RANKL, OPG, IL-6, IL-6R, CXCR4 showed significant higher expression in TEpC and BCP-SC than controls (p=0.05). Expression of SDF-1 and MCSF was significant higher in TEpC than control (p=0.0286; 0.0321). In BCP, the % of TRAIL, OPG and SDF-1 expression in TEpC was higher than BCP-SC (p=0.0001). In TEpC, TRAIL-R1 and -R4 expression was associated with TRAIL expression in them; IL-6R, CXCR4 and SDF-1 expression in TEpC was associated with IL-6, SDF-1 and CXCR4 in BCP-SC (p=0.0236; 0.0009; 0.0413). In BCP, the % of SC expressing TRAIL, IL-6 and SDF-1 was associated with TRAIL-R3, IL-6R and CXCR4 expression in them (p=0.038; 0.016; 0.0009). The % of TRAIL and RANKL expression in control-SC was associated with TRAIL-R3, -R4 and RANK expression in them (p=0.0266; 0.0152; 0.0039). In these TEpC TRAIL-R1, -R3 and OPG expression was associated with age (p=0.0407; 0.0147; 0.0361); RANKL and OPG expression was associated with HER2 (p=0.0206 inversely; 0.008); TRAIL-R2 and OPG expression was inversely associated with histological grade (p=0.0088; 0.0363). OPG and M-CSF-R expression was associated with desmoplasia (p=0.0009 inversely; 0.0008). These data showed the importance of evaluating the non-classical parameters in TEpC and in BCP-SC. These results could be useful in identifying patients with more aggressive tumors at risk of bone metastasis, which may thus improve the available options for therapeutic intervention.