Rank receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer.

CALCAGNO ML; DAVIES KM; BORZONE FR; CHASSEING NA; WERNICKE A; MARENCO P; CHASSEING NA; MUNICOY J; WERNICKE A; MARENCO P; MUNICOY J; LABOVSKY V; GARCIA-RIVELLO H; MARTINEZ LM; GIORELLO MB; LABOVSKY V; GARCIA-RIVELLO H; MARTINEZ LM; GIORELLO MB; CALCAGNO ML; DAVIES KM; BORZONE FR

Congreso; Reunion conjunta de sociedades de biociencias; 2017

In breast carcinomas (BC), most stromal cells are fibroblasts, and 80% of them are tumor-associated fibroblasts (TAF), characterized by increased expression of α-SMA and FSP, among others markers. One source of TAF is bone marrow (BM)-mesenchymal stem cells (MSC) and independent of the source, TAF are spindle-shaped stromal cells with negative CD34 expression. Other markers of BM-MSC such as CD105 and CD146 could be present in TAF.In previous work we found that SSC, not associated with the vasculature, sampled from early (I/II) breast cancer patients (BCP), express RANKL and RANK at significantly higher levels vs. non-neoplastic breast tissues. Also, RANK expression in these SSC had a significant association with RANKL expression in these SSC and in tumor cells of these BCP. These SSC were CD34(-) and CD105(+) like TAF and MSC.Recently work showed that RANKL is a critical molecule for BM-MSC clonogenic and differentiation potential, in particular osteogenic. Other authors found that RANKL soluble induced a migratory response in osteoblasts and osteoblast progenitors (MSC and pre-osteoblasts). The aim of this study is to explore the clinicopathological significance of RANK in these SSC, as prognostic determinants of early BCP.We conducted immunohistochemical analysis for RANK expression in these SSC of primary tumors from early BCP (invasive ductal), and analyzed their association with clinicopathological characteristics. Here, we demonstrate that the elevated level of RANK in these SSC was significantly associated with a higher risk of metastatic occurrence (0.0119). Moreover, high expression of RANK was associated with shorter disease-free survival and metastasis-free survival (p = 0.007 and 0.014). This study is the first to demonstrate that high levels of RANK expression in SSC, not associated with the vasculature, could be used to identify early BCP with poor outcomes.