CONICET | Buscador de Institutos y Recursos Humanos

Once breast cancer metastasizes to bone, mortality increases. Thus, there is an urgent need to identify patients with high risk to develop bone metastases at earlier-stage of disease. Several studies in breast cancer have confirmed that tumour-extracellular matrix and non-carcinoma cells, mainly cancer-associated fibroblasts, mesenchymal stem cells and inflammatory cells drive cancer progression and bone metastasis development. The aim of our research was to investigate their prognostic significance in untreated early-breast cancer patients. Therefore, we analyzed immunohistochemical expression of α-SMA and FSP (cancer-associated fibroblast-markers) and CD105 and CD146 (mesenchymal stem cell-markers) in stromal cells of 41 primary tumours of untreated-breast cancer patients with infiltrative ductal carcinoma (I/II stage) and 10 non-malignant breast tissues and investigated whether their expression and stromal features are associated with classical-prognostic markers, bone metastasis occurrence and skeletal disease-free survival of these patients. In this study, we demonstrated that high CD105 expression associates with bone metastases occurrence (p=0.0242) and shorter skeletal disease-free survival (p=0.0180). Moreover, we postulated it as an independent marker for early bone breast cancer-development (p=0.0440). Finally, we found statistically significant association of high values of lymphocytic infiltrate with positive-HER2/neu (p=0.0138) and myxoid changes with high tumour size, poor differentiated tumours and positive-HER2/neu (p=0.0373, 0.0004 and 0.0310; respectively). In conclusion, this is the first demonstration of stromal-CD105 expression in primary tumours as an early marker of bone metastasis recurrence and shorter skeletal disease-free survival in breast cancer patients. This work also support an unfavourable prognostic significance of lymphocytic infiltration and myxoid changes in their tumours. PREMIADO