Evaluation of receptor for advanced glycation end product /high-mobility group box 1 (RAGE/HMGB1) expression status and its prognostic value in breast cancer

Sucess in breast cancer treatment is not built only on diversity but on clinical relevance to tumor pathogenesis. So, gathering of many prognositic biomarkers involved in cancer progression could yield new treatment modalities in order to maitain good quality of life for patients .The receptor for advanced glycation end product (RAGE) and its ligand the high-mobility group box 1 (HMGB1) protein seem to play a role in many cancers , their cross-talk affects breast cancer behaviour. The aim of this study was to investigate the tissue RAGE and HMGB1 expression levels and their association with clinico-pathological features and overall survival in breast cancer patients.Tissue RAGE and HMGB1 mRNA levels were measured by real time-polymerase chain reaction (RT-PCR). Results showed tissue RAGE and HMGB1 displayed significant higher expression levels compared to benign group. RAGE and HMGB1 expression levels in breast cancer tissues were significantly associated with high tumour grade , lymph node metastasis ,stage III wih no significant relation to the molecular type of tumor nor overall survival. RAGE-HMGB1 system seems to be linked to breast cancer which may represent a prognostic biomarker of clinical and theraputic significance.Keywords: Breast cancer, RAGE, HMGB1, RT-PC

Characterization of the Immune Microenvironment in Inflammatory Breast Cancer Using Multiplex Immunofluorescence

Introduction: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with a poorly characterized immune microenvironment. Methods: We used a five-colour multiplex immunofluorescence panel, including CD68, CD4, CD8, CD20, and FOXP3 for immune microenvironment profiling in 93 treatment-naïve IBC samples. Results: Lower grade tumours were characterized by decreased CD4+ cells but increased accumulation of FOXP3+ cells. Increased CD20+ cells correlated with better response to neoadjuvant chemotherapy and increased CD4+ cells infiltration correlated with better overall survival. Pairwise analysis revealed that both ER+ and triple-negative breast cancer were characterized by co-infiltration of CD20 + cells with CD68+ and CD4+ cells, whereas co-infiltration of CD8+ and CD68+ cells was only observed in HER2+ IBC. Co-infiltration of CD20+, CD8+, CD4+, and FOXP3+ cells, and co-existence of CD68+ with FOXP3+ cells correlated with better therapeutic responses, while resistant tumours were characterized by co-accumulation of CD4+, CD8+, FOXP3+, and CD68+ cells and co-expression of CD68+ and CD20+ cells. In a Cox regression model, response to therapy was the most significant factor associated with improved patient survival. Conclusion: Those results reveal a complex unique pattern of distribution of immune cell subtypes in IBC and provide an important basis for detailed characterization of molecular pathways that govern the formation of IBC immune landscape and potential for immunotherapy