Increased ager expression in inflammatory breast cancer: a comparative study with non-ibc patients

Introduction: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer characterized by erythema, edema, and skin changes such as nipple inversion and peau d’orange. These symptoms are primarily due to the presence of numerous dermal tumor emboli that obstruct lymphatic drainage. Despite the distinct symptomatology between IBC and non-IBC, the molecular differences between these two forms of breast cancer remain largely unexplored. The Advanced Glycation End Product Receptor (AGER/RAGE) is a transmembrane receptor overexpressed in various cancers, is associated with epithelial-to-mesenchymal transition, and has been implicated in breast cancer pathogenesis. The overexpression of AGER is linked to rapid tumor progression and metastasis.

Objective: To measure and compare the levels of AGER expression in patients with IBC and non-IBC.

Method: Indirect immunofluorescence was analyzed in 35 samples (19 IBC and 16 non-IBC). Both sample types were stained with DAPI, which binds to the nuclear area, and an anti-AGER monoclonal antibody, which binds to the receptor. Four fields were selected for each sample, and AGER expression was quantified as a percentage of the immunofluorescence intensity area. The expression data and clinicopathological parameters were compared, including the prognostic values of these biomarkers. The transcriptomic data of IBC and non-IBC microarray data from the Gene Expression Omnibus repository (GEO) were used to investigate the expression of AGER genes.

Results: Tumor samples from IBC patients showed higher AGER immunoexpressions than the non-IBC group and were associated with obesity and Ki-67 expression (p <0.05). AGER expression in IBC versus non-IBC was also statistically associated with triple-negative molecular subtypes. External validation by analyzing three external GEO datasets confirmed the higher expression of AGER in IBC than in non-IBC samples.

Conclusion: Overall, tumor samples from IBC patients showed higher AGER expressions than other breast cancer types.

Corresponding author: Pedro Ruan Amorim de Oliveira Costa (e-mail: pedroruan@alu.ufc.br).