Adenosine A2A Receptor Expression in Tumor Cells and Stromal Tumor-Infiltrating Lymphocytes in Invasive Breast Carcinoma of No Special Type (NST)

Background: Breast cancer (BC) is a very critical health concern, as it is the leading cause of global cancer incidence and female cancer-related deaths worldwide. Despite the clinically successful outcome of immunotherapy, there are always considerable concerns about the initial or eventual failure to control the disease. Adenosine 2A receptors (A2AR) play an essential role in protecting tissues against excessively indulgent immune reactions. The scope of this study is to evaluate the immunohistochemical expression of adenosine receptor A2A in invasive breast carcinoma and its association with clinicopathological parameters. Materials and Methods: A retrospective cross-sectional tissue-biomarker study of 50 cases of invasive breast carcinoma of no special type (NST), archived as formalin-fixed paraffin-embedded blocks stained immunohistochemically for A2AR. Of the 50 cases, 26 were obtained following neoadjuvant chemotherapy. Cases were divided according to A2AR expression using a cutoff of 100 to low (<100) and high (≥100) A2AR expression. Results: High A2AR was detected in 30% of tumor cells (TCs) in the studied cases. High A2AR expression in TCs was significantly associated with high A2AR expression in tumor-infiltrating lymphocytes (TILs) and with a high Ki-67 proliferation index. Conclusions: In conclusion, this exploratory study showed that A2AR is expressed in both TCs and TILs, with a positive association between A2AR expression in TCs and in TILs. High A2AR expression in TCs was also associated with high Ki-67 proliferative activity. These associations persisted after adjustment for neoadjuvant chemotherapy, but they do not establish causality. They support further investigation of A2AR as a potential immunotherapeutic target in larger, independent studies.