Expression of Adenosine Receptors in Young Patients with Breast Cancer and its Association with High Proliferative Index

Document Type : Original Article

Authors

1 Pathology Department, Alexandria University, Alexandria, Egypt

2 Basic Medical Sciences, University of Sharjah, Sharjah, PO BOX 27272, United Arab Emirates.

Abstract

Background: Adenosine is produced in the hypoxic tumor milieu. By stimulating its receptors, it plays an important role not only in evading the body’s immune mechanisms but also in enhancing tumor vasculature and contributing to tumor aggressiveness. Aim: The present study aimed at investigating the immunohistochemical expression of Adenosine receptors (A2A) in breast cancer tissue and its association with different clinico-pathological parameters. Materials and Methods: Thirty formalin-fixed paraffin-embedded (FFPE) breast cancer specimens were immunohistochemically stained using A2AR antibodies. All clinical and pathological data were retrospectively retrieved from the patients’ records. Results: Cytoplasmic expression of A2ARs was noted not only on the tumor immune cells but also on the tumor cells themselves. They were strongly expressed on the tumor cells in 73.3% (n=22) of tumors. Expression was significantly higher in younger aged patients (< 50 years old) compared to older ones [p=0.044]. A2AR expression was also significantly higher in Luminal B and triple negative compared to Luminal A tumors [p=0.028]. The majority of A2AR expressing tumors had a mitotic index score of 2 [p=0.013] as well as a significantly higher proliferative index (ki-67 >20%) [p=0.018]. No association was observed between A2AR expression and tumor size, type, grade, Lymph node status, percentage of TILs or patient survival after 2 years of follow-up. Conclusion: These findings suggest a possible role for Adenosine in imparting a more aggressive phenotype in breast cancer and that targeting these receptors using Adenosine receptor antagonists could have a potential role in improving the outcome of these patients.

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