Abstract
PURPOSE: CD39 (ENTPD1, ectonucleoside triphosphate diphosphohydrolase-1) and CD73 (NT5E, 5'-nucleotidase) are mediators of adenosine release in the tumor microenvironment (TME), and adenosine has the effect of overcoming anti-tumor immunity. This CD39-CD73-adenosine pathway is thought that play a role in immune suppression and promotion of tumor growth and infiltration. This study investigated the clinical and prognostic significance of CD39 and CD73 in breast cancer. METHODS: This study included 472 patients with primary invasive breast cancer who received surgical treatment at the Breast Cancer Clinic at Chung-Ang University Hospital from June 2010 to May 2017. Using a tissue microarray, biomarker immunostaining was performed for CD39 and CD73. We assessed the expression ratio of CD39 and CD73 in breast cancer subgroups, and investigated the association between disease-free survival (DFS) and the expression of CD39 and CD73. RESULTS: The expression ratio of CD39 and CD73 in breast cancer subgroups differed according to hormone receptor status and human epidermal growth factor receptor 2 (HER2) status. In the case of CD39, the high-level rate was increased in estrogen receptor (ER)/progesterone receptor (PR) positive (p = 0.001, p = 0.009), and HER2 negative (p < 0.001) breast cancer. In contrast, in the case of CD73 expressed in tumor-infiltrating lymphocyte (TIL), the expression rate was increased in ER/PR negative (p < 0.001), and HER2 positive (p < 0.001), breast cancer. High CD39 expression was significantly associated with lower stage (p < 0.001), but there was no relationship CD39 expression and survival. In patients with HER2-positive breast cancer, CD73 expression in TIL was associated with lower stage (p = 0.024), and better survival in DFS analysis (p = 0.015). CONCLUSION: In conclusion, the expression ratio of CD39 and CD73 in breast cancer subgroups differed according to hormone receptor status and HER2 status, and CD73 expression in TILs associated with a trend toward favorable prognosis in HER2 positive breast cancer.