CD39 and CD73 Expression in Breast Cancer: CD73 as a Favorable Prognostic Factor in HER2-Positive Tumors

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. 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. 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). 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.