Descriptive study of stromal expression of CD73 in ductal carcinoma in situ of the breast

Cancer-associated fibroblasts (CAFs) could act as a source of resistance to anti-tumor immune response. CD73 is an ectoenzyme that promotes tumour immune escape by producing immunosuppressive extracellular adenosine in the tumour microenvironment. In addition, CD73 is an adhesion molecule binding to other cells and extracellular matrix and facilitates cell motility. Nevertheless, CD73 functions in CAFs remain poorly investigated. Furthermore, it has never been studied in the stroma around lesions of ductal carcinoma in situ (DCIS). We performed this study to determine the expression of CD73 in the stroma of DCIS.

The present retrospective study included 28 cases of pure DCIS (not associated with an invasive component). For each case of DCIS, all the foci were graded and analysed separately, representing a total of 450 foci of DCIS. The immunoreactivity of CD73 was assessed semi-quantitatively. The percentage of stromal cells expressing each antigen was graded as score 0, score 1, score 2, and score 3 when up to 5%, more than 5%, and up to 25%, more than 25%, and up to 50% or more than 50% of stromal cells, disclosed immunoreactivity, respectively.

An association was observed between DCIS grade and stromal CD73 expression; however, given the clustered nature of the data, these findings should be interpreted as exploratory. CD73 expression was more frequent in intermediate and high-grade lesions than in low-grade lesions (p < 0.001). When necrosis was present, CD73 expression was higher than in lesions without necrosis in the case of intermediate grade (p < 0.01) but not in the case of high grade.

This study, to our knowledge, is the first to demonstrate CD73 expression around ductal carcinoma in situ (DCIS). We found a statistically significant difference in the stromal expression of CD73 based on the grade of DCIS. Additionally, there is a link between necrosis and intermediate-grade lesions, but not with high-grade lesions. These findings need further confirmation, as our analysis was limited to only 28 cases. Future research could explore the role of chemoprevention using anti-CD73 agents to potentially prevent the progression of DCIS to invasive breast cancer, which may be beneficial for patients who are unable or unwilling to undergo surgery.