Associations of B7-H3 and B7-H4 Expression in Ductal Carcinoma In Situ of the Breast With Clinicopathologic Features and T-Cell Infiltration

B7-H3 and B7-H4 play an inhibitory role in T-cell function by limiting proliferation and cytokine production. Information about B7-H3 and B7-H4 expression in ductal carcinoma in situ (DCIS) remains uncertain. The objective of this study was to evaluate the expression levels of B7-H3 and B7-H4 in DCIS and their associations with clinicopathologic features and T-cell infiltration. B7-H3 and B7-H4 mRNA and protein expression levels in 8 pairs of DCIS tissues and matched normal adjacent tissues were examined by RNAscope in situ hybridization and immunohistochemistry analysis. Immunohistochemical staining of B7-H3, B7-H4, CD3, and CD8 was performed for 79 DCIS samples using tissue microarray. RNAscope in situ hybridization and immunohistochemistry analysis revealed that expression levels of B7-H3 and B7-H4 in DCIS tissues were higher than those in corresponding normal tissues. B7-H3 and B7-H4 mRNA and protein appeared to be mainly expressed in DCIS carcinoma cells. High B7-H3 and B7-H4 expression was observed in 58 (73.4%) and 62 (78.5%) cases with DCIS, respectively. High B7-H3 expression was significantly associated with high-nuclear grade and presence of comedo-type necrosis (both P<0.05). B7-H3 expression in HR-/HER2(+) subtype was higher than that in HR+/HER2(-) subtype (P<0.05). B7-H3 and B7-H4 expression levels were negatively related to the density of CD3(+) and CD8(+) T-cell infiltrates. B7-H3 and B7-H4 may play an important role in immune surveillance mechanisms of DCIS. They might be useful targets to develop immune-based therapy to alter or prevent DCIS progression.