Abstract P4-06-25: B7-H3 and B7-H4 expression in ductal carcinoma in situ of the breast: Associations with clinicopathologic features and T-cell infiltration

Abstract

Abstract Background: With the clinical success of immune check point blockades in treating malignant tumors, there are intense investigations in identifying new pathways to activate immune system by targeting immunoregulatory molecules. B7-H3 and B7-H4 play an inhibitory role in T cell function by limiting proliferation and cytokine production. Although several studies have investigated the expression of B7-H3 and B7-H4 in invasive breast cancers, the information of the B7-H3 and B7-H4 molecules in ductal carcinoma in situ (DCIS) remains uncertain. The present work was undertaken to evaluate the expression of B7-H3 and B7-H4 in DCIS and its association with clinicopathological features in patients with DCIS. In addition, the association of B7-H3 and B7-H4 expression with the T-cell infiltration was also assessed to investigate its roles in the regulation of tumor immune surveillance. Materials and methods: B7-H3 and B7-H4 expression was examined in 8 pairs of DCIS tissues and matched normal adjacent tissues at mRNA and protein levels by RNAscope in situ hybridization (ISH) and immunohistochemistry. Immunohistochemical staining of B7-H3 and B7-H4 was done in 79 DCIS samples with known hormone receptor (HR) and human epidermal growth factor 2 (HER2) expression using tissue microarray. In addition, immunohistochemical staining was also performed for the T cell lineage markers CD3 and CD8 in DCIS. Results: RNAscope ISH and immunohistochemistry of B7-H3 and B7-H4 confirmed their increases in DCIS tissues compared with their corresponding normal tissues. B7-H3 and B7-H4 mRNA and protein expression appeared to be concentrated mainly in the 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 (P < 0.05 and P < 0.05, respectively). B7-H3 expression was higher in the HR–/HER2+ subtypes than in the HR+/HER2– subtype (P < 0.05). B7-H3 and B7-H4 expression tended to be associated with low stromal tumor infiltrating lymphocytes density and was negatively related to the CD3+ and CD8+ T cell infiltrates density. Conclusions: These results suggest that B7-H3 and B7-H4 may play an important role in immune surveillance mechanisms of DCIS and may be useful targets for immune-based therapy to alter or prevent DCIS progression. Citation Format: Lee JS, Kim G-E, Park MH, Yoon JH. B7-H3 and B7-H4 expression in ductal carcinoma in situ of the breast: Associations with clinicopathologic features and T-cell infiltration [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-25.