Research ArticlesAssociations of B7-H3 and B7-H4 Expression in Ductal Carcinoma In Situ of the Breast With Clinicopathologic Features and T-Cell InfiltrationKim, Nah Ihm MD, PhD*; Park, Min Ho MD, PhD†; Lee, Ji Shin MD, PhD*Author Information Departments of *Pathology †Surgery, Chonnam National University Medical School, Gwangju, South Korea Supported by a grant (HCRI 19 001-119013) from Chonnam National University Hwasun Hospital Institute for Biomedical Science. This article was presented in part at the 2018 San Antonio Breast Cancer Symposium, TX, December 4–8, 2018. The authors declare no conflict of interest. Reprints: Ji Shin Lee, MD, PhD, Department of Pathology, Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do 58128, Republic of Korea (e-mail: [email protected]). Applied Immunohistochemistry & Molecular Morphology: November/December 2020 - Volume 28 - Issue 10 - p 767-775 doi: 10.1097/PAI.0000000000000817 Buy Metrics Abstract 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. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.