Abstract PS17-35: B7-H3 and B7-H4 expression in triple-negative breast cancer subtypes detected by RNA in situ hybridization and immunohistochemistry: Association with clinicopathological features and T-cell infiltration
Authors: Lee Ji Shin , Kim Nah Ihm , Park Min Ho 
Published: February 2021

Abstract
Background: Triple-negative breast cancer (TNBC) is a heterogeneous group of cancer with dismal prognosis. B7 families can be promising targets for cancer immunotherapy in TNBC. Previously we have found increased expression of B7-H3 and B7-H4 mRNA and protein in breast cancer including TNBC. In an effort to discover therapeutic targets, TNBC has been further stratified into molecular subtypes. However, little is known about the clinical impact and value of B7-H3 and B7-H4 in TNBC subtypes. The purpose of this study was to evaluate the clinicopathologic characteristics of the B7-H3 and B7-H4 mRNA and protein expression according to the TNBC subset. Materials and methods: A tissue microarray was constructed from 186 patients with TNBC. B7-H3 and B7-H4 mRNA and protein expression were assessed by the RNAscope in situ hybridization (ISH) and immunohistochemistry. Immunohistochemistry for the TNBC molecular subtype-surrogate markers [cytokeratin 5/6 (CK5/6), CK14, epidermal growth factor receptor (EGFR), and androgen receptor (AR)], CD3, and CD8 was also performed. TNBC subtypes were classified into three subtypes: basal-like (BL), luminal AR (LAR), and unclassifiable type (UN). Results: Based on the immunohistochemical results, 186 TNBCs were classified into BL (n=120, 64.5%), LAR (n=10, 10.8%), and UN (n=46, 24.7%) subtypes. BL and UN subtypes were associated with younger age than the LAR subtype. B7-H3 mRNA and protein expressions were expressed in the tumor and stromal cells of the TNBCs. On the contrary, B7-H4 mRNA and protein expressions were only observed in the tumor cells. High tumor mRNA and protein expression of B7-H3 and B7-H4 were found in 49 of 175 (28.0%) and 121 of 176 (68.8) cases, and 92 of 174 (52.9%) and 66 of 176 (37.5%) cases, respectively. High stromal B7-H3 mRNA and protein expression were observed in 22 of 175 (12.6%) and 43 of 176 (24.4%) cases. High stromal B7-H4 mRNA and protein expression were not observed. B7-H3 and B7-H4 protein expression were closely correlated with their mRNA expression according to the tumor compartment. Tumor B7-H4 mRNA expression was associated with younger age at the initial diagnosis and molecular TNBC subtypes. Expression of B7-H3 mRNA and protein in the tumor cells negatively correlated with CD3+ and CD8+ T cell infiltration density in the tumor and/or stromal compartment of the TNBCs and its subtypes. High stromal B7-H3 mRNA expression was associated with poor disease-free and overall survival in the TNBCs and overall survival in the UN subtype. Stromal B7-H3 mRNA expression was independently associated with overall survival in the TNBCs and disease-free survival in the BL subtype. Conclusions: As prognostic factors, our results point to the importance of the expression of B7-H3 mRNA by the stromal cells in the TNBCs and the BL subtype. The inverse relationship between B7-H3 expression and CD3+ and CD8+ T lymphocyte infiltration may represent a promising target in the immunotherapy of the TNBCs, irrespective of its molecular subtypes.
Citation Format: Ji Shin Lee, Nah Ihm Kim, Min Ho Park. B7-H3 and B7-H4 expression in triple-negative breast cancer subtypes detected by RNA in situ hybridization and immunohistochemistry: Association with clinicopathological features and T-cell infiltration [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-35.