Open AccessComparison of the Clinicopathologic Features and T-Cell Infiltration of B7-H3 and B7-H4 Expression in Triple-negative Breast Cancer Subtypes
Author(s) -
Nah Ihm Kim,
Min Ho Park,
Namki Cho,
Ji Shin Lee
Publication year - 2021
Publication title -
applied immunohistochemistry and molecular morphology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.868
H-Index - 60
eISSN - 1541-2016
pISSN - 1533-4058
DOI - 10.1097/pai.0000000000001001
Subject(s) - stromal cell , immunohistochemistry , tissue microarray , breast cancer , triple negative breast cancer , cancer research , cd8 , in situ hybridization , biology , pathology , tumor infiltrating lymphocytes , cd3 , messenger rna , cancer , medicine , antigen , immunology , gene , biochemistry
Previously we revealed an upregulated expression of B7-H3 and B7-H4 mRNA and protein in breast cancer, including triple-negative breast cancer (TNBC). However, little is known regarding the clinical impact and value of B7-H3 and B7-H4 in TNBC subtypes. Thus, this study evaluated the clinicopathologic effects of B7-H3 and B7-H4 mRNA and protein expression according to the TNBC subtypes. RNAscope in situ hybridization and immunohistochemistry of B7-H3 and B7-H4 was done for 186 TNBC samples using tissue microarray. Immunohistochemistry was also performed for TNBC molecular subtype-surrogate markers, CD3, and CD8. TNBCs were classified into basal-like (BL) (64.5%), luminal androgen receptor (10.8%), and unclassifiable (24.7%) subtypes. Tumor B7-H4 mRNA expression was associated with younger age at the initial diagnosis and with molecular TNBC subtypes. Expression of B7-H3 mRNA and protein in the tumor cells was negatively correlated with CD3+ and CD8+ T-cell infiltration density in the tumor and/or stromal region of TNBCs and their subtypes. High stromal B7-H3 mRNA expression was associated with poor disease-free and overall survival in the TNBCs and with overall survival in the unclassifiable subtype. Stromal B7-H3 mRNA expression was independently associated with overall survival and disease-free survival in the TNBCs and BL subtype, respectively. Our results indicate the importance of the stromal expression of B7-H3 mRNA as a prognostic factor in the TNBCs and BL subtype. The inverse relationship between B7-H3 expression and CD3+ and CD8+ T-lymphocyte infiltration represents a promising target for immunotherapy for the TNBCs, especially the BL subtype.