Departments of Pathology.
Surgery, Chonnam National University Medical School.
Appl Immunohistochem Mol Morphol. 2022 Apr 1;30(4):246-256. doi: 10.1097/PAI.0000000000001001.
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.
先前，我们发现 B7-H3 和 B7-H4mRNA 和蛋白在乳腺癌中表达上调，包括三阴性乳腺癌（TNBC）。然而，关于 B7-H3 和 B7-H4 在 TNBC 亚型中的临床意义和价值知之甚少。因此，本研究根据 TNBC 亚型评估了 B7-H3 和 B7-H4mRNA 和蛋白表达的临床病理影响。使用组织微阵列对 186 例 TNBC 样本进行了 B7-H3 和 B7-H4 的 RNAscope 原位杂交和免疫组织化学检测。还对 TNBC 分子亚型替代标志物 CD3 和 CD8 进行了免疫组织化学检测。将 TNBC 分为基底样（BL）（64.5%）、腔雄激素受体（10.8%）和无法分类（24.7%）亚型。肿瘤 B7-H4mRNA 表达与初始诊断时的年龄较小以及分子 TNBC 亚型相关。肿瘤细胞中 B7-H3mRNA 和蛋白的表达与 TNBC 及其亚型肿瘤和/或基质区域中 CD3+和 CD8+T 细胞浸润密度呈负相关。高基质 B7-H3mRNA 表达与 TNBC 及无法分类亚型的无病生存和总生存不良相关，与无法分类亚型的总生存相关。基质 B7-H3mRNA 表达与 TNBC 和 BL 亚型的总生存和无病生存分别独立相关。我们的研究结果表明，B7-H3mRNA 基质表达作为 TNBC 和 BL 亚型的预后因素具有重要意义。B7-H3 表达与 CD3+和 CD8+T 淋巴细胞浸润呈负相关，这代表了 TNBC，尤其是 BL 亚型免疫治疗的一个有前途的靶点。
