Department of Diagnostic Pathology, Faculty of Medicine, Oita University, Oita, Japan.
Department of Diagnostic Pathology, Faculty of Medicine, Oita University, Oita, Japan.
Exp Mol Pathol. 2024 Oct;139:104917. doi: 10.1016/j.yexmp.2024.104917. Epub 2024 Jul 24.
Breast cancer (BC) is classified into four major histological subtypes, namely luminal A, luminal B, HER2, and basal-like, and its treatment is based on these subtypes. The use of immune checkpoint inhibitors against BC depends on the expression of PD-1/PD-L1. Another tumor immune system-the cGAS-STING pathway-is a potential target for cancer immunotherapy. However, the status of the cGAS-STING pathway in BC has not been fully established. Therefore, we investigated the expression status of the cGAS-STING pathway and immune-related proteins in BC. We classified 111 BCs into six groups-29 hormone receptor-positive carcinomas, 12 HER2+ carcinomas (HER2), 8 luminal-HER2 carcinomas, 26 triple-negative breast carcinomas (TNBCs), 21 lobular carcinomas (LC), and 15 carcinomas with apocrine differentiation (CAD)-and investigated the relationship between BC and tumor immunity via the cGAS-STING pathway using histopathological and immunohistochemical methods. Expression of cGAS was high in CADs (100%) and low in TNBCs (35%); STING-positive lymphocytes were high in TNBC (85%, P = 0.0054). Expression of pSTAT3 was significantly high in patients with TNBC (≥10%, 88%). The proportion of PD-L1-positive tumor cells was higher in TNBCs (54%) than in other BCs (30%). SRGN expression was significantly higher in the TNBC group than in the other BC groups (58%). Tumor immune responses may differ among tumor subtypes. The cGAS-STING pathway may be functional in TNBC and CAD but not in LC. Therefore, targeting the cGAS-STING pathway might be useful in BC, particularly TNBC and CAD.
乳腺癌（BC）分为四大组织学亚型，即 luminal A、luminal B、HER2 和基底样型，其治疗基于这些亚型。免疫检查点抑制剂在 BC 中的应用取决于 PD-1/PD-L1 的表达。另一个肿瘤免疫系统——cGAS-STING 通路——是癌症免疫治疗的潜在靶点。然而，BC 中 cGAS-STING 通路的状态尚未完全确定。因此，我们研究了 cGAS-STING 通路和免疫相关蛋白在 BC 中的表达情况。我们将 111 例 BC 分为六组——29 例激素受体阳性癌、12 例 HER2+癌（HER2）、8 例 luminal-HER2 癌、26 例三阴性乳腺癌（TNBC）、21 例小叶癌（LC）和 15 例具有大汗腺癌分化的癌（CAD），并通过组织病理学和免疫组织化学方法研究了 cGAS-STING 通路在 BC 与肿瘤免疫之间的关系。CAD 中 cGAS 的表达较高（100%），而 TNBC 中表达较低（35%）；STING 阳性淋巴细胞在 TNBC 中较高（85%，P=0.0054）。pSTAT3 的表达在 TNBC 患者中显著升高（≥10%，88%）。PD-L1 阳性肿瘤细胞的比例在 TNBC 中（54%）高于其他 BC （30%）。SRGN 表达在 TNBC 组明显高于其他 BC 组（58%）。肿瘤免疫反应在不同的肿瘤亚型之间可能存在差异。cGAS-STING 通路在 TNBC 和 CAD 中可能有功能，但在 LC 中可能没有功能。因此，针对 cGAS-STING 通路可能对 BC 特别是 TNBC 和 CAD 有用。
