A hallmark of ductal carcinoma in situ (DCIS) progression is a loss of the surrounding ductal myoepithelium. However, whether compromise in myoepithelial differentiation, rather than overt cellular loss, can be used to predict the risk of DCIS progression is unknown. Here we address this question utilizing pure and mixed DCIS cases (N = 30) as surrogates for DCIS at low and high risk for progression, respectively. We used multiplex immunohistochemical staining to evaluate the relationship between myoepithelial cell differentiation and lymphoid immune cell types associated with poor prognostic DCIS. Our results show that myoepithelial calponin‐1 discriminates between pure and mixed DCIS lesions better than histological subtype, presence of necrosis, or nuclear grade. Additionally, focal loss of myoepithelial cells associated with increased PD‐1+CD8+ T cells, which suggests a link between the myoepithelium and immune surveillance. To identify associations between calponin‐1 expression and immune response, we performed unsupervised hierarchical clustering of myoepithelial and immune cell biomarkers on 219 DCIS lesions from 30 cases. Notably, the majority of pure (low‐risk) DCIS lesions clustered in a high calponin‐1, T cell low group, whereas the majority of mixed (high‐risk) DCIS lesions clustered in a low calponin‐1, T cell high group, specifically with CD8+ and PD‐1+CD8+ T cells. However, a subset of pure DCIS lesions had a similar calponin‐1 and immune signature as the majority of mixed DCIS lesions, which have low calponin‐1 and T cell enrichment—raising the possibility that these pure DCIS lesions might be at a high risk for progression.

中文翻译：

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肌上皮 calponin-1 的缺失是高危导管原位癌的特征，可根据 T 细胞组成进一步分层。


导管原位癌 (DCIS) 进展的一个标志是周围导管肌上皮的丧失。然而，肌上皮分化的损害（而不是明显的细胞损失）是否可以用来预测 DCIS 进展的风险尚不清楚。在这里，我们利用纯 DCIS 病例 (N = 30) 分别作为进展风险低和高风险的 DCIS 的替代物来解决这个问题。我们使用多重免疫组织化学染色来评估肌上皮细胞分化和与不良预后 DCIS 相关的淋巴免疫细胞类型之间的关系。我们的结果表明，肌上皮钙调蛋白-1 比组织学亚型、是否存在坏死或核分级更好地区分单纯性 DCIS 病变和混合性 DCIS 病变。此外，肌上皮细胞的局灶性丢失与 PD-1+CD8+ T 细胞增加相关，这表明肌上皮和免疫监视之间存在联系。为了确定 calponin-1 表达与免疫反应之间的关联，我们对 30 例病例中的 219 个 DCIS 病变进行了肌上皮和免疫细胞生物标志物的无监督分层聚类。值得注意的是，大多数纯（低风险）DCIS 病变聚集在高 calponin-1、T 细胞低组中，而大多数混合（高风险）DCIS 病变聚集在低 calponin-1、T 细胞高组中，特别是 CD8+ 和 PD-1+CD8+ T 细胞。然而，纯 DCIS 病变的一个子集与大多数混合性 DCIS 病变具有相似的 calponin-1 和免疫特征，而混合性 DCIS 病变的 calponin-1 和 T 细胞富集度较低，这增加了这些纯 DCIS 病变可能处于高风险的可能性为了进步。