Department of General Pathology, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Belo Horizonte, Minas Gerais, CEP: 31270-901, Brazil.
Department of Morphology, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Belo Horizonte, Minas Gerais, CEP: 31270-901, Brazil.
BMC Vet Res. 2021 Mar 24;17(1):130. doi: 10.1186/s12917-021-02807-y.
Invasive micropapillary carcinoma (IMPC) is a rare malignant breast tumor and a variant form of invasive ductal carcinoma that is an aggressive neoplasm of the human breast and canine mammary gland. The importance of the tumor microenvironment in cancer development has gradually been recognized, but little is known about the cell types outlining the cystic space of canine IMPC. This study aimed to characterize the neoplastic cells outlining the cystic space of IMPC.
Immunohistochemistry (IHC), immunofluorescence (IF), superresolution and transmission electron microscopy (TEM) were used to assess the cell types in the cystic areas of IMPCs. Cells expressing the mesenchymal markers alpha-smooth muscle actin (αSMA), Vimentin, and S100A4 outlined the cystic space of IMPC. Furthermore, loss of epithelial cell polarity in IMPC was shown by the localization of MUC1 at the stroma-facing surface. This protein modulates lumen formation and inhibits the cell-stroma interaction. Immunohistochemical and IF staining for the myoepithelial cell marker p63 were negative in IMPC samples. Furthermore, associated with peculiar morphology, such as thin cytoplasmic extensions outlining cystic spaces, was observed under TEM. These observations suggested cells with characteristics of myoepithelial-like cells.
The cells outlining the cystic space of IMPC in the canine mammary gland were characterized using IHC, IF and TEM. The presence of cells expressing αSMA, Vimentin, and S100A4 in the IMPC stroma suggested a role for tumor-associated fibroblasts in the IMPC microenvironment. The reversal of cell polarity revealed by the limited basal localization of MUC1 may be an important factor contributing to the invasiveness of IMPC. For the first time, the cystic space of canine mammary gland IMPC was shown to be delimited by myoepithelial-like cells that had lost p63 expression. These findings may enhance our understanding of the cellular microenvironment of invasive tumors to improve cancer diagnosis and treatment.
浸润性微乳头状癌（IMPC）是一种罕见的恶性乳腺肿瘤，也是一种侵袭性的人类乳腺和犬乳腺导管癌的变体。肿瘤微环境在癌症发展中的重要性逐渐得到认可，但对犬 IMPC 囊腔周围的细胞类型知之甚少。本研究旨在描述 IMPC 囊腔周围的肿瘤细胞。
免疫组织化学（IHC）、免疫荧光（IF）、超分辨率和透射电子显微镜（TEM）用于评估 IMPC 囊腔中的细胞类型。表达间充质标志物α-平滑肌肌动蛋白（αSMA）、波形蛋白和 S100A4 的细胞勾勒出 IMPC 的囊腔。此外，在 IMPC 中上皮细胞极性的丧失表现为 MUC1 位于基质面向的表面。这种蛋白调节管腔形成并抑制细胞-基质相互作用。在 IMPC 样本中，免疫组织化学和 IF 染色对肌上皮细胞标志物 p63 为阴性。此外，与 TEM 下观察到的特有的形态相关，如薄的细胞质延伸勾勒出囊腔。这些观察结果表明存在具有肌上皮样细胞特征的细胞。
使用 IHC、IF 和 TEM 对犬乳腺 IMPC 囊腔周围的细胞进行了特征描述。在 IMPC 基质中表达αSMA、波形蛋白和 S100A4 的细胞的存在表明肿瘤相关成纤维细胞在 IMPC 微环境中的作用。MUC1 有限的基底定位所揭示的细胞极性逆转可能是促进 IMPC 侵袭性的重要因素。首次显示犬乳腺 IMPC 的囊腔由丧失 p63 表达的肌上皮样细胞限定。这些发现可能有助于我们了解侵袭性肿瘤的细胞微环境，以改善癌症诊断和治疗。
