外阴阴道上皮肿瘤在母马中并不常见，并且仍然缺乏上皮间质转化（EMT）和肿瘤免疫微环境（TIME）的数据。这是一项研究马马乳头瘤病毒 2 型 (EcPV2) 感染状态以及母马外阴阴道肿瘤前/良性 (8/22) 或恶性 (14/22) 上皮病变的 EMT 过程和肿瘤微环境。为此，进行了组织病理学、免疫组织化学、转录组学、原位杂交和相关分析。免疫组织化学定量显示，细胞质E-cadherin和β-catenin表达以及核β-catenin表达是恶性病变的特征，而良性/癌前病变主要以膜部E-cadherin和β-catenin表达为特征。尽管如此，良性和恶性马外阴阴道病变在涉及经典和非经典wnt/β-连环蛋白途径的下游基因的表达方面没有差异。此外，恶性病变的特征是具有细胞质细胞角蛋白表达的细胞数量较少以及细胞质波形蛋白免疫标记稍高。恶性病变的TIME特征是CD204 M2极化巨噬细胞数量较多。总而言之，我们的结果支持这样的假设，即 TIME 中的一些参与者（例如 CD204 M2 极化巨噬细胞）可能有利于马外阴阴道恶性病变的 EMT 过程，为马 EcPV2 诱导的生殖器肿瘤病变领域的未来研究提供新的见解。

Vulvo-vaginal epithelial tumors are uncommon in mares, and data on the epithelial-to-mesenchymal transition (EMT) and the tumor-immune microenvironment (TIME) are still lacking. This is a study investigating the equus caballus papillomavirus type 2 (EcPV2) infection state as well as the EMT process and the tumor microenvironment in vulvo-vaginal preneoplastic/ benign (8/22) or malignant (14/22) epithelial lesions in mares. To do this, histopathological, immunohistochemical, transcriptomic, in situ hybridization, and correlation analyses were carried out. Immunohistochemistry quantification showed that cytoplasmic E-cadherin and β-catenin expression as well as nuclear β-catenin expression were features of malignant lesions, while benign/preneoplastic lesions were mainly characterized by membranous E-cadherin and β-catenin expression. Despite this, there were no differences between benign and malignant equine vulvo-vaginal lesions in the expression of downstream genes involved in the canonical and noncanonical wnt/β-catenin pathways. In addition, malignant lesions were characterized by a lower number of cells with cytoplasmic cytokeratin expression as well as a slightly higher cytoplasmic vimentin immunolabeling. The TIME of malignant lesions was characterized by more numerous CD204+ M2-polarized macrophages. Altogether, our results support the hypothesis that some actors in TIME such as CD204+ M2-polarized macrophages may favor the EMT process in equine vulvo-vaginal malignant lesions providing new insights for future investigations in the field of equine EcPV2-induced genital neoplastic lesions.