Vulvo-vaginal epithelial tumors in mares: A preliminary investigation on epithelial-mesenchymal transition and tumor-immune microenvironment.
Authors: Armando Federico, Porcellato Ilaria, de Paolis Livia, Mecocci Samanta, Passeri Benedetta, Ciurkiewicz Małgorzata, Mechelli Luca, Grazia De Ciucis Chiara, Pezzolato Marzia, Fruscione Floriana, Brachelente Chiara, Montemurro Vittoria, Cappelli Katia, Puff Christina, Baumgärtner Wolfgang, Ghelardi Alessandro, Razzuoli Elisabetta
Journal: Veterinary pathology
Summary
Vulvo-vaginal epithelial tumours remain poorly characterised in mares, particularly regarding the cellular and immunological mechanisms that drive malignant transformation from benign or preneoplastic lesions. Researchers examined 22 equine genital tissue samples (8 benign/preneoplastic, 14 malignant) using histopathology, immunohistochemistry, transcriptomic analysis, and in situ hybridisation to investigate epithelial-mesenchymal transition (EMT) markers, equine papillomavirus type 2 (EcPV2) infection status, and the tumour-immune microenvironment. Malignant lesions displayed abnormal subcellular localisation of adhesion molecules—specifically cytoplasmic and nuclear β-catenin and E-cadherin shifts from their normal membranous distribution—suggesting EMT activation, though downstream wnt/β-catenin pathway genes showed no differential expression between benign and malignant cases. The key immunological finding was a significantly higher infiltration of CD204+ M2-polarised macrophages in malignant lesions, along with reduced cytokeratin and slightly elevated vimentin expression. For practitioners managing mares with genital neoplasia, these findings suggest that tumour-associated macrophage populations may represent both a biomarker for malignancy and a potential therapeutic target, whilst the presence of EcPV2 warrants further investigation as a contributing factor in genital tumour development.
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Practical Takeaways
- •CD204+ M2 macrophage infiltration may serve as a prognostic marker to distinguish malignant from benign vulvo-vaginal lesions in mares
- •Immunohistochemical patterns of E-cadherin and β-catenin localization (membranous vs. cytoplasmic/nuclear) can help differentiate tumor grade in routine diagnostic work
- •Future treatment strategies targeting tumor-immune microenvironment modulation may offer therapeutic potential for EcPV2-induced genital neoplasias in mares
Key Findings
- •Malignant vulvo-vaginal lesions showed cytoplasmic and nuclear β-catenin expression, while benign/preneoplastic lesions had membranous expression patterns
- •CD204+ M2-polarized macrophages were significantly more numerous in malignant lesions compared to benign lesions
- •Malignant lesions exhibited lower cytoplasmic cytokeratin expression and slightly higher vimentin immunolabeling, suggesting epithelial-mesenchymal transition features
- •No differences in downstream Wnt/β-catenin pathway gene expression between benign and malignant lesions despite morphological differences