Epithelial-mesenchymal transition in an EcPV2-positive vulvar squamous cell carcinoma of a mare.
Authors: De Paolis Livia, Armando Federico, Montemurro Vittoria, Petrizzi Lucio, Straticò Paola, Mecocci Samanta, Guarnieri Chiara, Pezzolato Marzia, Fruscione Floriana, Passeri Benedetta, Marruchella Giuseppe, Razzuoli Elisabetta
Journal: Equine veterinary journal
Summary
# Editorial Summary: EcPV2-Associated Vulvar Squamous Cell Carcinoma and Epithelial-Mesenchymal Transition in Equines Vulvar squamous cell carcinoma (VSCC) represents an emerging disease in mares, recently linked to Equus caballus papillomavirus type 2 (EcPV2) infection, yet clinical and pathological understanding remains limited. De Paolis and colleagues examined tumour tissue from a 13-year-old Haflinger presenting with rapidly progressive vulvar pathology, applying comprehensive molecular and immunohistochemical analysis to characterise not only viral involvement but also the tumour's capacity to undergo epithelial-mesenchymal transition (EMT)—a critical mechanism enabling malignant progression and metastatic potential. The researchers confirmed active EcPV2 infection with expressed oncoproteins (E6 and E7), whilst immunohistochemistry revealed hallmark EMT features including a cadherin switch and activation of the hypoxia-inducible transcription factor HIF1α; gene expression profiling demonstrated marked upregulation of N-cadherin (CDH2; 2445-fold increase) and pro-inflammatory CXCL8 (289-fold increase), alongside significant downregulation of epithelial markers (E-cadherin/CDH1; 70% reduction) and protective immunity genes (IL12A and IL17). For equine practitioners, this case establishes that EcPV2-driven VSCC exhibits aggressive biological behaviour consistent with EMT activation, suggesting that affected mares warrant early intervention and potentially more guarded prognoses than previously anticipated, whilst highlighting the need for prospective surveillance and further research into viral epidemiology, screening protocols, and whether immuno
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Practical Takeaways
- •Clinicians should consider EcPV2 infection as a causative agent in rapidly growing vulvar masses in mares, particularly when surgical excision is planned
- •The documented EMT activity in this case suggests EcPV2-positive VSCC may be more aggressive than previously understood, warranting careful post-surgical monitoring for recurrence
- •Molecular testing for EcPV2 and EMT markers could potentially help stratify risk and guide treatment decisions in future cases, though current evidence is limited to this single case
Key Findings
- •EcPV2 DNA and oncoproteins (E6/E7) were confirmed in the neoplastic vulvar lesion using real-time qPCR, RT-qPCR, and RNAscope
- •Cadherin switch and HIF1α expression indicated active epithelial-mesenchymal transition within the tumor
- •Significantly upregulated genes included EBI3 (45.0±1.62), CDH2 (2445.3±0.39), and CXCL8 (288.7±0.40), while CDH1, IL12A, and IL17 were downregulated
- •Results suggest EcPV2-induced VSCC undergoes EMT, potentially affecting tumor aggressiveness and metastatic potential