Epithelial-mesenchymal transition in an EcPV2-positive vulvar squamous cell carcinoma of a mare.

Abstract

BACKGROUND: Vulvar squamous cell carcinoma (VSCC) has been recently associated with Equus caballus papillomavirus type 2 (EcPV2) infection. Still, few reports concerning this disease are present in the literature. OBJECTIVE: To describe a case of naturally occurring EcPV2-induced VSCC, by investigating tumour ability in undergoing the epithelial-to-mesenchymal transition (EMT). STUDY DESIGN: Case report. METHODS: A 13-year-old Haflinger mare was referred for a rapidly growing vulvar mass. After surgical excision, the mass was submitted to histopathology and molecular analysis. Histopathological diagnosis was consistent with a VSCC. Real-time qPCR, real-time reverse transcriptase (RT)-qPCR and RNAscope were carried out to detect EcPV2 infection and to evaluate E6/E7 oncogenes expression. To highlight the EMT, immunohistochemistry (IHC) was performed. Expression of EMT-related and innate immunity-related genes was investigated through RT-qPCR. RESULTS: Real-time qPCR, RT-qPCR and RNAscope confirmed EcPV2 DNA presence and expression of EcPV2 oncoproteins (E6 and E7) within the neoplastic vulvar lesion. IHC highlighted a cadherin switch together with the expression of the EMT-related transcription factor HIF1&#x3b1;. With RT-qPCR, significantly increased gene expression of EBI3 (45.0&#x2009;&#xb1;&#x2009;1.62, p&#x2009;<&#x2009;0.01), CDH2 (2445.3&#x2009;&#xb1;&#x2009;0.39, p&#x2009;<&#x2009;0.001), CXCL8 (288.7&#x2009;&#xb1;&#x2009;0.40, p&#x2009;<&#x2009;0.001) and decreased gene expression of CDH1 (0.3&#x2009;&#xb1;&#x2009;0.57, p&#x2009;<&#x2009;0.05), IL12A (0.04&#x2009;&#xb1;&#x2009;1.06, p&#x2009;<&#x2009;0.01) and IL17 (0.2&#x2009;&#xb1;&#x2009;0.64, p&#x2009;<&#x2009;0.05) were detected. MAIN LIMITATIONS: Lack of ability to generalise and danger of over-interpretation. CONCLUSION: The results obtained were suggestive of an EMT event occurring within the neoplastic lesion.