Equine genital and ocular squamous cell carcinomas: clinical, histopathological, molecular and viral characterization with proposed histopathological classification system

TL;DR

This study classifies equine squamous cell carcinomas into six subtypes and explores their molecular and viral features to improve prognosis prediction.

Contribution

The first histopathological classification system for equine SCCs is proposed, with subtype-specific prognostic implications.

Findings

Six histopathological subtypes of equine SCCs were identified, with prognostic significance.

p16 expression may serve as a potential prognostic factor in eSCCs.

HER-2 expression is widespread in eSCCs and could be a therapeutic target.

Abstract

Equine squamous cell carcinomas (eSCCs) are common, and a proportion are likely induced by Equus caballus papillomavirus 2 (EcPV-2). Accurate prediction of clinical outcomes is challenging with no recognized prognostic criteria or consistent histopathological classification scheme for eSCC. The aims of this study were to histopathologically subtype a large case series of eSCCs (genital and ocular) and correlate them with p16 and HER-2 expression, equine papillomavirus infection status, and various clinical and histopathological parameters to predict tumour behavior and prognosis. One hundred and eighty-five samples were examined and subtyped histologically. HER-2 and p16 immunohistochemistry (IHC) and in situ hybridization (ISH) for the EcPV-2 E6/E7 oncogenes were performed on a subset of cases, and follow-up survival data were analyzed. The results were compared and correlated with published guidelines on the categorization of human SCC. Six histopathological subtypes of SCC, according to the WHO, were identified for the first time in horses: usual/invasive (most common), verrucous, pseudoglandular, papillary, warty, and basaloid, with different histological subtypes demonstrating prognostic significance. HER-2 and EcPV-2 statuses were not associated with prognosis in horses with SCC. p16 expression is not associated with EcPV-2 status but could be a potential prognostic factor. ISH demonstrated EcPV-2 genetic material in the majority of eSCCs, except for the papillary subtype, which includes mature, not just pre-cancerous, eSCCs. Widespread HER-2 expression in eSCCs could suggest a role for this cell receptor as a potential therapeutic target.

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