Expression of cyclo-oxygenases-1 and -2, and microsomal prostaglandin E synthase-1 in penile and preputial papillomas and squamous cell carcinomas in the horse.
Authors: van den Top J G B, Harkema L, Ensink J M, Barneveld A, Martens A, van de Lest C H A, van Weeren P R, Gröne A
Journal: Equine veterinary journal
Summary
# Editorial Summary: COX and mPGES-1 Expression in Equine Penile and Preputial Tumours Penile and preputial papillomas in horses carry concerning malignant potential, yet the biological mechanisms driving progression to squamous cell carcinoma remain poorly understood. Van den Top and colleagues investigated expression of three key enzymes in the arachidonic acid inflammatory pathway—COX-1, COX-2, and microsomal prostaglandin E synthase-1 (mPGES-1)—across normal tissue, papillomas, and SCCs using immunohistochemistry on 75 archived samples from 68 horses. Whilst inflammation was significantly more pronounced in SCCs than benign papillomas, COX-1 and COX-2 expression proved surprisingly sparse, detected in less than 1% of cells in the majority of lesions (59.4% and 84.2% respectively); mPGES-1 showed substantially higher expression at 96% of lesions, though correlation with inflammation was weak. These findings suggest that conventional cyclooxygenase inhibitors would likely offer limited therapeutic or preventive benefit in managing these tumours, whilst mPGES-1's prominent expression in well-differentiated tissue warrants further investigation as a potential treatment target. For practitioners managing horses with penile or preputial lesions, this research redirects focus away from systemic COX inhibition toward alternative pathways in carcinogenesis, pending development of evidence-based preventive and therapeutic strategies.
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Practical Takeaways
- •COX inhibitor therapy is unlikely to be effective for treating or preventing penile/preputial squamous cell carcinoma in horses due to minimal COX enzyme expression in these tumors
- •mPGES-1 shows promise as a potential therapeutic target and warrants further investigation into its role in equine penile and preputial carcinogenesis
- •Understanding enzyme expression patterns in these tumors may help guide development of alternative prevention and treatment strategies
Key Findings
- •mPGES-1 was expressed in 96.0% of lesions compared to COX-1 (42.6%) and COX-2 (50.7%), but COX-1 and COX-2 showed minimal immunopositive cells in 59.4% and 84.2% of cases respectively
- •COX-1 expression was moderately negatively correlated with differentiation grade, while mPGES-1 was poorly negatively correlated and COX-2 showed no correlation
- •mPGES-1 expression showed weak correlation with inflammation degree, while COX-1 and COX-2 showed no correlation
- •Poor expression of COX-1 and COX-2 in equine penile and preputial squamous cell carcinoma suggests limited therapeutic potential for COX inhibitors in prevention or treatment