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.
Abstract: Penile and preputial papilloma and squamous cell carcinoma (SCC) are commonly diagnosed in horses. Papillomas have the potential to progress to potentially lethal SCC. Knowledge of pathogenetic mechanisms may help in prevention and definition of treatment targets. Methods: Retrospective study using archived material. Objective: To determine the expression of cyclo-oxygenase 1 (COX-1), cyclo-oxygenase 2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) in penile and preputial normal tissue, papilloma and SCC in horses, and whether expression of these enzymes is influenced by degree of inflammation and differentiation grade. Methods: Tumour differentiation grade, degree of inflammation and COX-1, COX-2 and mPGES-1 expression in 75 formalin-fixed paraffin embedded samples of penile and preputial papilloma and SCC of 68 horses were investigated by histopathology and immunohistochemistry. Results: Inflammation was more prominent in SCC compared with papilloma. No correlation between expression of COX-1 or COX-2 and inflammation was found. Expression of mPGES-1 was weakly correlated with inflammation. Expression of COX-1, COX-2 and mPGES-1 was found in 42.6%, 50.7% and 96.0% of lesions respectively, but less than 1% of cells were immunopositive for COX-1 and COX-2 in 59.4% and 84.2% of cases respectively. Expression of COX-1 was moderately negatively correlated with differentiation grade, COX-2 was not correlated and mPGES-1 was poorly negatively correlated. Conclusions: Expression of COX-1 and COX-2 in penile and preputial SCC in the horse is poor and COX inhibitors may thus be of little value for prevention or treatment. Microsomal PGES-1 is more prominently expressed in well-differentiated tissue compared with poorly differentiated tissue. Further research on the role of mPGES-1 in carcinogenesis is needed to assess its potential use as a treatment target. Knowledge of arachidonic pathway enzyme expression and their role in equine penile and preputial carcinogenesis may help in developing preventive and therapeutic strategies.
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This study examines the expression of specific enzymes in horse penile and preputial papillomas and carcinomas, and determines that these enzymes may have little value for prevention or treatment, but holds potential for further research in cancer treatment strategies.
Research Background and Objectives
The research focuses on papillomas and squamous cell carcinoma (SCC), both common diagnoses in horses.
The potential for papillomas to turn into more dangerous SCCs has sparked interest in understanding the pathogenic mechanisms behind this progression, in hopes of finding preventive measures and treatment targets.
For this goal, the study focuses on determining the expression (how large a role the enzyme plays) of cyclo-oxygenase 1 (COX-1), cyclo-oxygenase 2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1) in normal tissue, papillomas, and SCCs in horses.
The researchers also aim to understand if inflammation and tumor differentiation grades influence the expression of these enzymes.
Methods and Results
Using formalin-fixed paraffin embedded samples from 68 horses, the researchers examined tumor differentiation grade, inflammation degree, and the expression of the aforementioned enzymes by histopathology and immunohistochemistry.
Inflammation was more pronounced in SCCs compared to papillomas, but it did not appear correlated with the expression of COX-1 or COX-2.
mPGES-1 expression was weakly correlated with inflammation.
Expression of COX-1, COX-2, and mPGES-1 were found in a significant portion of lesions. However, very few cells were immunopositive (indicative of the enzymes’ presence) for COX-1 and COX-2.
COX-1 expression was moderately negatively correlated with tumor differentiation; that is, the lesser the expression of COX-1, the more differentiated the tumor was. Conversely, there was no correlation between COX-2 expression and tumor differentiation. mPGES-1 expression showed a weak negative correlation with tumor differentiation.
Conclusions and Future Implications
The study concluded that there is poor expression of COX-1 and COX-2 in the horse penile and preputial SCCs, indicating these enzymes may not be of much value as treatment targets.
mPGES-1 was found to be more prominently expressed in well-differentiated tissue than in poorly-differentiated tissue, suggesting further research into the enzyme’s role in carcinogenesis could be valuable.
The findings contribute to the existing knowledge of the arachidonic pathway enzyme expression and may advance the development of preventive and therapeutic strategies for equine penile and preputial carcinogenesis.
Cite This Article
APA
van den Top JG, Harkema L, Ensink JM, Barneveld A, Martens A, van de Lest CH, van Weeren PR, Gröne A.
(2013).
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.
Equine Vet J, 46(5), 618-624.
https://doi.org/10.1111/evj.12144
Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
Harkema, L
Ensink, J M
Barneveld, A
Martens, A
van de Lest, C H A
van Weeren, P R
Gröne, A
MeSH Terms
Animals
Carcinoma, Squamous Cell / enzymology
Carcinoma, Squamous Cell / genetics
Carcinoma, Squamous Cell / metabolism
Carcinoma, Squamous Cell / veterinary
Cyclooxygenase 1 / genetics
Cyclooxygenase 1 / metabolism
Cyclooxygenase 2 / genetics
Cyclooxygenase 2 / metabolism
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Genital Neoplasms, Male / enzymology
Genital Neoplasms, Male / genetics
Genital Neoplasms, Male / metabolism
Genital Neoplasms, Male / veterinary
Horse Diseases / metabolism
Horses
Inflammation
Intramolecular Oxidoreductases / genetics
Intramolecular Oxidoreductases / metabolism
Male
Microsomes / metabolism
Prostaglandin-E Synthases
Citations
This article has been cited 2 times.
Nasry WHS, Martin CK. Intersecting Mechanisms of Hypoxia and Prostaglandin E2-Mediated Inflammation in the Comparative Biology of Oral Squamous Cell Carcinoma. Front Oncol 2021;11:539361.