title: 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: BACKGROUND
  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.
authors.affiliation: Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
authors.forename: J G B
authors.initials: JG
authors.lastname: van den Top
authors.forename: L
authors.initials: L
authors.lastname: Harkema
authors.forename: J M
authors.initials: JM
authors.lastname: Ensink
authors.forename: A
authors.initials: A
authors.lastname: Barneveld
authors.forename: A
authors.initials: A
authors.lastname: Martens
authors.forename: C H A
authors.initials: CH
authors.lastname: van de Lest
authors.forename: P R
authors.initials: PR
authors.lastname: van Weeren
authors.forename: A
authors.initials: A
authors.lastname: Gröne
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005834:Genital Neoplasms, Male / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D006734:Horse Diseases / Q000378:metabolism*; D006736:Horses; D007249:Inflammation; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D000071876:Prostaglandin-E Synthases
chemical_list: D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases
keywords: cyclo-oxygenase; differentiation grade; horse; immunohistochemistry; microsomal prostaglandin E synthase-1; penis; squamous cell carcinoma