title: Expression of p53, Ki67, EcPV2- and EcPV3 DNA, and viral genes in relation to metastasis and outcome in equine penile and preputial squamous cell carcinoma.
abstract: BACKGROUND
  Equine penile and preputial squamous cell carcinoma (SCC) is a potentially lethal disease of which little is known regarding the relationship between tumour characteristics and prognosis.
  
  
  OBJECTIVE
  To assess the relationship between tumour differentiation grade (tumour subtype), presence of papillomaviruses, expression of viral genes (E2, E6, L1), nuclear proteins p53 and Ki67 and metastasis in equine penile and preputial SCC and to assess the relationship of tumour subtype, presence of papillomavirus type 2, p53 and Ki67 with survival.
  
  
  METHODS
  Retrospective case-control study using archived material.
  
  
  METHODS
  Samples (n = 103) from 87 horses with penile and/or preputial intraepithelial neoplasia (PIN), papilloma or SCC and corresponding case files were evaluated. Tumours were graded microscopically and p53 and Ki67 expression evaluated immunohistochemically. Equine papillomavirus (EcPV) types 2 and 3 DNA was detected by conventional PCR. Real-time PCR was used for quantification of E2, E6 and L1 mRNA.
  
  
  RESULTS
  Equine papillomavirus type 2 DNA was detected in 89.4% and EcPV3 in 1.5% of horses. No differences in quantitative expression of E2, E6 and L1 oncogenes between subtypes were found. Expression of p53 and occurrence of metastasis were positively correlated to a less differentiated subtype (r = 0.429, P<0.001 and r = 0.769, P = 0.001, respectively). Differences in survival between subtypes were significant (log Rank P<0.001); horses with less differentiated tumours were more likely to die of the disease (papilloma 8.3%; G1 26.1%; G2 26.3%; G3 63.3%).
  
  
  CONCLUSIONS
  In equine penile and preputial SCC, tumour grading is an important prognosticator for survival and a predictor for presence of metastases. Expression of p53 and Ki67 and presence or expression of EcPV2 and EcPV3 do not appear to be important prognosticators.
authors.affiliation: Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 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: C
authors.initials: C
authors.lastname: Lange
authors.forename: J M
authors.initials: JM
authors.lastname: Ensink
authors.forename: C H A
authors.initials: CH
authors.lastname: van de Lest
authors.forename: A
authors.initials: A
authors.lastname: Barneveld
authors.forename: P R
authors.initials: PR
authors.lastname: van Weeren
authors.forename: A
authors.initials: A
authors.lastname: Gröne
authors.forename: A
authors.initials: A
authors.lastname: Martens
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000145:classification / Q000378:metabolism / Q000662:veterinary*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D005834:Genital Neoplasms, Male / Q000378:metabolism / Q000662:veterinary*; D006734:Horse Diseases / Q000378:metabolism* / Q000473:pathology; D006736:Horses; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D008297:Male; D027383:Papillomaviridae / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins
keywords: EcPV2; EcPV3; Ki67; grading; horse; immunohistochemistry; p53; penis; squamous cell carcinoma