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: 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.
© 2014 EVJ Ltd.
Publication Date: 2014-05-04 PubMed ID: 24898479DOI: 10.1111/evj.12245Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article analyzes how various characteristics of equine penile and preputial squamous cell carcinoma (SCC), including the presence of specific viral genes and proteins, and different levels of tumour differentiation, affect the likelihood of metastasis and survival. The researchers found that the level of tumour differentiation is an important predictor for survival and metastasis, but other factors like the expression of certain proteins and the presence of specific viral types had less impact.
Research Methods
- This research was a retrospective case-control study, using samples from 87 horses previously diagnosed with penile and/or preputial intraepithelial neoplasia, papilloma, or SCC.
- All tumours in the samples were graded on their differentiation subtype by microscopic examination.
- The presence and level of expression of p53 and Ki67 proteins were recorded using immunohistochemical methods.
- DNA detection of Equine papillomavirus (EcPV) types 2 and 3 was performed using conventional polymerase chain reaction (PCR).
- The quantitative expression of E2, E6, and L1 viral oncogenes was analyzed using real-time PCR.
Key Findings
- Evidence of EcPV2 was detected in a large proportion of the studied horses, while EcPV3 was found in very few horses.
- There was no significant difference in expression of E2, E6, and L1 oncogenes across the different tumour subtypes.
- Expression of p53 and presence of metastasis both increased in relation to less differentiated subtypes of tumour.
- There were significant survival differences between different tumour subtypes: lower differentiation levels corresponded with lower survival rates.
Conclusion
- The level of tumour differentiation is a key determinant of survival and metastasis probability in cases of equine penile and preputial SCC.
- Other factors including the presence or expression levels of EcPV2, EcPV3 and proteins p53 and Ki67, were not found to be significant prognosticators in this study.
Cite This Article
APA
van den Top JG, Harkema L, Lange C, Ensink JM, van de Lest CH, Barneveld A, van Weeren PR, Gröne A, Martens A.
(2014).
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.
Equine Vet J, 47(2), 188-195.
https://doi.org/10.1111/evj.12245 Publication
Researcher Affiliations
- Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
MeSH Terms
- Animals
- Carcinoma, Squamous Cell / classification
- Carcinoma, Squamous Cell / metabolism
- Carcinoma, Squamous Cell / veterinary
- Gene Expression Regulation, Neoplastic / physiology
- Gene Expression Regulation, Viral / physiology
- Genital Neoplasms, Male / metabolism
- Genital Neoplasms, Male / veterinary
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horses
- Ki-67 Antigen / genetics
- Ki-67 Antigen / metabolism
- Male
- Papillomaviridae / genetics
- Tumor Suppressor Protein p53 / genetics
- Tumor Suppressor Protein p53 / metabolism
- Viral Proteins / genetics
- Viral Proteins / metabolism
Citations
This article has been cited 8 times.- Miglinci L, Reicher P, Nell B, Koch M, Jindra C, Brandt S. Detection of Equine Papillomaviruses and Gamma-Herpesviruses in Equine Squamous Cell Carcinoma. Pathogens 2023 Jan 23;12(2).
- Mecocci S, Porcellato I, Armando F, Mechelli L, Brachelente C, Pepe M, Gialletti R, Passeri B, Modesto P, Ghelardi A, Cappelli K, Razzuoli E. Equine Genital Squamous Cell Carcinoma Associated with EcPV2 Infection: RANKL Pathway Correlated to Inflammation and Wnt Signaling Activation. Biology (Basel) 2021 Mar 21;10(3).
- Medeiros-Fonseca B, Cubilla A, Brito H, Martins T, Medeiros R, Oliveira P, Gil da Costa RM. Experimental Models for Studying HPV-Positive and HPV-Negative Penile Cancer: New Tools for An Old Disease. Cancers (Basel) 2021 Jan 26;13(3).
- Yamashita-Kawanishi N, Haga T. Anogenital-Associated Papillomaviruses in Animals: Focusing on Bos taurus Papillomaviruses. Pathogens 2020 Nov 27;9(12).
- Porcellato I, Mecocci S, Mechelli L, Cappelli K, Brachelente C, Pepe M, Orlandi M, Gialletti R, Passeri B, Ferrari A, Modesto P, Ghelardi A, Razzuoli E. Equine Penile Squamous Cell Carcinomas as a Model for Human Disease: A Preliminary Investigation on Tumor Immune Microenvironment. Cells 2020 Oct 27;9(11).
- Ramsauer AS, Wachoski-Dark GL, Fraefel C, Tobler K, Brandt S, Knight CG, Favrot C, Grest P. Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions. BMC Vet Res 2019 Oct 22;15(1):356.
- Mira J, Herman M, Zakia LS, Olivo G, Araújo JP Jr, Borges AS, Oliveira-Filho JP. Frequency of Equus caballus papillomavirus in equine aural plaques. J Vet Diagn Invest 2018 Jul;30(4):565-568.
- Munday JS, Knight CG, Luff JA. Papillomaviral skin diseases of humans, dogs, cats and horses: A comparative review. Part 2: Pre-neoplastic and neoplastic diseases. Vet J 2022 Oct;288:105898.
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