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BMC veterinary research2019; 15(1); 356; doi: 10.1186/s12917-019-2097-0

Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions.

Abstract: There is growing evidence that equine papillomavirus type 2 (EcPV2) infection is causally associated with the development of equine genital squamous cell carcinomas (SCCs). Early stages of disease present clinically as plaques or wart-like lesions which can gradually progress to tumoural lesions. Histologically these lesions are inconsistently described as benign hyperplasia, papilloma, penile intraepithelial neoplasia (PIN), carcinoma in situ (CIS) or SCC. Guidelines for histological classification of early SCC precursor lesions are not precisely defined, leading to potential misdiagnosis. The aim of this study was to identify histologic criteria and diagnostic markers allowing for a more accurate diagnosis of EcPV2-associated equine penile lesions. Results: A total of 61 archived equine penile lesions were histologically re-assessed and classified as benign hyperplasia, papilloma, CIS or SCC. From these, 19 representative lesions and adjacent normal skin were comparatively analysed for the presence of EcPV2 DNA and transcripts using PCR and RNA in situ hybridisation (RISH). All lesional samples were positive by EcPV2 PCR and RISH, while adjacent normal skin was negative. RISH analysis yielded signal distribution patterns that allowed distinction of early (hyperplasia, papilloma) from late stage lesions (CIS, SCC). Subsequently, the 19 lesions were further assessed for expression of p53, Ki67, MCM7 and MMP1 by immunohistochemistry (IHC). All four proteins were expressed in both normal and lesional tissue. However, p53 expression was up-regulated in basal keratinocyte layers of papillomas, CIS and SCCs, as well as in upper keratinocyte layers of CIS and SCCs. MCM7 expression was only up-regulated in upper proliferating keratinocyte layers of papillomas, CIS and SCCs. Conclusions: This study proposes combining a refined histological protocol for analysis of equine penile lesions with PCR- and/or RISH based EcPV2-screening and p53/MCM7 IHC to more accurately determine the type of lesion. This may help to guide the choice of optimum treatment strategy, especially at early stages of disease.
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Publication Date: 2019-10-22 PubMed ID: 31640696PubMed Central: PMC6805557DOI: 10.1186/s12917-019-2097-0Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The article discusses a study aimed at improving diagnosis of EcPV2-related equine penile lesions by identifying precise histological criteria and diagnostic markers. The team studied 61 archived equine penile lesions, re-assessed their classifications and analysed chosen samples for the presence of EcPV2 DNA. The results suggest that combining a refined analysis with EcPV2-screening and p53/MCM7 immunohistochemistry could lead to more accurate disease identification and subsequently, more effective treatment, particularly in the early stages of the disease.

Study Focus and Rationale

  • This research focuses on equine papillomavirus type 2 (EcPV2) infection, which has been increasingly linked to the development of equine genital squamous cell carcinomas (SCCs).
  • These SCCs often start as plaques or wart-like lesions, but can progress into tumors. The histological descriptions of these lesions vary, often referred to as hyperplasia, papilloma, penile intraepithelial neoplasia (PIN), carcinoma in situ (CIS) or SCC.
  • The inconsistency in description and lack of precise guidelines for histological classification can potentially lead to misdiagnoses. This study ventures to identify the histological and diagnostic markers that can better diagnose equine penile lesions associated with EcPV2.

Research Conduct and Findings

  • A total of 61 archived equine penile lesion samples were re-assessed and classified. From these, 19 representative lesions and adjacent normal skin were analysed comparatively for the presence of EcPV2 DNA using PCR and RNA in situ hybridization (RISH).
  • All the lesion samples tested positive for EcPV2 using PCR or RISH, while the normal skin samples turned out negative. Distinct patterns of signal distribution were identified that allowed the researchers to distinguish early-stage lesions (hyperplasia, papillomas) from late-stage lesions (CIS, SCC).
  • The selected 19 lesions were further examined for the expression of p53, Ki67, MCM7, and MMP1 proteins using immunohistochemistry (IHC).
  • The four proteins were expressed in both normal and lesion tissues, but peculiar patterns of expression were recognized. For instance, p53 was up-regulated in basal keratinocyte layers of papillomas, CIS and SCCs.

Conclusion

  • This study proposes a method of improving the precision of identifying equine penile lesions related to EcPV2: combining refined histological analysis with EcPV2 screening and p53/MCM7 IHC.
  • This approach can contribute significantly to advancing the accuracy of disease identification, and subsequently aid in choosing the optimal treatment strategy, especially in the early stages of the disease.

Cite This Article

APA
Ramsauer AS, Wachoski-Dark GL, Fraefel C, Tobler K, Brandt S, Knight CG, Favrot C, Grest P. (2019). Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions. BMC Vet Res, 15(1), 356. https://doi.org/10.1186/s12917-019-2097-0

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 15
Issue: 1
Pages: 356
PII: 356

Researcher Affiliations

Ramsauer, Anna Sophie
  • Institute of Virology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. sramsauer@vetclinics.uzh.ch.
  • Dermatology Department, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. sramsauer@vetclinics.uzh.ch.
Wachoski-Dark, Garrett Louis
  • Department of Veterinary Clinical and Diagnostic Sciences, Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada.
Fraefel, Cornel
  • Institute of Virology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Tobler, Kurt
  • Institute of Virology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Brandt, Sabine
  • Research Group Oncology, Equine Clinic, University of Veterinary Medicine Vienna, Vienna, Austria.
Knight, Cameron Greig
  • Department of Veterinary Clinical and Diagnostic Sciences, Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada.
Favrot, Claude
  • Dermatology Department, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Grest, Paula
  • Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.

MeSH Terms

  • Animals
  • DNA, Viral / analysis
  • Horse Diseases / pathology
  • Horse Diseases / virology
  • Horses
  • In Situ Hybridization / veterinary
  • Male
  • Papillomaviridae / classification
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / veterinary
  • Penile Neoplasms / pathology
  • Penile Neoplasms / veterinary
  • Penile Neoplasms / virology
  • Penis / pathology
  • Precancerous Conditions / pathology
  • Precancerous Conditions / veterinary
  • Precancerous Conditions / virology

Conflict of Interest Statement

The authors declare that they have no competing interests.

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Citations

This article has been cited 12 times.
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