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Title: Molecular carcinogenesis in equine penile cancer: A potential animal model for human penile cancer
Authors: Suárez-Bonnet, Alejandro 
Willis, Claire
Pittaway, Rachel
Smith, Ken
Mair, Tim
Priestnall, Simon L.
UNESCO Clasification: 3109 Ciencias veterinarias
Keywords: Animal model
Epithelial–mesenchymal transition
Invasion front
Penile cancer
Issue Date: 2018
Journal: Urologic Oncology: Seminars and Original Investigations 
Abstract: Objectives To evaluate the expression of COX-2, E-cadherin, vimentin, 14-3-3σ, and Phosphatase and tensin homolog (PTEN) tumor-related proteins in equine penile papillomas (ePP) and squamous cell carcinomas (ePSCC), the occurrence of epithelial-mesenchymal transition (EMT) at the invasion front (IF) and compare our findings with current knowledge on human penile squamous cell carcinoma (hPSCC). Material and methods We analyzed, by immunohistochemistry in 45 equine penile proliferative epithelial lesions, the expression of COX-2, E-cadherin, vimentin, 14-3-3σ, and PTEN using monoclonal antibodies. Tumors were histopathologically classified as well-differentiated or poorly differentiated using the IF grading scheme. Semiquantitative analysis was performed to determine down or up-regulation of the proteins and association with histopathological characteristics were statistically investigated using Mann–Whitney U test and/or Spearman's tests. Results COX-2 was neo-expressed in 86.6% of the cases and expression progressively increased from ePP to ePSCC (P = 0.0003) and from well to poorly differentiated (P = 0.033). High COX-2 expression was associated with a high mitotic index (MI) (P = 0.026). In contrast to normal epidermis, ePSCC had very low E-cadherin expression in 64% of the cases (P = 0.0005). Vimentin was neo-expressed in 65% of poorly differentiated ePSCC at the IF indicating EMT. Cytoplasmic 14-3-3σ protein expression was reduced in 42% of the ePSCC and additionally, nuclear expression of 14-3-3σ in neoplastic keratinocytes and in the cytoplasm of stromal fibroblasts at the IF was features only found in ePSCC. PTEN protein showed a tendency to be decreased or lost in ePSCC. Conclusions Our study provides evidence of molecular abnormalities in ePSCC similar to those reported for human PSCC. The occurrence of EMT at the IF is a common event in ePSCC. Naturally occurring ePSCC could serve as a valuable preclinical animal model to explore upcoming therapeutic options for hPSCC.
ISSN: 1078-1439
DOI: 10.1016/j.urolonc.2018.09.004
Source: Urologic Oncology: Seminars and Original Investigations [ISSN 1078-1439], v. 36 (12), p. 532.e9-532.e18
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