Expression of Cell-Cycle Regulatory Proteins pRb, Cyclin D1, and p53 Is Not Associated with Recurrence Rates of Equine Sarcoids

Sarcoids are among the most common tumors diagnosed in equids; their association with bovine papillomaviruses (BPV) infection has been widely reported, but the mechanism of carcinogenesis has not been fully elucidated. To verify whether BPV infection causes dysregulation of the pRb-Cyclin D1-p16<...

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Main Authors: Giorgia Tura, Barbara Brunetti, Elena Brigandì, Riccardo Rinnovati, Giuseppe Sarli, Giancarlo Avallone, Luisa Vera Muscatello, Roberto Marcello La Ragione, Andy E. Durham, Barbara Bacci
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Veterinary Sciences
Subjects:
Online Access:https://www.mdpi.com/2306-7381/9/9/474
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author Giorgia Tura
Barbara Brunetti
Elena Brigandì
Riccardo Rinnovati
Giuseppe Sarli
Giancarlo Avallone
Luisa Vera Muscatello
Roberto Marcello La Ragione
Andy E. Durham
Barbara Bacci
author_facet Giorgia Tura
Barbara Brunetti
Elena Brigandì
Riccardo Rinnovati
Giuseppe Sarli
Giancarlo Avallone
Luisa Vera Muscatello
Roberto Marcello La Ragione
Andy E. Durham
Barbara Bacci
author_sort Giorgia Tura
collection DOAJ
description Sarcoids are among the most common tumors diagnosed in equids; their association with bovine papillomaviruses (BPV) infection has been widely reported, but the mechanism of carcinogenesis has not been fully elucidated. To verify whether BPV infection causes dysregulation of the pRb-Cyclin D1-p16<sup>CDKN2A</sup>-p53 pathway as reported for human papillomavirus (HPV), the study employed immunohistochemistry to test 55 equine sarcoid biopsies for the expression of pRb, Cyclin D1, and p53 cell cycle regulatory proteins and to evaluate the proliferative rate through Ki67. High Cyclin D1 and pRb expression were observed in 51% and 80% of cases, respectively, while low expression was observed in 49% and 20% of cases, respectively. Significantly higher Ki67 proliferation indexes were observed in fibroblastic, nodular, and mixed sarcoids compared to the occult and verrucous. High proliferation was significantly associated with high Cyclin D1 expression. In contrast with previous studies, p53 positivity was not observed in the cases examined in this study. Moreover, follow-up analysis revealed that fibroblastic, mixed sarcoids were associated with significantly higher local recurrence rates while the verrucous subtype was associated with higher rates of new sarcoid development at distant sites.
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spelling doaj.art-c563433f5c62449989b1a9f783ba86142023-11-23T19:24:00ZengMDPI AGVeterinary Sciences2306-73812022-09-019947410.3390/vetsci9090474Expression of Cell-Cycle Regulatory Proteins pRb, Cyclin D1, and p53 Is Not Associated with Recurrence Rates of Equine SarcoidsGiorgia Tura0Barbara Brunetti1Elena Brigandì2Riccardo Rinnovati3Giuseppe Sarli4Giancarlo Avallone5Luisa Vera Muscatello6Roberto Marcello La Ragione7Andy E. Durham8Barbara Bacci9Department of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, ItalySchool of Veterinary Medicine and Science, University of Surrey, Guildford GU2 7XH, UKSchool of Veterinary Medicine and Science, University of Surrey, Guildford GU2 7XH, UKDepartment of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, ItalySarcoids are among the most common tumors diagnosed in equids; their association with bovine papillomaviruses (BPV) infection has been widely reported, but the mechanism of carcinogenesis has not been fully elucidated. To verify whether BPV infection causes dysregulation of the pRb-Cyclin D1-p16<sup>CDKN2A</sup>-p53 pathway as reported for human papillomavirus (HPV), the study employed immunohistochemistry to test 55 equine sarcoid biopsies for the expression of pRb, Cyclin D1, and p53 cell cycle regulatory proteins and to evaluate the proliferative rate through Ki67. High Cyclin D1 and pRb expression were observed in 51% and 80% of cases, respectively, while low expression was observed in 49% and 20% of cases, respectively. Significantly higher Ki67 proliferation indexes were observed in fibroblastic, nodular, and mixed sarcoids compared to the occult and verrucous. High proliferation was significantly associated with high Cyclin D1 expression. In contrast with previous studies, p53 positivity was not observed in the cases examined in this study. Moreover, follow-up analysis revealed that fibroblastic, mixed sarcoids were associated with significantly higher local recurrence rates while the verrucous subtype was associated with higher rates of new sarcoid development at distant sites.https://www.mdpi.com/2306-7381/9/9/474equidsarcoidbovine papillomavirusp16<sup>CDKN2A</sup>pRbCyclin D1
spellingShingle Giorgia Tura
Barbara Brunetti
Elena Brigandì
Riccardo Rinnovati
Giuseppe Sarli
Giancarlo Avallone
Luisa Vera Muscatello
Roberto Marcello La Ragione
Andy E. Durham
Barbara Bacci
Expression of Cell-Cycle Regulatory Proteins pRb, Cyclin D1, and p53 Is Not Associated with Recurrence Rates of Equine Sarcoids
Veterinary Sciences
equid
sarcoid
bovine papillomavirus
p16<sup>CDKN2A</sup>
pRb
Cyclin D1
title Expression of Cell-Cycle Regulatory Proteins pRb, Cyclin D1, and p53 Is Not Associated with Recurrence Rates of Equine Sarcoids
title_full Expression of Cell-Cycle Regulatory Proteins pRb, Cyclin D1, and p53 Is Not Associated with Recurrence Rates of Equine Sarcoids
title_fullStr Expression of Cell-Cycle Regulatory Proteins pRb, Cyclin D1, and p53 Is Not Associated with Recurrence Rates of Equine Sarcoids
title_full_unstemmed Expression of Cell-Cycle Regulatory Proteins pRb, Cyclin D1, and p53 Is Not Associated with Recurrence Rates of Equine Sarcoids
title_short Expression of Cell-Cycle Regulatory Proteins pRb, Cyclin D1, and p53 Is Not Associated with Recurrence Rates of Equine Sarcoids
title_sort expression of cell cycle regulatory proteins prb cyclin d1 and p53 is not associated with recurrence rates of equine sarcoids
topic equid
sarcoid
bovine papillomavirus
p16<sup>CDKN2A</sup>
pRb
Cyclin D1
url https://www.mdpi.com/2306-7381/9/9/474
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