Expression of Cell-Cycle Regulatory Proteins pRb, Cyclin D1, and p53 Is Not Associated with Recurrence Rates of Equine Sarcoids.
Abstract: 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-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.
Publication Date: 2022-09-01 PubMed ID: 36136690PubMed Central: PMC9504470DOI: 10.3390/vetsci9090474Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- 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 research investigates the link between Bovine Papillomaviruses infection and the regulation of certain proteins involved in cell cycle regulation in relation to equine sarcoid tumors. It found that while the presence of certain proteins was high in some tumor subtypes, there was no observed correlation with recurrence rates.
Understanding Equine Sarcoids and Cell-Cycle Regulatory Proteins
- Sarcoids are common tumors in equids, entities including horses, donkeys, and zebras.
- These tumors have been identified as being associated with an infection from Bovine Papillomaviruses, although the exact mechanisms causing the tumors are not fully understood.
- The proteins pRb, Cyclin D1, and p53 play critical roles in regulating the cell cycle. Regularities or irregularities in their expression could impact cell division and potentially instigate tumor growth.
Methodology and Findings
- The research study involved usage of immunohistochemistry to test 55 equine sarcoid biopsy samples for the expression of the cell-cycle regulatory proteins pRb, Cyclin D1, and p53. Furthermore, proliferation rate was assessed through Ki67, another protein marker which indicates cell proliferation.
- The results showed high levels of Cyclin D1 and pRb expression in 51% and 80% of cases, respectively, and low expression in the remaining cases.
- The study also revealed higher Ki67 proliferation rates in certain types of sarcoids (fibroblastic, nodular, and mixed) relative to others (occult and verrucous).
- A significant association was noticed between high proliferation and high Cyclin D1 expression.
Interpreting Results and Implications
- Contrary to other research, the studied samples showed no positive p53 expression.
- Additional analysis highlighted that fibroblastic, mixed sarcoids had significantly higher local recurrence rates, whereas verrucous subtype had higher incidence of new sarcoid development at different locations.
- The noteworthy point, however, is that despite these findings, the expression of pRb, Cyclin D1, and p53 was not connected with the rates of recurrence, meaning the regulation of these proteins does not seem to correlate or influence the recurrence of these tumors.
Cite This Article
APA
Tura G, Brunetti B, Brigandì E, Rinnovati R, Sarli G, Avallone G, Muscatello LV, La Ragione RM, Durham AE, Bacci B.
(2022).
Expression of Cell-Cycle Regulatory Proteins pRb, Cyclin D1, and p53 Is Not Associated with Recurrence Rates of Equine Sarcoids.
Vet Sci, 9(9), 474.
https://doi.org/10.3390/vetsci9090474 Publication
Researcher Affiliations
- Department of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, Italy.
- Department of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, Italy.
- Department of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, Italy.
- Department of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, Italy.
- Department of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, Italy.
- Department of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, Italy.
- Department of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, Italy.
- School of Veterinary Medicine and Science, University of Surrey, Guildford GU2 7XH, UK.
- School of Biosciences and Medicine, University of Surrey, Guildford GU2 7XH, UK.
- School of Veterinary Medicine and Science, University of Surrey, Guildford GU2 7XH, UK.
- Liphook Equine Hospital, Liphook GU30 7JG, UK.
- Department of Veterinary Medical Sciences, University of Bologna, 40064 Bologna, Italy.
Conflict of Interest Statement
The authors declare no conflict of interest.
References
This article includes 31 references
- Knowles EJ, Tremaine WH, Pearson GR, Mair TS. A database survey of equine tumours in the United Kingdom.. Equine Vet J 2016 May;48(3):280-4.
- Schaffer PA, Wobeser B, Martin LE, Dennis MM, Duncan CG. Cutaneous neoplastic lesions of equids in the central United States and Canada: 3,351 biopsy specimens from 3,272 equids (2000-2010).. J Am Vet Med Assoc 2013 Jan 1;242(1):99-104.
- Wobeser BK, Davies JL, Hill JE, Jackson ML, Kidney BA, Mayer MN, Townsend HG, Allen AL. Epidemiology of equine sarcoids in horses in western Canada.. Can Vet J 2010 Oct;51(10):1103-8.
- Bergvall KE. Sarcoids.. Vet Clin North Am Equine Pract 2013 Dec;29(3):657-71.
- Knottenbelt D.C.. Sarcoids. In: Knottenbelt D.C., Patterson-Kane J., Snalune K.L., editors. Clinical Equine Oncology. Elsevier; Toronto, ON, Canada: 2015. pp. 203–229.
- Chambers G, Ellsmore VA, O'Brien PM, Reid SWJ, Love S, Campo MS, Nasir L. Association of bovine papillomavirus with the equine sarcoid.. J Gen Virol 2003 May;84(Pt 5):1055-1062.
- Finlay M, Yuan Z, Morgan IM, Campo MS, Nasir L. Equine sarcoids: Bovine Papillomavirus type 1 transformed fibroblasts are sensitive to cisplatin and UVB induced apoptosis and show aberrant expression of p53.. Vet Res 2012 Dec 4;43(1):81.
- Schafer KA. The cell cycle: a review.. Vet Pathol 1998 Nov;35(6):461-78.
- Altamura G, Corteggio A, Nasir L, Yuan ZQ, Roperto F, Borzacchiello G. Analysis of activated platelet-derived growth factor β receptor and Ras-MAP kinase pathway in equine sarcoid fibroblasts.. Biomed Res Int 2013;2013:283985.
- Borzacchiello G, Mogavero S, De Vita G, Roperto S, Della Salda L, Roperto F. Activated platelet-derived growth factor beta receptor expression, PI3K-AKT pathway molecular analysis, and transforming signals in equine sarcoids.. Vet Pathol 2009 Jul;46(4):589-97.
- Nasir L, Mcfarlane ST, Reid SW. Mutational status of the tumour suppressor gene (p53) in donkey sarcoid tumours.. Vet J 1999 Jan;157(1):99-101.
- Bucher K, Szalai G, Marti E, Griot-Wenk ME, Lazary S, Pauli U. Tumour suppressor gene p53 in the horse: identification, cloning, sequencing and a possible role in the pathogenesis of equine sarcoid.. Res Vet Sci 1996 Sep;61(2):114-9.
- Martens A, De Moor A, Demeulemeester J, Ducatelle R. Histopathological characteristics of five clinical types of equine sarcoid.. Res Vet Sci 2000 Dec;69(3):295-300.
- Nixon C, Chambers G, Ellsmore V, Campo MS, Burr P, Argyle DJ, Reid SW, Nasir L. Expression of cell cycle associated proteins cyclin A, CDK-2, p27kip1 and p53 in equine sarcoids.. Cancer Lett 2005 Apr 28;221(2):237-45.
- Tomita Y, Ogawa T, Jin Z, Shirasawa H. Genus specific features of bovine papillomavirus E6, E7, E5 and E8 proteins.. Virus Res 2007 Mar;124(1-2):231-6.
- Narechania A, Terai M, Chen Z, DeSalle R, Burk RD. Lack of the canonical pRB-binding domain in the E7 ORF of artiodactyl papillomaviruses is associated with the development of fibropapillomas.. J Gen Virol 2004 May;85(Pt 5):1243-1250.
- Tura G, Savini F, Gallina L, La Ragione RM, Durham AE, Mazzeschi M, Lauriola M, Avallone G, Sarli G, Brunetti B, Muscatello LV, Girone C, Bacci B. Fibroblast-associated protein-α expression and BPV nucleic acid distribution in equine sarcoids.. Vet Pathol 2021 Nov;58(6):1044-1050.
- Gavressea T, Kalogeras KT, Koliou GA, Zagouri F, Lazaridis G, Gogas H, Tsigaridas K, Koutras A, Petraki K, Markopoulos C, Pazarli E, Aravantinos G, Papadimitriou C, Papakostas P, Koufopoulos N, Karanikiotis C, Chrisafi S, Kalofonos HP, Pectasides D, Fountzilas G, Pavlakis K. The Prognostic Value of the Immunohistochemical Expression of Phosphorylated RB and p16 Proteins in Association with Cyclin D1 and the p53 Pathway in a Large Cohort of Patients with Breast Cancer Treated with Taxane-based Adjuvant Chemotherapy.. Anticancer Res 2017 Jun;37(6):2947-2957.
- Kusume T, Tsuda H, Kawabata M, Inoue T, Umesaki N, Suzuki T, Yamamoto K. The p16-cyclin D1/CDK4-pRb pathway and clinical outcome in epithelial ovarian cancer.. Clin Cancer Res 1999 Dec;5(12):4152-7.
- Nicolás I, Saco A, Barnadas E, Marimon L, Rakislova N, Fusté P, Rovirosa A, Gaba L, Buñesch L, Gil-Ibañez B, Pahisa J, Díaz-Feijoo B, Torne A, Ordi J, Del Pino M. Prognostic implications of genotyping and p16 immunostaining in HPV-positive tumors of the uterine cervix.. Mod Pathol 2020 Jan;33(1):128-137.
- Karpathiou G, Monaya A, Forest F, Froudarakis M, Casteillo F, Marc Dumollard J, Prades JM, Peoc'h M. p16 and p53 expression status in head and neck squamous cell carcinoma: a correlation with histological, histoprognostic and clinical parameters.. Pathology 2016 Jun;48(4):341-8.
- Jiromaru R, Yamamoto H, Yasumatsu R, Hongo T, Nozaki Y, Nakano T, Hashimoto K, Nakagawa T, Oda Y. p16 overexpression and Rb loss correlate with high-risk HPV infection in oropharyngeal squamous cell carcinoma.. Histopathology 2021 Sep;79(3):358-369.
- Zhao W, Huang CC, Otterson GA, Leon ME, Tang Y, Shilo K, Villalona MA. Altered p16(INK4) and RB1 Expressions Are Associated with Poor Prognosis in Patients with Nonsmall Cell Lung Cancer.. J Oncol 2012;2012:957437.
- Plath M, Broglie MA, Förbs D, Stoeckli SJ, Jochum W. Prognostic significance of cell cycle-associated proteins p16, pRB, cyclin D1 and p53 in resected oropharyngeal carcinoma.. J Otolaryngol Head Neck Surg 2018 Sep 6;47(1):53.
- Collard TJ, Urban BC, Patsos HA, Hague A, Townsend PA, Paraskeva C, Williams AC. The retinoblastoma protein (Rb) as an anti-apoptotic factor: expression of Rb is required for the anti-apoptotic function of BAG-1 protein in colorectal tumour cells.. Cell Death Dis 2012 Oct 11;3(10):e408.
- Lu JW, Lin YM, Chang JG, Yeh KT, Chen RM, Tsai JJ, Su WW, Hu RM. Clinical implications of deregulated CDK4 and Cyclin D1 expression in patients with human hepatocellular carcinoma.. Med Oncol 2013 Mar;30(1):379.
- Cheng G, Zhang L, Lv W, Dong C, Wang Y, Zhang J. Overexpression of cyclin D1 in meningioma is associated with malignancy grade and causes abnormalities in apoptosis, invasion and cell cycle progression.. Med Oncol 2015 Jan;32(1):439.
- Song JY, Song L, Herrera AF, Venkataraman G, Murata-Collins JL, Bedell VH, Chen YY, Kim YS, Tadros R, Nathwani BN, Weisenburger DD, Feldman AL. Cyclin D1 expression in peripheral T-cell lymphomas.. Mod Pathol 2016 Nov;29(11):1306-1312.
- Zamboni C, Brocca G, Ferraresso S, Ferro S, Sammarco A, Dal Corso C, Iussich S, de Andres PJ, Martìnez de Merlo EM, Cavicchioli L, Zappulli V, Castagnaro M. Cyclin D1 immunohistochemical expression and somatic mutations in canine oral melanoma.. Vet Comp Oncol 2020 Jun;18(2):231-238.
- Araldi RP, Mazzuchelli-de-Souza J, Modolo DG, de Souza EB, de Melo TC, Spadacci-Morena DD, Magnelli RF, de Carvalho MA, de Sá Júnior PL, de Carvalho RF, Beçak W, Stocco Rde C. Mutagenic Potential ofBos taurus Papillomavirus Type 1 E6 Recombinant Protein: First Description.. Biomed Res Int 2015;2015:806361.
- Haspeslagh M, Vlaminck LE, Martens AM. Treatment of sarcoids in equids: 230 cases (2008-2013).. J Am Vet Med Assoc 2016 Aug 1;249(3):311-8.
Citations
This article has been cited 1 times.- Karalus W, Subharat S, Orbell G, Vaatstra B, Munday JS. Equine sarcoids: A clinicopathologic study of 49 cases, with mitotic count and clinical type predictive of recurrence. Vet Pathol 2024 May;61(3):357-365.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
