{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:43:41Z","timestamp":1787240621426,"version":"build-2736575974"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T00:00:00Z","timestamp":1571702400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T00:00:00Z","timestamp":1571702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Forschungskredit, University of Zurich"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Vet Res"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12917-019-2097-0","type":"journal-article","created":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T00:28:23Z","timestamp":1571790503000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions"],"prefix":"10.1186","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4741-3972","authenticated-orcid":false,"given":"Anna Sophie","family":"Ramsauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garrett Louis","family":"Wachoski-Dark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornel","family":"Fraefel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Tobler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Brandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron Greig","family":"Knight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Favrot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Grest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,22]]},"reference":[{"key":"2097_CR1","unstructured":"Campo MS: Introduction. In: Papillomavirus Research: From Natural History to Vaccines and Beyond. Edited by Campo MS, 1 edn. Norfolk, UK: Caister Academic Press; 2006: 1\u20132."},{"issue":"2","key":"2097_CR2","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.virol.2008.11.046","volume":"384","author":"H zur Hausen","year":"2009","unstructured":"zur Hausen H. Papillomaviruses in the causation of human cancers - a brief historical account. Virology. 2009;384(2):260\u20135.","journal-title":"Virology"},{"issue":"8","key":"2097_CR3","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1111\/j.2042-3306.2010.00311.x","volume":"42","author":"T Scase","year":"2010","unstructured":"Scase T, Brandt S, Kainzbauer C, Sykora S, Bijmholt S, Hughes K, Sharpe S, Foote A. Equus caballus papillomavirus-2 (EcPV-2): an infectious cause for equine genital cancer? Equine Vet J. 2010;42(8):738\u201345.","journal-title":"Equine Vet J"},{"key":"2097_CR4","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.tvjl.2017.05.007","volume":"223","author":"S Sykora","year":"2017","unstructured":"Sykora S, Brandt S. Papillomavirus infection and squamous cell carcinoma in horses. Vet J. 2017;223:48\u201354.","journal-title":"Vet J"},{"key":"2097_CR5","unstructured":"Scott DW, Miller, W. H. Jr. : Squamous cell carcinoma. In: Equine Dermatology. Edited by Scott DW, Miller, W. H. Jr. , vol. 1, 1 edn. St. Louis, Missouri, USA: Saunders Elsevier; 2003: 707\u2013712."},{"issue":"6","key":"2097_CR6","doi-asserted-by":"publisher","first-page":"528","DOI":"10.2746\/042516408X281180","volume":"40","author":"JG van den Top","year":"2008","unstructured":"van den Top JG, de Heer N, Klein WR, Ensink JM. Penile and preputial tumours in the horse: a retrospective study of 114 affected horses. Equine Vet J. 2008;40(6):528\u201332.","journal-title":"Equine Vet J"},{"key":"2097_CR7","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.tvjl.2017.04.014","volume":"225","author":"S Sykora","year":"2017","unstructured":"Sykora S, Jindra C, Hofer M, Steinborn R, Brandt S. Equine papillomavirus type 2: An equine equivalent to human papillomavirus 16? Vet J. 2017;225:3\u20138.","journal-title":"Vet J"},{"issue":"6","key":"2097_CR8","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1099\/jgv.0.001267","volume":"100","author":"AS Ramsauer","year":"2019","unstructured":"Ramsauer AS, Kubacki J, Favrot C, Ackermann M, Fraefel C, Tobler K. RNA-seq analysis in equine papillomavirus type 2-positive carcinomas identifies affected pathways and potential cancer markers as well as viral gene expression and splicing events. J Gen Virol. 2019;100(6):985\u201398.","journal-title":"J Gen Virol"},{"issue":"7","key":"2097_CR9","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1016\/j.humpath.2011.07.025","volume":"43","author":"A Chaux","year":"2012","unstructured":"Chaux A, Velazquez EF, Amin A, Soskin A, Pfannl R, Rodriguez IM, Barreto JE, Lezcano C, Ayala G, Netto GJ, et al. Distribution and characterization of subtypes of penile intraepithelial neoplasia and their association with invasive carcinomas: a pathological study of 139 lesions in 121 patients. Hum Pathol. 2012;43(7):1020\u20137.","journal-title":"Hum Pathol"},{"issue":"12","key":"2097_CR10","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1111\/j.2042-3292.2010.00216.x","volume":"23","author":"JGB Van den Top","year":"2011","unstructured":"Van den Top JGB, Ensink JM, Barneveld A, van Weeren PR. Penile and preputial squamous cell carcinoma in the horse and proposal of a classification system. Equine Vet Educ. 2011;23(12):636\u201348.","journal-title":"Equine Vet Educ"},{"issue":"2","key":"2097_CR11","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1053\/j.semdp.2011.08.002","volume":"29","author":"A Chaux","year":"2012","unstructured":"Chaux A, Cubilla AL. Diagnostic problems in precancerous lesions and invasive carcinomas of the penis. Semin Diagn Pathol. 2012;29(2):72\u201382.","journal-title":"Semin Diagn Pathol"},{"issue":"3","key":"2097_CR12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091142","volume":"9","author":"MF Evans","year":"2014","unstructured":"Evans MF, Peng Z, Clark KM, Adamson CS, Ma XJ, Wu X, Wang H, Luo Y, Cooper K. HPV E6\/E7 RNA in situ hybridization signal patterns as biomarkers of three-tier cervical intraepithelial neoplasia grade. PLoS One. 2014;9(3):e91142.","journal-title":"PLoS One"},{"issue":"7","key":"2097_CR13","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.prp.2017.03.003","volume":"213","author":"DC Silva","year":"2017","unstructured":"Silva DC, Goncalves AK, Cobucci RN, Mendonca RC, Lima PH, Cavalcanti GJ. Immunohistochemical expression of p16, Ki-67 and p53 in cervical lesions - a systematic review. Pathol Res Pract. 2017;213(7):723\u20139.","journal-title":"Pathol Res Pract"},{"issue":"7","key":"2097_CR14","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1038\/modpathol.2015.52","volume":"28","author":"H Griffin","year":"2015","unstructured":"Griffin H, Soneji Y, Van Baars R, Arora R, Jenkins D, van de Sandt M, Wu Z, Quint W, Jach R, Okon K, et al. Stratification of HPV-induced cervical pathology using the virally encoded molecular marker E4 in combination with p16 or MCM. Mod Pathol. 2015;28(7):977\u201393.","journal-title":"Mod Pathol"},{"issue":"8","key":"2097_CR15","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1096\/fasebj.13.8.781","volume":"13","author":"J Westermarck","year":"1999","unstructured":"Westermarck J, Kahari VM. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J. 1999;13(8):781\u201392.","journal-title":"FASEB J"},{"key":"2097_CR16","doi-asserted-by":"crossref","unstructured":"Herbster S, Paladino A, de Freitas S, Boccardo E: Alterations in the expression and activity of extracellular matrix components in HPV-associated infections and diseases. Clinics (Sao Paulo) 2018, 73(suppl 1):e551s.","DOI":"10.6061\/clinics\/2018\/e551s"},{"issue":"2","key":"2097_CR17","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.tvjl.2014.07.026","volume":"202","author":"S Mosseri","year":"2014","unstructured":"Mosseri S, Hetzel U, Hahn S, Michaloupoulou E, Sallabank HC, Knottenbelt DC, Kipar A. Equine sarcoid: in situ demonstration of matrix metalloproteinase expression. Vet J. 2014;202(2):279\u201385.","journal-title":"Vet J"},{"issue":"1","key":"2097_CR18","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.virol.2009.10.010","volume":"396","author":"Z Yuan","year":"2010","unstructured":"Yuan Z, Gobeil PA, Campo MS, Nasir L. Equine sarcoid fibroblasts over-express matrix metalloproteinases and are invasive. Virology. 2010;396(1):143\u201351.","journal-title":"Virology"},{"key":"2097_CR19","doi-asserted-by":"crossref","unstructured":"Schmidt F, Brodesser D, Reifinger M, Forte S, Semp P, Eberspacher-Schweda MC, Wolschek M, Brandt S, Kleiter M, Pratscher B. Canine oral primary melanoma cells exhibit shift to mesenchymal phenotype and phagocytic behaviour. Vet Comp Oncol. 2019.","DOI":"10.1111\/vco.12464"},{"issue":"2","key":"2097_CR20","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1111\/evj.12245","volume":"47","author":"JG van den Top","year":"2015","unstructured":"van den Top JG, Harkema L, Lange C, Ensink JM, van de Lest CH, Barneveld A, van Weeren PR, Grone A, Martens A. 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. 2015;47(2):188\u201395.","journal-title":"Equine Vet J"},{"issue":"1","key":"2097_CR21","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1111\/j.2042-3306.1991.tb02715.x","volume":"23","author":"S Howarth","year":"1991","unstructured":"Howarth S, Lucke VM, Pearson H. Squamous cell carcinoma of the equine external genitalia: a review and assessment of penile amputation and urethrostomy as a surgical treatment. Equine Vet J. 1991;23(1):53\u20138.","journal-title":"Equine Vet J"},{"issue":"1\u20132","key":"2097_CR22","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.vetmic.2012.02.005","volume":"158","author":"L Bogaert","year":"2012","unstructured":"Bogaert L, Willemsen A, Vanderstraeten E, Bracho MA, De Baere C, Bravo IG, Martens A. EcPV2 DNA in equine genital squamous cell carcinomas and normal genital mucosa. Vet Microbiol. 2012;158(1\u20132):33\u201341.","journal-title":"Vet Microbiol"},{"issue":"6","key":"2097_CR23","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1177\/0300985810396516","volume":"48","author":"CG Knight","year":"2011","unstructured":"Knight CG, Munday JS, Peters J, Dunowska M. Equine penile squamous cell carcinomas are associated with the presence of equine papillomavirus type 2 DNA sequences. Vet Pathol. 2011;48(6):1190\u20134.","journal-title":"Vet Pathol"},{"issue":"4","key":"2097_CR24","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1177\/0300985812463403","volume":"50","author":"CE Lange","year":"2013","unstructured":"Lange CE, Tobler K, Lehner A, Grest P, Welle MM, Schwarzwald CC, Favrot C. EcPV2 DNA in equine papillomas and in situ and invasive squamous cell carcinomas supports papillomavirus etiology. Vet Pathol. 2013;50(4):686\u201392.","journal-title":"Vet Pathol"},{"issue":"1","key":"2097_CR25","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1111\/eve.12476","volume":"29","author":"VHL Scott","year":"2017","unstructured":"Scott VHL, Hughes K. Diagnosis of equine penile and preputial masses: a clinical and pathological perspective. Equine Vet Educ. 2017;29(1):10\u20134.","journal-title":"Equine Vet Educ"},{"issue":"12","key":"2097_CR26","doi-asserted-by":"publisher","first-page":"532 e539","DOI":"10.1016\/j.urolonc.2018.09.004","volume":"36","author":"A Suarez-Bonnet","year":"2018","unstructured":"Suarez-Bonnet A, Willis C, Pittaway R, Smith K, Mair T, Priestnall SL. Molecular carcinogenesis in equine penile cancer: A potential animal model for human penile cancer. Urol Oncol. 2018;36(12):532 e539\u201318.","journal-title":"Urol Oncol"},{"issue":"6","key":"2097_CR27","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1111\/j.1365-3164.2011.00987.x","volume":"22","author":"CG Knight","year":"2011","unstructured":"Knight CG, Munday JS, Rosa BV, Kiupel M. Persistent, widespread papilloma formation on the penis of a horse: a novel presentation of equine papillomavirus type 2 infection. Vet Dermatol. 2011;22(6):570\u20134.","journal-title":"Vet Dermatol"},{"issue":"6","key":"2097_CR28","doi-asserted-by":"publisher","first-page":"533","DOI":"10.2746\/042516408X281171","volume":"40","author":"JG van den Top","year":"2008","unstructured":"van den Top JG, de Heer N, Klein WR, Ensink JM. Penile and preputial squamous cell carcinoma in the horse: a retrospective study of treatment of 77 affected horses. Equine Vet J. 2008;40(6):533\u20137.","journal-title":"Equine Vet J"},{"issue":"10","key":"2097_CR29","doi-asserted-by":"publisher","first-page":"3124","DOI":"10.1245\/s10434-019-07556-9","volume":"26","author":"CD Champion","year":"2019","unstructured":"Champion CD, Ren Y, Thomas SM, Fayanju OM, Rosenberger LH, Greenup RA, Menendez CS, Hwang ES, Plichta JK. DCIS with microinvasion: is it in situ or invasive disease? Ann Surg Oncol. 2019;26(10):3124\u201332.","journal-title":"Ann Surg Oncol"},{"issue":"10","key":"2097_CR30","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.5858\/arpa.LGT200570","volume":"136","author":"TM Darragh","year":"2012","unstructured":"Darragh TM, Colgan TJ, Cox JT, Heller DS, Henry MR, Luff RD, McCalmont T, Nayar R, Palefsky JM, Stoler MH, et al. The lower Anogenital squamous terminology standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Arch Pathol Lab Med. 2012;136(10):1266\u201397.","journal-title":"Arch Pathol Lab Med"},{"issue":"7","key":"2097_CR31","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1097\/PAS.0b013e31819aa4c9","volume":"33","author":"A Chaux","year":"2009","unstructured":"Chaux A, Torres J, Pfannl R, Barreto J, Rodriguez I, Velazquez EF, Cubilla AL. Histologic grade in penile squamous cell carcinoma: visual estimation versus digital measurement of proportions of grades, adverse prognosis with any proportion of grade 3 and correlation of a Gleason-like system with nodal metastasis. Am J Surg Pathol. 2009;33(7):1042\u20138.","journal-title":"Am J Surg Pathol"},{"issue":"1\u20132","key":"2097_CR32","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.vetmic.2010.10.019","volume":"149","author":"CE Lange","year":"2011","unstructured":"Lange CE, Tobler K, Ackermann M, Favrot C. Identification of two novel equine papillomavirus sequences suggests three genera in one cluster. Vet Microbiol. 2011;149(1\u20132):85\u201390.","journal-title":"Vet Microbiol"},{"issue":"Pt 6","key":"2097_CR33","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1099\/vir.0.052092-0","volume":"94","author":"CE Lange","year":"2013","unstructured":"Lange CE, Vetsch E, Ackermann M, Favrot C, Tobler K. Four novel papillomavirus sequences support a broad diversity among equine papillomaviruses. J Gen Virol. 2013;94(Pt 6):1365\u201372.","journal-title":"J Gen Virol"},{"issue":"4","key":"2097_CR34","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1111\/evj.13046","volume":"51","author":"J Peters-Kennedy","year":"2019","unstructured":"Peters-Kennedy J, Lange CE, Rine SL, Hackett RP. Equus caballus papillomavirus 8 (EcPV8) associated with multiple viral plaques, viral papillomas, and squamous cell carcinoma in a horse. Equine Vet J. 2019;51(4):470\u20134.","journal-title":"Equine Vet J"},{"issue":"21","key":"2097_CR35","first-page":"7515","volume":"63","author":"A Iftner","year":"2003","unstructured":"Iftner A, Klug SJ, Garbe C, Blum A, Stancu A, Wilczynski SP, Iftner T. The prevalence of human papillomavirus genotypes in nonmelanoma skin cancers of nonimmunosuppressed individuals identifies high-risk genital types as possible risk factors. Cancer Res. 2003;63(21):7515\u20139.","journal-title":"Cancer Res"},{"issue":"Pt 9","key":"2097_CR36","doi-asserted-by":"publisher","first-page":"2437","DOI":"10.1099\/0022-1317-80-9-2437","volume":"80","author":"O Forslund","year":"1999","unstructured":"Forslund O, Antonsson A, Nordin P, Stenquist B, Hansson BG. A broad range of human papillomavirus types detected with a general PCR method suitable for analysis of cutaneous tumours and normal skin. J Gen Virol. 1999;80(Pt 9):2437\u201343.","journal-title":"J Gen Virol"},{"issue":"1","key":"2097_CR37","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1111\/vde.12481","volume":"29","author":"KE Linder","year":"2018","unstructured":"Linder KE, Bizikova P, Luff J, Zhou D, Yuan H, Breuhaus B, Nelson E, Mackay R. Generalized papillomatosis in three horses associated with a novel equine papillomavirus (EcPV8). Vet Dermatol. 2018;29(1):72\u2013e30.","journal-title":"Vet Dermatol"},{"issue":"5","key":"2097_CR38","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1111\/j.1865-1682.2011.01296.x","volume":"59","author":"CC Carvalho","year":"2012","unstructured":"Carvalho CC, Batista MV, Silva MA, Balbino VQ, Freitas AC. Detection of bovine papillomavirus types, co-infection and a putative new BPV11 subtype in cattle. Transbound Emerg Dis. 2012;59(5):441\u20137.","journal-title":"Transbound Emerg Dis"},{"issue":"1","key":"2097_CR39","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.jmoldx.2011.08.002","volume":"14","author":"F Wang","year":"2012","unstructured":"Wang F, Flanagan J, Su N, Wang LC, Bui S, Nielson A, Wu XY, Vo HT, Ma XJ, Luo YL. RNAscope a novel in situ RNA analysis platform for formalin-fixed, Paraffin-Embedded Tissues. J Mol Diagnostics. 2012;14(1):22\u20139.","journal-title":"J Mol Diagnostics"},{"issue":"5","key":"2097_CR40","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1097\/PAS.0000000000000800","volume":"41","author":"AM Mills","year":"2017","unstructured":"Mills AM, Dirks DC, Poulter MD, Mills SE, Stoler MH. HR-HPV E6\/E7 mRNA in situ hybridization validation against PCR, DNA in situ hybridization, and p16 immunohistochemistry in 102 samples of cervical, vulvar, anal, and head and neck Neoplasia. Am J Surg Pathol. 2017;41(5):607\u201315.","journal-title":"Am J Surg Pathol"},{"issue":"6","key":"2097_CR41","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1177\/0300985815583095","volume":"52","author":"KW Zhu","year":"2015","unstructured":"Zhu KW, Affolter VK, Gaynor AM, Dela Cruz FN Jr, Pesavento PA. Equine genital squamous cell carcinoma: in situ hybridization identifies a distinct subset containing Equus caballus papillomavirus 2. Vet Pathol. 2015;52(6):1067\u201372.","journal-title":"Vet Pathol"},{"issue":"3","key":"2097_CR42","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1111\/vde.12129","volume":"25","author":"NM Fischer","year":"2014","unstructured":"Fischer NM, Favrot C, Birkmann K, Jackson M, Schwarzwald CC, Muller M, Tobler K, Geisseler M, Lange CE. Serum antibodies and DNA indicate a high prevalence of equine papillomavirus 2 (EcPV2) among horses in Switzerland. Vet Dermatol. 2014;25(3):210\u20134 e253-214.","journal-title":"Vet Dermatol"},{"key":"2097_CR43","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.jevs.2018.10.015","volume":"72","author":"SK Lee","year":"2019","unstructured":"Lee SK, Lee JK, Lee I. Molecular detection of Equus caballus papillomavirus type 2 in genital swabs from healthy horses in the Republic of Korea. J Equine Vet Sci. 2019;72:97\u2013100.","journal-title":"J Equine Vet Sci"},{"key":"2097_CR44","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.virol.2015.08.016","volume":"486","author":"C Schellenbacher","year":"2015","unstructured":"Schellenbacher C, Shafti-Keramat S, Huber B, Fink D, Brandt S, Kirnbauer R. Establishment of an in vitro equine papillomavirus type 2 (EcPV2) neutralization assay and a VLP-based vaccine for protection of equids against EcPV2-associated genital tumors. Virology. 2015;486:284\u201390.","journal-title":"Virology"},{"issue":"7","key":"2097_CR45","doi-asserted-by":"publisher","first-page":"4385","DOI":"10.1128\/MCB.18.7.4385","volume":"18","author":"Y Xu","year":"1998","unstructured":"Xu Y, Yang EM, Brugarolas J, Jacks T, Baltimore D. Involvement of p53 and p21 in cellular defects and tumorigenesis in Atm(\u2212\/\u2212) mice. Mol Cell Biol. 1998;18(7):4385\u201390.","journal-title":"Mol Cell Biol"},{"issue":"1","key":"2097_CR46","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1002\/cam4.346","volume":"4","author":"K Ando","year":"2015","unstructured":"Ando K, Oki E, Saeki H, Yan Z, Tsuda Y, Hidaka G, Kasagi Y, Otsu H, Kawano H, Kitao H, et al. Discrimination of p53 immunohistochemistry-positive tumors by its staining pattern in gastric cancer. Cancer Med. 2015;4(1):75\u201383.","journal-title":"Cancer Med"},{"issue":"40","key":"2097_CR47","doi-asserted-by":"publisher","first-page":"64910","DOI":"10.18632\/oncotarget.11912","volume":"7","author":"B Murnyak","year":"2016","unstructured":"Murnyak B, Hortobagyi T. Immunohistochemical correlates of TP53 somatic mutations in cancer. Oncotarget. 2016;7(40):64910\u201320.","journal-title":"Oncotarget"},{"issue":"1","key":"2097_CR48","first-page":"101","volume":"33","author":"A Ouban","year":"2003","unstructured":"Ouban A, Dellis J, Salup R, Morgan M. Immunohistochemical expression of Mdm2 and p53 in penile verrucous carcinoma. Ann Clin Lab Sci. 2003;33(1):101\u20136.","journal-title":"Ann Clin Lab Sci"},{"key":"2097_CR49","first-page":"184a","volume":"91","author":"A Chaux","year":"2011","unstructured":"Chaux A, Pfannl R, Rodriguez IM, Barreto JE, Velazquez EF, Netto GJ, Cubilla AL. Distinctive Immunohistochemical Profiles of Penile Intraepithelial Lesions - A Study of 74 Cases. Lab Investigation. 2011;91:184a.","journal-title":"Lab Investigation"},{"issue":"4","key":"2097_CR50","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.clgc.2015.12.019","volume":"14","author":"Kamran Zargar-Shoshtari","year":"2016","unstructured":"Zargar-Shoshtari K, Spiess PE, Berglund AE, Sharma P, Powsang JM, GiulianoA,\u00a0Magliocco AM, Dhillon J. Clinical Significance of p53 and p16ink4a Status in a Contemporary North American Penile Carcinoma Cohort. Clinical Genitourinary Cancer. 2016;14(4):346\u201351.\u00a0\n                    https:\/\/doi.org\/10.1016\/j.clgc.2015.12.019\n                    \n                  .","journal-title":"Clinical Genitourinary Cancer"},{"issue":"3","key":"2097_CR51","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.3892\/mmr.2014.2914","volume":"11","author":"LT Li","year":"2015","unstructured":"Li LT, Jiang G, Chen Q, Zheng JN. Ki67 is a promising molecular target in the diagnosis of cancer. Mol Med Rep. 2015;11(3):1566\u201372.","journal-title":"Mol Med Rep"},{"issue":"6","key":"2097_CR52","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1136\/jclinpath-2011-200638","volume":"65","author":"E Stankiewicz","year":"2012","unstructured":"Stankiewicz E, Ng M, Cuzick J, Mesher D, Watkin N, Lam W, Corbishley C, Berney DM. The prognostic value of Ki-67 expression in penile squamous cell carcinoma. J Clin Pathol. 2012;65(6):534\u20137.","journal-title":"J Clin Pathol"},{"issue":"3","key":"2097_CR53","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1136\/jclinpath-2015-203174","volume":"69","author":"N Arima","year":"2016","unstructured":"Arima N, Nishimura R, Osako T, Nishiyama Y, Fujisue M, Okumura Y, Nakano M, Tashima R, Toyozumi Y. The importance of tissue handling of surgically removed breast cancer for an accurate assessment of the Ki-67 index. J Clin Pathol. 2016;69(3):255\u20139.","journal-title":"J Clin Pathol"},{"issue":"4","key":"2097_CR54","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1111\/vco.12412","volume":"16","author":"D Berlato","year":"2018","unstructured":"Berlato D, Murphy S, Laberke S, Rasotto R. Comparison of minichromosome maintenance protein 7, Ki67 and mitotic index in the prognosis of intermediate Patnaik grade cutaneous mast cell tumours in dogs. Vet Comp Oncol. 2018;16(4):535\u201343.","journal-title":"Vet Comp Oncol"},{"issue":"4","key":"2097_CR55","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.domaniend.2011.07.002","volume":"41","author":"H Ishino","year":"2011","unstructured":"Ishino H, Hara Y, Takekoshi S, Teshima T, Teramoto A, Osamura RY, Tagawa M. Ki-67 and minichromosome maintenance-7 (MCM7) expression in canine pituitary corticotroph adenomas. Domest Anim Endocrinol. 2011;41(4):207\u201313.","journal-title":"Domest Anim Endocrinol"},{"issue":"10","key":"2097_CR56","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1136\/jcp.2004.016436","volume":"57","author":"V Padmanabhan","year":"2004","unstructured":"Padmanabhan V, Callas P, Philips G, Trainer TD, Beatty BG. DNA replication regulation protein Mcm7 as a marker of proliferation in prostate cancer. J Clin Pathol. 2004;57(10):1057\u201362.","journal-title":"J Clin Pathol"},{"issue":"8","key":"2097_CR57","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.7150\/jca.22691","volume":"9","author":"KH Gou","year":"2018","unstructured":"Gou KH, Liu JW, Feng X, Li H, Yuan Y, Xing CZ. Expression of Minichromosome maintenance proteins (MCM) and Cancer prognosis: a meta-analysis. J Cancer. 2018;9(8):1518\u201326.","journal-title":"J Cancer"},{"issue":"23","key":"2097_CR58","first-page":"8173","volume":"63","author":"T Brake","year":"2003","unstructured":"Brake T, Connor JP, Petereit DG, Lambert PF. Comparative analysis of cervical cancer in women and in a human papillomavirus-transgenic mouse model: identification of Minichromosome maintenance protein 7 as an informative biomarker for human cervical cancer. Cancer Res. 2003;63(23):8173\u201380.","journal-title":"Cancer Res"},{"issue":"7","key":"2097_CR59","first-page":"3492","volume":"67","author":"A Shai","year":"2007","unstructured":"Shai A, Brake T, Somoza C, Lambert PF. The human papillomavirus E6 oncogene dysregulates the cell cycle and contributes to cervical carcinogenesis through two independent activities (vol 67, pg 1626, 2007). Cancer Res. 2007;67(7):3492.","journal-title":"Cancer Res"},{"key":"2097_CR60","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.ijid.2018.11.003","volume":"78","author":"J Sakamoto","year":"2019","unstructured":"Sakamoto J, Shigehara K, Nakashima K, Kawaguchi S, Nakashima T, Shimamura M, Yasuda M, Kato T, Hasegawa T, Kobori Y, et al. Etiological role of human papillomavirus infection in the development of penile cancer. Int J Infect Dis. 2019;78:148\u201354.","journal-title":"Int J Infect Dis"}],"container-title":["BMC Veterinary Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-019-2097-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12917-019-2097-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-019-2097-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T19:17:13Z","timestamp":1603221433000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcvetres.biomedcentral.com\/articles\/10.1186\/s12917-019-2097-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,22]]},"references-count":60,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["2097"],"URL":"https:\/\/doi.org\/10.1186\/s12917-019-2097-0","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.2.11540\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.2.11540\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.2.11540\/v3","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.2.11540\/v4","asserted-by":"object"}]},"ISSN":["1746-6148"],"issn-type":[{"value":"1746-6148","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,22]]},"assertion":[{"value":"1 July 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study did not involve experimental animals. It was a retrospective study on horse sample material derived from FFPE tissue, which was analysed for diagnostic purposes at the Institutes for Pathology, Vetsuisse Faculty, University of Zurich and Bern.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"356"}}