Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions.
Benign hyperplasia
Carcinoma in situ (CIS)
Equine papillomavirus type 2 (EcPV2)
Immunohistochemistry
Papilloma
RNA-scope
Squamous cell carcinoma (SCC)
Journal
BMC veterinary research
ISSN: 1746-6148
Titre abrégé: BMC Vet Res
Pays: England
ID NLM: 101249759
Informations de publication
Date de publication:
22 Oct 2019
22 Oct 2019
Historique:
received:
01
07
2019
accepted:
16
09
2019
entrez:
24
10
2019
pubmed:
24
10
2019
medline:
18
2
2020
Statut:
epublish
Résumé
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. 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. 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.
Sections du résumé
BACKGROUND
BACKGROUND
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
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.
CONCLUSION
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.
Identifiants
pubmed: 31640696
doi: 10.1186/s12917-019-2097-0
pii: 10.1186/s12917-019-2097-0
pmc: PMC6805557
doi:
Substances chimiques
DNA, Viral
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
356Références
J Gen Virol. 1999 Sep;80 ( Pt 9):2437-43
pubmed: 10501499
Cancer Res. 2003 Dec 1;63(23):8173-80
pubmed: 14678972
Ann Surg Oncol. 2019 Oct;26(10):3124-3132
pubmed: 31342393
J Equine Vet Sci. 2019 Jan;72:97-100
pubmed: 30929791
Mod Pathol. 2015 Jul;28(7):977-93
pubmed: 25953390
Vet Microbiol. 2012 Jul 6;158(1-2):33-41
pubmed: 22397936
Vet Pathol. 2013 Jul;50(4):686-92
pubmed: 23064881
Mol Cell Biol. 1998 Jul;18(7):4385-90
pubmed: 9632822
Equine Vet J. 2008 Sep;40(6):528-32
pubmed: 18487101
Vet Dermatol. 2011 Dec;22(6):570-4
pubmed: 21645140
Domest Anim Endocrinol. 2011 Nov;41(4):207-13
pubmed: 21982272
Am J Surg Pathol. 2011 Apr;35(4):553-62
pubmed: 21399489
Vet J. 2017 May;223:48-54
pubmed: 28671071
Equine Vet J. 1991 Jan;23(1):53-8
pubmed: 2015809
J Cancer. 2018 Apr 6;9(8):1518-1526
pubmed: 29721062
Vet J. 2014 Nov;202(2):279-85
pubmed: 25439440
Equine Vet J. 2008 Sep;40(6):533-7
pubmed: 18487102
Vet Pathol. 2015 Nov;52(6):1067-72
pubmed: 25967135
Am J Surg Pathol. 2017 May;41(5):607-615
pubmed: 28403015
Virology. 2015 Dec;486:284-90
pubmed: 26519597
Vet Comp Oncol. 2018 Dec;16(4):535-543
pubmed: 29989314
Vet Dermatol. 2018 Feb;29(1):72-e30
pubmed: 28833761
Clin Genitourin Cancer. 2016 Aug;14(4):346-51
pubmed: 26794389
Equine Vet J. 2010 Nov;42(8):738-45
pubmed: 21039805
Semin Diagn Pathol. 2012 May;29(2):72-82
pubmed: 22641956
Arch Pathol Lab Med. 2012 Oct;136(10):1266-97
pubmed: 22742517
J Clin Pathol. 2012 Jun;65(6):534-7
pubmed: 22447920
Equine Vet J. 2015 Mar;47(2):188-95
pubmed: 24898479
PLoS One. 2014 Mar 13;9(3):e91142
pubmed: 24625757
Vet Pathol. 2011 Nov;48(6):1190-4
pubmed: 21282669
Int J Infect Dis. 2019 Jan;78:148-154
pubmed: 30423461
Oncotarget. 2016 Oct 4;7(40):64910-64920
pubmed: 27626311
Vet J. 2017 Jul;225:3-8
pubmed: 28720295
J Gen Virol. 2013 Jun;94(Pt 6):1365-72
pubmed: 23486670
Hum Pathol. 2012 Jul;43(7):1020-7
pubmed: 22169255
J Gen Virol. 2019 Jun;100(6):985-998
pubmed: 31084699
J Clin Pathol. 2004 Oct;57(10):1057-62
pubmed: 15452160
Clinics (Sao Paulo). 2018 Sep 06;73(suppl 1):e551s
pubmed: 30208169
Vet Microbiol. 2011 Apr 21;149(1-2):85-90
pubmed: 21109367
Virology. 2009 Feb 20;384(2):260-5
pubmed: 19135222
Am J Surg Pathol. 2009 Jul;33(7):1042-8
pubmed: 19384189
FASEB J. 1999 May;13(8):781-92
pubmed: 10224222
Vet Dermatol. 2014 Jun;25(3):210-e54
pubmed: 24840327
Urol Oncol. 2018 Dec;36(12):532.e9-532.e18
pubmed: 30270026
Cancer Res. 2003 Nov 1;63(21):7515-9
pubmed: 14612553
Mol Med Rep. 2015 Mar;11(3):1566-72
pubmed: 25384676
Vet Comp Oncol. 2019 Sep;17(3):211-220
pubmed: 30719836
J Mol Diagn. 2012 Jan;14(1):22-9
pubmed: 22166544
Pathol Res Pract. 2017 Jul;213(7):723-729
pubmed: 28554769
Virology. 2010 Jan 5;396(1):143-51
pubmed: 19896685
Cancer Med. 2015 Jan;4(1):75-83
pubmed: 25354498
Equine Vet J. 2019 Jul;51(4):470-474
pubmed: 30456819
Transbound Emerg Dis. 2012 Oct;59(5):441-7
pubmed: 22225995
Ann Clin Lab Sci. 2003 Winter;33(1):101-6
pubmed: 12661905
Cancer Res. 2007 Feb 15;67(4):1626-35
pubmed: 17308103
J Clin Pathol. 2016 Mar;69(3):255-9
pubmed: 26420767