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

J G B van den Top; L Harkema; C Lange; J M Ensink; C H A van de Lest; A Barneveld; P R van Weeren; A Gröne; A Martens

doi:10.1111/evj.12245

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

J G B van den Top, L Harkema, C Lange, J M Ensink, C H A van de Lest, A Barneveld, P R van Weeren, A Gröne, A Martens

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

REASONS FOR PERFORMING STUDY: Equine penile and preputial squamous cell carcinoma (SCC) is a potentially lethal disease of which little is known regarding the relationship between tumour characteristics and prognosis.

OBJECTIVES: To assess the relationship between tumour differentiation grade (tumour subtype), presence of papillomaviruses, expression of viral genes (E2, E6, L1), nuclear proteins p53 and Ki67 and metastasis in equine penile and preputial SCC and to assess the relationship of tumour subtype, presence of papillomavirus type 2, p53 and Ki67 with survival.

STUDY DESIGN: Retrospective case-control study using archived material.

METHODS: Samples (n = 103) from 87 horses with penile and/or preputial intraepithelial neoplasia (PIN), papilloma or SCC and corresponding case files were evaluated. Tumours were graded microscopically and p53 and Ki67 expression evaluated immunohistochemically. Equine papillomavirus (EcPV) types 2 and 3 DNA was detected by conventional PCR. Real-time PCR was used for quantification of E2, E6 and L1 mRNA.

RESULTS: Equine papillomavirus type 2 DNA was detected in 89.4% and EcPV3 in 1.5% of horses. No differences in quantitative expression of E2, E6 and L1 oncogenes between subtypes were found. Expression of p53 and occurrence of metastasis were positively correlated to a less differentiated subtype (r = 0.429, P<0.001 and r = 0.769, P = 0.001, respectively). Differences in survival between subtypes were significant (log Rank P<0.001); horses with less differentiated tumours were more likely to die of the disease (papilloma 8.3%; G1 26.1%; G2 26.3%; G3 63.3%).

CONCLUSIONS: In equine penile and preputial SCC, tumour grading is an important prognosticator for survival and a predictor for presence of metastases. Expression of p53 and Ki67 and presence or expression of EcPV2 and EcPV3 do not appear to be important prognosticators.

Original language	English
Pages (from-to)	188–195
Journal	Equine Veterinary Journal
Volume	47
Issue number	2
Early online date	4 May 2014
DOIs	https://doi.org/10.1111/evj.12245
Publication status	Published - Mar 2015

Keywords

horse
squamous cell carcinoma
penis
grading
p53
Ki67
EcPV2
EcPV3
immunohistochemistry

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10.1111/evj.12245

2015Final published version, 0.99 MBLicence: Taverne

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van den Top, J. G. B., Harkema, L., Lange, C., Ensink, J. M., van de Lest, C. H. A., Barneveld, A., van Weeren, P. R., Gröne, A., & Martens, A. (2015). 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 Veterinary Journal, 47(2), 188–195. https://doi.org/10.1111/evj.12245

@article{01bbed2edea24401a5c1ed26b3437a39,

title = "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",

abstract = "REASONS FOR PERFORMING STUDY: Equine penile and preputial squamous cell carcinoma (SCC) is a potentially lethal disease of which little is known regarding the relationship between tumour characteristics and prognosis.OBJECTIVES: To assess the relationship between tumour differentiation grade (tumour subtype), presence of papillomaviruses, expression of viral genes (E2, E6, L1), nuclear proteins p53 and Ki67 and metastasis in equine penile and preputial SCC and to assess the relationship of tumour subtype, presence of papillomavirus type 2, p53 and Ki67 with survival.STUDY DESIGN: Retrospective case-control study using archived material.METHODS: Samples (n = 103) from 87 horses with penile and/or preputial intraepithelial neoplasia (PIN), papilloma or SCC and corresponding case files were evaluated. Tumours were graded microscopically and p53 and Ki67 expression evaluated immunohistochemically. Equine papillomavirus (EcPV) types 2 and 3 DNA was detected by conventional PCR. Real-time PCR was used for quantification of E2, E6 and L1 mRNA.RESULTS: Equine papillomavirus type 2 DNA was detected in 89.4\% and EcPV3 in 1.5\% of horses. No differences in quantitative expression of E2, E6 and L1 oncogenes between subtypes were found. Expression of p53 and occurrence of metastasis were positively correlated to a less differentiated subtype (r = 0.429, P<0.001 and r = 0.769, P = 0.001, respectively). Differences in survival between subtypes were significant (log Rank P<0.001); horses with less differentiated tumours were more likely to die of the disease (papilloma 8.3\%; G1 26.1\%; G2 26.3\%; G3 63.3\%).CONCLUSIONS: In equine penile and preputial SCC, tumour grading is an important prognosticator for survival and a predictor for presence of metastases. Expression of p53 and Ki67 and presence or expression of EcPV2 and EcPV3 do not appear to be important prognosticators.",

keywords = "horse, squamous cell carcinoma, penis, grading, p53, Ki67, EcPV2, EcPV3, immunohistochemistry",

author = "\{van den Top\}, \{J G B\} and L Harkema and C Lange and Ensink, \{J M\} and \{van de Lest\}, \{C H A\} and A Barneveld and \{van Weeren\}, \{P R\} and A Gr{\"o}ne and A Martens",

year = "2015",

month = mar,

doi = "10.1111/evj.12245",

language = "English",

volume = "47",

pages = "188–195",

journal = "Equine Veterinary Journal",

issn = "0425-1644",

publisher = "British Equine Veterinary Association",

number = "2",

}

van den Top, JGB, Harkema, L, Lange, C, Ensink, JM , van de Lest, CHA, Barneveld, A, van Weeren, PR , Gröne, A & Martens, A 2015, '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 Veterinary Journal, vol. 47, no. 2, pp. 188–195. https://doi.org/10.1111/evj.12245

TY - JOUR

T1 - 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

AU - van den Top, J G B

AU - Harkema, L

AU - Lange, C

AU - Ensink, J M

AU - van de Lest, C H A

AU - Barneveld, A

AU - van Weeren, P R

AU - Gröne, A

AU - Martens, A

PY - 2015/3

Y1 - 2015/3

N2 - REASONS FOR PERFORMING STUDY: Equine penile and preputial squamous cell carcinoma (SCC) is a potentially lethal disease of which little is known regarding the relationship between tumour characteristics and prognosis.OBJECTIVES: To assess the relationship between tumour differentiation grade (tumour subtype), presence of papillomaviruses, expression of viral genes (E2, E6, L1), nuclear proteins p53 and Ki67 and metastasis in equine penile and preputial SCC and to assess the relationship of tumour subtype, presence of papillomavirus type 2, p53 and Ki67 with survival.STUDY DESIGN: Retrospective case-control study using archived material.METHODS: Samples (n = 103) from 87 horses with penile and/or preputial intraepithelial neoplasia (PIN), papilloma or SCC and corresponding case files were evaluated. Tumours were graded microscopically and p53 and Ki67 expression evaluated immunohistochemically. Equine papillomavirus (EcPV) types 2 and 3 DNA was detected by conventional PCR. Real-time PCR was used for quantification of E2, E6 and L1 mRNA.RESULTS: Equine papillomavirus type 2 DNA was detected in 89.4% and EcPV3 in 1.5% of horses. No differences in quantitative expression of E2, E6 and L1 oncogenes between subtypes were found. Expression of p53 and occurrence of metastasis were positively correlated to a less differentiated subtype (r = 0.429, P<0.001 and r = 0.769, P = 0.001, respectively). Differences in survival between subtypes were significant (log Rank P<0.001); horses with less differentiated tumours were more likely to die of the disease (papilloma 8.3%; G1 26.1%; G2 26.3%; G3 63.3%).CONCLUSIONS: In equine penile and preputial SCC, tumour grading is an important prognosticator for survival and a predictor for presence of metastases. Expression of p53 and Ki67 and presence or expression of EcPV2 and EcPV3 do not appear to be important prognosticators.

AB - REASONS FOR PERFORMING STUDY: Equine penile and preputial squamous cell carcinoma (SCC) is a potentially lethal disease of which little is known regarding the relationship between tumour characteristics and prognosis.OBJECTIVES: To assess the relationship between tumour differentiation grade (tumour subtype), presence of papillomaviruses, expression of viral genes (E2, E6, L1), nuclear proteins p53 and Ki67 and metastasis in equine penile and preputial SCC and to assess the relationship of tumour subtype, presence of papillomavirus type 2, p53 and Ki67 with survival.STUDY DESIGN: Retrospective case-control study using archived material.METHODS: Samples (n = 103) from 87 horses with penile and/or preputial intraepithelial neoplasia (PIN), papilloma or SCC and corresponding case files were evaluated. Tumours were graded microscopically and p53 and Ki67 expression evaluated immunohistochemically. Equine papillomavirus (EcPV) types 2 and 3 DNA was detected by conventional PCR. Real-time PCR was used for quantification of E2, E6 and L1 mRNA.RESULTS: Equine papillomavirus type 2 DNA was detected in 89.4% and EcPV3 in 1.5% of horses. No differences in quantitative expression of E2, E6 and L1 oncogenes between subtypes were found. Expression of p53 and occurrence of metastasis were positively correlated to a less differentiated subtype (r = 0.429, P<0.001 and r = 0.769, P = 0.001, respectively). Differences in survival between subtypes were significant (log Rank P<0.001); horses with less differentiated tumours were more likely to die of the disease (papilloma 8.3%; G1 26.1%; G2 26.3%; G3 63.3%).CONCLUSIONS: In equine penile and preputial SCC, tumour grading is an important prognosticator for survival and a predictor for presence of metastases. Expression of p53 and Ki67 and presence or expression of EcPV2 and EcPV3 do not appear to be important prognosticators.

KW - horse

KW - squamous cell carcinoma

KW - penis

KW - grading

KW - p53

KW - Ki67

KW - EcPV2

KW - EcPV3

KW - immunohistochemistry

U2 - 10.1111/evj.12245

DO - 10.1111/evj.12245

M3 - Article

C2 - 24898479

SN - 0425-1644

VL - 47

SP - 188

EP - 195

JO - Equine Veterinary Journal

JF - Equine Veterinary Journal

IS - 2

ER -

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

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