Comparison of minichromosome maintenance protein 7, Ki67 and mitotic index in the prognosis of intermediate Patnaik grade cutaneous mast cell tumours in dogs

Berlato, Davide; Murphy, Sue; Laberke, S.; Rasotto, Roberta

doi:10.1111/vco.12412

“…This is also supported by another study using this antibody in equine penile and preputial SCCs whereby they could also not find expression differences between different subtypes [20]. The proliferation marker MCM7 is more sensitive in detecting cycling cells than Ki67 in humans and dogs and therefor might be superior to Ki67 as a proliferation marker [54][55][56].…”

Section: Ihc-based Marker Gene Expression In Different Lesionssupporting

confidence: 54%

Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions

Ramsauer

¹

,

Wachoski-Dark

²

,

Fraefel

³

et al. 2019

Preprint

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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 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 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.

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“…This is also supported by another study using this antibody in equine penile and preputial SCCs whereby they could also not find expression differences between different subtypes [20]. The proliferation marker MCM7 is more sensitive in detecting cycling cells than Ki67 in humans and dogs and therefor might be superior to Ki67 as a proliferation marker [54–56].…”

Section: Discussionmentioning

confidence: 57%

Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions

Ramsauer

¹

,

Wachoski-Dark

²

,

Fraefel

³

et al. 2019

View full text Add to dashboard Cite

BackgroundThere 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.ResultsA 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.ConclusionThis 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.

show abstract

“…This is also supported by another study using this antibody in equine penile and preputial SCCs whereby they could also not find expression differences between different subtypes [20]. The proliferation marker MCM7 is more sensitive in detecting cycling cells than ki67 in humans and dogs and therefor might be superior to ki67 as a proliferation marker [54][55][56].…”

Section: Ihc-based Marker Gene Expression In Different Lesionssupporting

confidence: 52%

Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions

Ramsauer

¹

,

Wachoski-Dark

²

,

Fraefel

³

et al. 2019

Preprint

0

View full text Add to dashboard Cite

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 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 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.

show abstract

Comparison of minichromosome maintenance protein 7, Ki67 and mitotic index in the prognosis of intermediate Patnaik grade cutaneous mast cell tumours in dogs

Cited by 15 publications

References 19 publications

Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions

Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions

Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions

Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions

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