Ki-67 and minichromosome maintenance-7 (MCM7) expression in canine pituitary corticotroph adenomas

Ishino, Hirokazu; Hara, Yasushi; Takekoshi, Susumu; Teshima, Teruki; Teramoto, Akira; Osamura, R. Yoshiyuki; Tagawa, Masahiro

doi:10.1016/j.domaniend.2011.07.002

“…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][55][56].…”

Section: Ihc-based Marker Gene Expression In Different Lesionssupporting

confidence: 53%

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.

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“…prostate cancer, knockdown of MCM7 dramatically reduced the tumor volumes, decreased tumor metastasis and animal mortality (32). Some reports indicated that MCM7 was a more reliable and useful biomarker in assessing tumor proliferation, aggression and in the prognosis of patients even than the existing markers such as Ki-67 (33,34). In primary diffuse-type GACs, we identified that MCM7 was moderately/strongly stained in 96 of 123 GAC (78.0%) and its overexpression was closely correlated with advanced age (>60 years).…”

Section: Discussionmentioning

confidence: 99%

MCM7 serves as a prognostic marker in diffuse-type gastric adenocarcinoma and siRNA-mediated knockdown suppresses its oncogenic function

Kang

¹

,

Tong

²

,

Chan

³

et al. 2014

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Abstract. MCM7 (mini-chromosome maintenance protein 7) is essential for the initiation of genomic replication as a component of the pre-replication complex. The present study aimed to analyze its expression, clinical significance and biological functions in gastric adenocarcinoma (GAC). The MCM7 protein was upregulated in all 9 GAC cell lines. In 6 paired primary GACs, MCM7 was upregulated in tumor compared with the corresponding non-tumorous gastric tissues. In normal gastric epithelium tissue, MCM7 was strictly expressed in the proliferative compartment. MCM7 knockdown by siRNA in gastric cancer cell line AGS and NCI-N87 significantly suppressed cell proliferation, inhibited monolayer colony formation, reduced cell invasion and induced late apoptosis. Its nuclear expression correlated with advanced age and poorer disease specific survival in diffuse-type GACs. All the findings supported that MCM7 might play an oncogenic role in gastric tumorigenesis. It serves as a potential prognostic marker and therapeutic target in diffuse-type GACs.

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Ki-67 and minichromosome maintenance-7 (MCM7) expression in canine pituitary corticotroph adenomas

Cited by 16 publications

References 27 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

MCM7 serves as a prognostic marker in diffuse-type gastric adenocarcinoma and siRNA-mediated knockdown suppresses its oncogenic function

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