Hierarchical evaluation of histology and p16-labeling can improve the risk assessment on cervical intraepithelial neoplasia progression

Medeiros, Fernanda; Gomes, Fabiana Oliveira dos Santos; Paiva, Larissa Albuquerque; Silva, Neila Caroline Henrique da; Silva, Mauro César da; Rygaard, Maria Carolina Valença; Peixoto, Christina Alves; Welkovic, Stefan; Menezes, Maria Luiza Bezerra; Cokan, Andrej; Diniz, George Tadeu Nunes; Donadi, Eduardo Antônio; Lucena‐Silva, Norma

doi:10.1016/j.yexmp.2021.104734

Cited by 2 publications

(2 citation statements)

References 31 publications

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“…Strong immunostaining for p16 was also observed in coincidental malignant skin lesions, such as BISC, squamous cell carcinoma, and basal cell carcinoma, whereas p16 immunoreactivity was variable in viral plaques [ 61 ]. Variation in p16 immunoreactivity has been associated with the grading of HPV-associated cervical intraepithelial neoplasia in human, with increased staining in higher grades [ 93 ]. Results of our study suggest that p16 immunohistochemistry is useful for detecting papillomavirus involvement in MCC and coincidental proliferative skin lesions in the cat.…”

Section: Merkel Cell Carcinoma In Catsmentioning

confidence: 99%

Feline papillomavirus-associated Merkel cell carcinoma: a comparative review with human Merkel cell carcinoma

CHAMBERS,

ITO,

UCHIDA

2023

The Journal of Veterinary Medical Science

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Merkel cell carcinoma (MCC) is a rare skin tumor that shares a similar immunophenotype with Merkel cells, although its origin is debatable. More than 80% of human MCC cases are associated with Merkel cell polyomavirus infections and viral gene integration. Recent studies have shown that the clinical and pathological characteristics of feline MCC are comparable to those of human MCC, including its occurrence in aged individuals, aggressive behavior, histopathological findings, and the expression of Merkel cell markers. More than 90% of feline MCC are positive for the Felis catus papillomavirus type 2 (FcaPV2) gene. Molecular changes involved in papillomavirus-associated tumorigenesis, such as increased p16 and decreased retinoblastoma (Rb) and p53 protein levels, were observed in FcaPV2-positive MCC, but not in FcaPV2-negative MCC cases. These features were also confirmed in FcaPV2-positive and -negative MCC cell lines. The expression of papillomavirus E6 and E7 genes, responsible for p53 degradation and Rb inhibition, respectively, was detected in tumor cells by in situ hybridization. Whole genome sequencing revealed the integration of FcaPV2 DNA into the host feline genome. MCC cases often develop concurrent skin lesions, such as viral plaque and squamous cell carcinoma, which are also associated with papillomavirus infection. These findings suggest that FcaPV2 infection and integration of viral genes are involved in the development of MCC in cats. This review provides an overview of the comparative pathology of feline and human MCC caused by different viruses and discusses their cell of origin.

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Section: Merkel Cell Carcinoma In Catsmentioning

confidence: 99%

Feline papillomavirus-associated Merkel cell carcinoma: a comparative review with human Merkel cell carcinoma

CHAMBERS,

ITO,

UCHIDA

2023

The Journal of Veterinary Medical Science

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“…Genomic DNA was extracted from cervical samples according to the methodology reported by Medeiros et al (2022) (Medeiros et al, 2022). PCR amplification of the viral L1 gene confirmed the HPV infection, and the sequence of the L1 fragment defined the HPV type.…”

Section: Sample Processing and Characterizationmentioning

confidence: 99%

The antigen processing-associated transporter gene polymorphism: Role on gene and protein expression in HPV-infected pre-cancerous cervical lesion

Medeiros

Silva

et al. 2022

Front. Cell. Infect. Microbiol.

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Human papillomavirus (HPV) is the major pathogen for cervical lesions. The evasion mechanism of the immune response and persistence of HPV infection can be influenced by polymorphisms (SNPs) in genes associated with transporter associated with antigen processing (TAP), which may change the peptide binding affinity or the TAP expression impacting the efficiency of peptide transport in the secretory pathway, and the presentation of peptides to cytotoxic T lymphocytes. This study aimed to evaluate the role of the TAP1 and TAP2 polymorphisms, TAP1, and TAP2 genes expressions, and protein levels in cervical cells presenting different degrees of pre-cancerous lesions in 296 immunocompetent women infected or not by HPV. TAP SNPs were genotyped by Sanger sequencing, and gene expression by real-time PCR. Aneuploidy was determined by DNA index using flow cytometry. TAP-1 and TAP-2 tissue expressions were evaluated by immunohistochemistry. The Asp697Gly SNP of TAP1 presented a risk for cellular aneuploidy (P=0.0244). HPV+ women had higher TAP-2 mRNA (P=0.0212) and protein (P<0.0001) levels. The TAP2D and TAP2E haplotypes were associated with the risk for aneuploidy and pre-cancerous lesions. In conclusion, nucleotide variability at the peptide binding region of peptide transporter genes, particularly of the TAP2 gene, may influence the HPV-peptide transportation from the cytosol to the endoplasmic reticulum, increasing the susceptibility to the development of high-grade cervical lesions.

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Hierarchical evaluation of histology and p16-labeling can improve the risk assessment on cervical intraepithelial neoplasia progression

Cited by 2 publications

References 31 publications

Feline papillomavirus-associated Merkel cell carcinoma: a comparative review with human Merkel cell carcinoma

Feline papillomavirus-associated Merkel cell carcinoma: a comparative review with human Merkel cell carcinoma

The antigen processing-associated transporter gene polymorphism: Role on gene and protein expression in HPV-infected pre-cancerous cervical lesion

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