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DNA methylation markers for cancer risk prediction of vulvar intraepithelial neoplasia

Current clinical and histological classifications are unable to determine the risk of vulvar squamous cell carcinoma (VSCC) in high‐grade vulvar intraepithelial neoplasia (VIN), making prognostic biomarkers highly needed. We studied host‐cell DNA methylation markers in high‐grade squamous intraepith...

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Autores principales: Thuijs, Nikki B., Berkhof, Johannes, Özer, Müjde, Duin, Sylvia, van Splunter, Annina P., Snoek, Barbara C., Heideman, Daniëlle A. M., van Beurden, Marc, Steenbergen, Renske D. M., Bleeker, Maaike C. G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048962/
https://www.ncbi.nlm.nih.gov/pubmed/33426639
http://dx.doi.org/10.1002/ijc.33459
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author Thuijs, Nikki B.
Berkhof, Johannes
Özer, Müjde
Duin, Sylvia
van Splunter, Annina P.
Snoek, Barbara C.
Heideman, Daniëlle A. M.
van Beurden, Marc
Steenbergen, Renske D. M.
Bleeker, Maaike C. G.
author_facet Thuijs, Nikki B.
Berkhof, Johannes
Özer, Müjde
Duin, Sylvia
van Splunter, Annina P.
Snoek, Barbara C.
Heideman, Daniëlle A. M.
van Beurden, Marc
Steenbergen, Renske D. M.
Bleeker, Maaike C. G.
author_sort Thuijs, Nikki B.
collection PubMed
description Current clinical and histological classifications are unable to determine the risk of vulvar squamous cell carcinoma (VSCC) in high‐grade vulvar intraepithelial neoplasia (VIN), making prognostic biomarkers highly needed. We studied host‐cell DNA methylation markers in high‐grade squamous intraepithelial lesion (HSIL) and differentiated VIN (dVIN) without VSCC, in HSIL and dVIN adjacent to VSCC and in human papillomavirus (HPV) positive and negative VSCC, relative to control vulvar tissues. A series of 192 formalin‐fixed paraffin‐embedded vulvar samples, including VSCC (n = 58), VIN adjacent to VSCC (n = 30), VIN without VSCC during follow‐up (n = 41) and normal vulvar tissues (n = 63), were tested for 12 DNA methylation markers with quantitative multiplex methylation‐specific PCR (qMSP). HPV status was determined by p16(INK4A) immunohistochemistry and high‐risk HPV PCR analysis. Logistic regression analyses were used to determine methylation patterns and methylation marker performance for VIN and VSCC detection. Methylation markers showed significantly higher methylation levels with increasing severity of disease. VIN adjacent to VSCC showed a similar methylation‐high pattern as VSCC, while VIN without VSCC displayed a heterogeneous methylation pattern. Vulvar carcinogenesis is associated with increased DNA methylation. Higher DNA methylation levels in VIN seem to reflect higher cancer risk, emphasizing the high potential of DNA methylation biomarkers in the diagnostic workup of VIN. As a next step, longitudinal studies are needed to verify the prognostic value of methylation biomarkers as a clinical tool for stratification of cancer risk in women with VIN.
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spelling pubmed-80489622021-04-20 DNA methylation markers for cancer risk prediction of vulvar intraepithelial neoplasia Thuijs, Nikki B. Berkhof, Johannes Özer, Müjde Duin, Sylvia van Splunter, Annina P. Snoek, Barbara C. Heideman, Daniëlle A. M. van Beurden, Marc Steenbergen, Renske D. M. Bleeker, Maaike C. G. Int J Cancer Cancer Genetics and Epigenetics Current clinical and histological classifications are unable to determine the risk of vulvar squamous cell carcinoma (VSCC) in high‐grade vulvar intraepithelial neoplasia (VIN), making prognostic biomarkers highly needed. We studied host‐cell DNA methylation markers in high‐grade squamous intraepithelial lesion (HSIL) and differentiated VIN (dVIN) without VSCC, in HSIL and dVIN adjacent to VSCC and in human papillomavirus (HPV) positive and negative VSCC, relative to control vulvar tissues. A series of 192 formalin‐fixed paraffin‐embedded vulvar samples, including VSCC (n = 58), VIN adjacent to VSCC (n = 30), VIN without VSCC during follow‐up (n = 41) and normal vulvar tissues (n = 63), were tested for 12 DNA methylation markers with quantitative multiplex methylation‐specific PCR (qMSP). HPV status was determined by p16(INK4A) immunohistochemistry and high‐risk HPV PCR analysis. Logistic regression analyses were used to determine methylation patterns and methylation marker performance for VIN and VSCC detection. Methylation markers showed significantly higher methylation levels with increasing severity of disease. VIN adjacent to VSCC showed a similar methylation‐high pattern as VSCC, while VIN without VSCC displayed a heterogeneous methylation pattern. Vulvar carcinogenesis is associated with increased DNA methylation. Higher DNA methylation levels in VIN seem to reflect higher cancer risk, emphasizing the high potential of DNA methylation biomarkers in the diagnostic workup of VIN. As a next step, longitudinal studies are needed to verify the prognostic value of methylation biomarkers as a clinical tool for stratification of cancer risk in women with VIN. John Wiley & Sons, Inc. 2021-01-19 2021-05-15 /pmc/articles/PMC8048962/ /pubmed/33426639 http://dx.doi.org/10.1002/ijc.33459 Text en © 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Genetics and Epigenetics
Thuijs, Nikki B.
Berkhof, Johannes
Özer, Müjde
Duin, Sylvia
van Splunter, Annina P.
Snoek, Barbara C.
Heideman, Daniëlle A. M.
van Beurden, Marc
Steenbergen, Renske D. M.
Bleeker, Maaike C. G.
DNA methylation markers for cancer risk prediction of vulvar intraepithelial neoplasia
title DNA methylation markers for cancer risk prediction of vulvar intraepithelial neoplasia
title_full DNA methylation markers for cancer risk prediction of vulvar intraepithelial neoplasia
title_fullStr DNA methylation markers for cancer risk prediction of vulvar intraepithelial neoplasia
title_full_unstemmed DNA methylation markers for cancer risk prediction of vulvar intraepithelial neoplasia
title_short DNA methylation markers for cancer risk prediction of vulvar intraepithelial neoplasia
title_sort dna methylation markers for cancer risk prediction of vulvar intraepithelial neoplasia
topic Cancer Genetics and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048962/
https://www.ncbi.nlm.nih.gov/pubmed/33426639
http://dx.doi.org/10.1002/ijc.33459
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