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Switches of SOX17 and SOX2 expression in the development of squamous metaplasia and squamous intraepithelial lesions of the uterine cervix

AIMS: The dynamics and topographical distribution of SOX17 and SOX2 expression was studied in the transformation zone (TZ) of the uterine cervix. This TZ is a dynamic area where switches from glandular into squamous epithelium can be recognized, new squamocolumnar junctions are formed, and premalign...

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Autores principales: Moshi, Jobran M., Hoogduin, Klaas J., Ummelen, Monique, Henfling, Mieke E. R., van Engeland, Manon, Wouters, Kim A. D., Stoop, Hans, Demers, Imke, Looijenga, Leendert H. J., Ramaekers, Frans C. S., Hopman, Anton N. H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476841/
https://www.ncbi.nlm.nih.gov/pubmed/32644288
http://dx.doi.org/10.1002/cam4.3201
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author Moshi, Jobran M.
Hoogduin, Klaas J.
Ummelen, Monique
Henfling, Mieke E. R.
van Engeland, Manon
Wouters, Kim A. D.
Stoop, Hans
Demers, Imke
Looijenga, Leendert H. J.
Ramaekers, Frans C. S.
Hopman, Anton N. H.
author_facet Moshi, Jobran M.
Hoogduin, Klaas J.
Ummelen, Monique
Henfling, Mieke E. R.
van Engeland, Manon
Wouters, Kim A. D.
Stoop, Hans
Demers, Imke
Looijenga, Leendert H. J.
Ramaekers, Frans C. S.
Hopman, Anton N. H.
author_sort Moshi, Jobran M.
collection PubMed
description AIMS: The dynamics and topographical distribution of SOX17 and SOX2 expression was studied in the transformation zone (TZ) of the uterine cervix. This TZ is a dynamic area where switches from glandular into squamous epithelium can be recognized, new squamocolumnar junctions are formed, and premalignant lesions originate. SOX17 and SOX2 show mutually exclusive expression patterns in the normal uterine cervix, with SOX2 being exclusively found in squamous epithelium, while SOX17 is detected in endocervical columnar cells and reserve cells. METHODS AND RESULTS: Normal cervices and squamous intraepithelial lesions (SIL) were studied with immunohistochemistry, methylation of SOX17, human papilloma virus (HPV) genotyping, and in situ hybridization. In the TZ squamous metaplasia originating from these reserve cells can still show SOX17 expression, while also remnants of SOX17‐positive immature metaplasia can be recognized in the normal squamous epithelium. SOX17 expression is gradually lost during maturation, resulting in the exclusive expression of SOX2 in the majority of (SIL). This loss of SOX17 expression is independent of methylation of the CpG island in its promotor region. HPV can be detected in SOX17‐positive immature metaplastic regions in the immediate vicinity of SOX2‐positive SIL, suggesting that switches in SOX17 and 2 expression can occur upon HPV infection. CONCLUSIONS: This switch in expression, and the strong association between the distribution of reserve cells and squamous areas within the columnar epithelium in the TZ, suggests that reserve cell proliferations, next to basal cells in the squamous epithelium, are potential targets for the formation of squamous lesions upon viral infection.
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spelling pubmed-74768412020-09-11 Switches of SOX17 and SOX2 expression in the development of squamous metaplasia and squamous intraepithelial lesions of the uterine cervix Moshi, Jobran M. Hoogduin, Klaas J. Ummelen, Monique Henfling, Mieke E. R. van Engeland, Manon Wouters, Kim A. D. Stoop, Hans Demers, Imke Looijenga, Leendert H. J. Ramaekers, Frans C. S. Hopman, Anton N. H. Cancer Med Cancer Biology AIMS: The dynamics and topographical distribution of SOX17 and SOX2 expression was studied in the transformation zone (TZ) of the uterine cervix. This TZ is a dynamic area where switches from glandular into squamous epithelium can be recognized, new squamocolumnar junctions are formed, and premalignant lesions originate. SOX17 and SOX2 show mutually exclusive expression patterns in the normal uterine cervix, with SOX2 being exclusively found in squamous epithelium, while SOX17 is detected in endocervical columnar cells and reserve cells. METHODS AND RESULTS: Normal cervices and squamous intraepithelial lesions (SIL) were studied with immunohistochemistry, methylation of SOX17, human papilloma virus (HPV) genotyping, and in situ hybridization. In the TZ squamous metaplasia originating from these reserve cells can still show SOX17 expression, while also remnants of SOX17‐positive immature metaplasia can be recognized in the normal squamous epithelium. SOX17 expression is gradually lost during maturation, resulting in the exclusive expression of SOX2 in the majority of (SIL). This loss of SOX17 expression is independent of methylation of the CpG island in its promotor region. HPV can be detected in SOX17‐positive immature metaplastic regions in the immediate vicinity of SOX2‐positive SIL, suggesting that switches in SOX17 and 2 expression can occur upon HPV infection. CONCLUSIONS: This switch in expression, and the strong association between the distribution of reserve cells and squamous areas within the columnar epithelium in the TZ, suggests that reserve cell proliferations, next to basal cells in the squamous epithelium, are potential targets for the formation of squamous lesions upon viral infection. John Wiley and Sons Inc. 2020-07-09 /pmc/articles/PMC7476841/ /pubmed/32644288 http://dx.doi.org/10.1002/cam4.3201 Text en © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://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 Biology
Moshi, Jobran M.
Hoogduin, Klaas J.
Ummelen, Monique
Henfling, Mieke E. R.
van Engeland, Manon
Wouters, Kim A. D.
Stoop, Hans
Demers, Imke
Looijenga, Leendert H. J.
Ramaekers, Frans C. S.
Hopman, Anton N. H.
Switches of SOX17 and SOX2 expression in the development of squamous metaplasia and squamous intraepithelial lesions of the uterine cervix
title Switches of SOX17 and SOX2 expression in the development of squamous metaplasia and squamous intraepithelial lesions of the uterine cervix
title_full Switches of SOX17 and SOX2 expression in the development of squamous metaplasia and squamous intraepithelial lesions of the uterine cervix
title_fullStr Switches of SOX17 and SOX2 expression in the development of squamous metaplasia and squamous intraepithelial lesions of the uterine cervix
title_full_unstemmed Switches of SOX17 and SOX2 expression in the development of squamous metaplasia and squamous intraepithelial lesions of the uterine cervix
title_short Switches of SOX17 and SOX2 expression in the development of squamous metaplasia and squamous intraepithelial lesions of the uterine cervix
title_sort switches of sox17 and sox2 expression in the development of squamous metaplasia and squamous intraepithelial lesions of the uterine cervix
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476841/
https://www.ncbi.nlm.nih.gov/pubmed/32644288
http://dx.doi.org/10.1002/cam4.3201
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