[en] The cervical squamocolumnar (SC) junction is the site of a recently discovered "embryonic" cell population that was proposed as the cell of origin for cervical cancer and its precursors. How this population participates in cervical remodeling and neoplasia is unclear. In the present study, we analyzed the SC junction immunophenotype during pre and postnatal human and mouse development and in the adult, processes of metaplastic evolution of SC junction, microglandular change and early cervical neoplasia. Early in life, embryonic cervical epithelial cells were seen throughout the cervix and subsequently diminished in number to become concentrated at the SC junction in the adult. In all settings, there was a repetitive scenario in which cuboidal embryonic/SC junction cells gave rise to subjacent metaplastic basal/reserve cells with a switch from the SC junction positive to negative immunophenotype. This downward or basal (rather than upward or apical) evolution from progenitor cell to metaplastic progeny was termed reverse or "top down" differentiation. A similar pattern was noted in high grade squamous intraepithelial lesions (HSIL), suggesting HPV infection of the cuboidal SC junction cells initiated outgrowth of basally-oriented neoplastic progeny. The progressive loss of the embryonic/SC junction markers occurred with top-down differentiation during development, remodeling and early neoplasia. Interestingly, most low grade SILs were SC junction negative, implying infection of metaplastic progeny rather than the original SC junction cells. This proposed model of "top down" differentiation resolves the mystery of how SC junction cells both remodel the cervix and participate in neoplasia and provides for a second population of metaplastic progeny (including basal and reserve cells), the infection of which is paradoxically less likely to produce a biologically aggressive precursor. It also provides new targets in animal models to determine why the SC junction is uniquely susceptible to carcinogenic HPV infection. Copyright (c) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Disciplines :
Oncology
Author, co-author :
Herfs, Michael ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Vargas, Sara O.
Yamamoto, Yusuke
Howitt, Brooke E.
Nucci, Marisa R.
Hornick, Jason L.
McKeon, Frank D.
Xian, Wa
Crum, Christopher P.
Language :
English
Title :
A novel blueprint for "top down" differentiation defines the cervical squamocolumnar junction during development, reproductive life and neoplasia.
Publication date :
2013
Journal title :
Journal of Pathology
ISSN :
0022-3417
eISSN :
1096-9896
Publisher :
John Wiley & Sons, Chichester, United Kingdom
Volume :
229
Issue :
3
Pages :
460-8
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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