Article (Scientific journals)
The PAX2-null immunophenotype defines multiple lineages with common expression signatures in benign and neoplastic oviductal epithelium.
Ning, Gang; Bijron, Jonathan G.; Yamamoto, Yusuke et al.
2014In Journal of Pathology, 234, p. 478-487
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Keywords :
ALDH1; Fallopian tube; PAX2; serous carcinoma; stem cell
Abstract :
[en] The oviducts contain high-grade serous cancer (HGSC) precursors (serous tubal intraepithelial neoplasia or STINs), which are gamma-H2AXp - and TP53 mutation-positive. Although they express wild-type p53, secretory cell outgrowths (SCOUTs) are associated with older age and serous cancer; moreover, both STINs and SCOUTs share a loss of PAX2 expression (PAX2n ). We evaluated PAX2 expression in proliferating adult and embryonic oviductal cells, normal mucosa, SCOUTs, Walthard cell nests (WCNs), STINs, and HGSCs, and the expression of genes chosen empirically or from SCOUT expression arrays. Clones generated in vitro from embryonic gynaecological tract and adult Fallopian tube were Krt7p /PAX2n /EZH2p and underwent ciliated (PAX2n /EZH2n /FOXJ1p ) and basal (Krt7n /EZH2n /Krt5p ) differentiation. Similarly, non-ciliated cells in normal mucosa were PAX2p but became PAX2n in multi-layered epithelium undergoing ciliated or basal (WCN) cell differentiation. PAX2n SCOUTs fell into two groups: type 1 were secretory or secretory/ciliated with a 'tubal' phenotype and were ALDH1n and beta-cateninmem (membraneous only). Type 2 displayed a columnar to pseudostratified (endometrioid) phenotype, with an EZH2p , ALDH1p , beta-cateninnc (nuclear and cytoplasmic), stathminp , LEF1p , RCN1p , and RUNX2p expression signature. STINs and HGSCs shared the type 1 immunophenotype of PAX2n , ALDH1n , beta-cateninmem , but highly expressed EZH2p , LEF1p , RCN1p , and stathminp . This study, for the first time, links PAX2n with proliferating fetal and adult oviductal cells undergoing basal and ciliated differentiation and shows that this expression state is maintained in SCOUTs, STINs, and HGSCs. All three entities can demonstrate a consistent perturbation of genes involved in potential tumour suppressor gene silencing (EZH2), transcriptional regulation (LEF1), regulation of differentiation (RUNX2), calcium binding (RCN1), and oncogenesis (stathmin). This shared expression signature between benign and neoplastic entities links normal progenitor cell expansion to abnormal and neoplastic outgrowth in the oviduct and exposes a common pathway that could be a target for early prevention. Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Disciplines :
Oncology
Author, co-author :
Ning, Gang
Bijron, Jonathan G.
Yamamoto, Yusuke
Wang, Xia
Howitt, Brooke E.
Herfs, Michael ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Yang, Eric
Hong, Yue
Cornille, Maxence
Wu, Lingyan
Hanamornroongruang, Suchanan
McKeon, Frank D.
Crum, Christopher P.
Xian, Wa
More authors (4 more) Less
Language :
English
Title :
The PAX2-null immunophenotype defines multiple lineages with common expression signatures in benign and neoplastic oviductal epithelium.
Publication date :
2014
Journal title :
Journal of Pathology
ISSN :
0022-3417
eISSN :
1096-9896
Publisher :
John Wiley & Sons, Inc, Chichester, United Kingdom
Volume :
234
Pages :
478-487
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Available on ORBi :
since 15 October 2014

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