title: PAX8 expression in ovarian surface epithelial cells.
abstract: High-grade serous ovarian carcinoma (HGSOC) is usually diagnosed at a late stage and is associated with poor prognosis. Understanding early stage disease biology is essential in developing clinical biomarkers to detect HGSOC earlier. While recent studies indicate that HGSOCs arise from fallopian tube secretory epithelial cells, a considerable body of evidence suggests that HGSOC can also arise from ovarian surface epithelial cells (OSECs). PAX8 is overexpressed in HGSOCs and expressed in fallopian tube secretory epithelial cells, but there are conflicting reports about PAX8 expression in OSECs. The purposes of this study were to comprehensively characterize PAX8 expression in a large series of OSECs and to investigate the role of PAX8 in early HGSOC development. PAX8 protein expression was analyzed in the OSECs of 27 normal ovaries and 7 primary OSEC cultures using immunohistochemistry and immunofluorescent cytochemistry. PAX8 messenger RNA expression was quantified in 66 primary OSEC cultures. Cellular transformation was evaluated in OSECs expressing a PAX8 construct. PAX8 was expressed by 44% to 71% of OSECs. Calretinin and E-cadherin were frequently coexpressed with PAX8. Expression of PAX8 in OSECs decreased cellular migration (P = .028), but had no other effects on cellular transformation. In addition, PAX8 expression was significantly increased (P = .003) in an in vitro stepwise model of neoplastic transformation. In conclusion, PAX8 is frequently expressed by OSECs, and endogenous levels of PAX8 expression are non-transforming. These data indicate that in OSECs, PAX8 expression may represent a normal state and that OSECs may represent an origin of HGSOCs.
authors.affiliation: Department of Preventive Medicine, University of Southern California/Keck School of Medicine, Los Angeles, CA 90033. Electronic address: emilyadl@usc.edu.
authors.forename: Emily
authors.initials: E
authors.lastname: Adler
authors.affiliation: Departments of Medicine and Pathology, University of Southern California/Keck School of Medicine, Los Angeles, CA 90033. Electronic address: mhawechf@usc.edu.
authors.forename: Paulette
authors.initials: P
authors.lastname: Mhawech-Fauceglia
authors.affiliation: Department of Preventive Medicine, University of Southern California/Keck School of Medicine, Los Angeles, CA 90033. Electronic address: gayther@usc.edu.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Gayther
authors.affiliation: Department of Preventive Medicine, University of Southern California/Keck School of Medicine, Los Angeles, CA 90033. Electronic address: Kate.Lawrenson@med.usc.edu.
authors.forename: Kate
authors.initials: K
authors.lastname: Lawrenson
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D064032:Calbindin 2 / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000378:metabolism* / Q000473:pathology; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection
chemical_list: D015703:Antigens, CD; C576764:CALB2 protein, human; C513384:CDH1 protein, human; D015820:Cadherins; D064032:Calbindin 2; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger
keywords: CMYC; Fallopian tube epithelial cells; High-grade serous ovarian carcinoma; Inclusion cyst; Ovarian surface epithelium; PAX8