Observations on the origin of ovarian cortical inclusion cysts in women undergoing risk‐reducing salpingo‐oophorectomy

Abstract

These results, and the increased ratio of PAX8 to calretinin CICs from premenopausal to postmenopausal, show that many PAX8 CICs probably arise from metaplasia of OSE-derived CICs. The proportion of PAX /calretinin CICs arising from OSE-derived CICs is unclear, but our results strongly support the proposal that many Müllerian-CICs arise from OSE via metaplasia.

A Study of High-Grade Serous Ovarian Cancer Origins Implicates the SOX18 Transcription Factor in Tumor Development

“…Historically, OSECs were thought to be the precursor cell type for HGSOC, and there remains significant, and often overlooked, evidence supporting this hypothesis. First, OSECs can express many prominent HGSOC markers, including PAX8 (Adler et al, 2015;Park et al, 2018). Second, OSECs from women at high risk of ovarian cancer are more committed to an epithelial phenotype and in culture maintain expression of CA125 longer than OSECs from non-high-risk women (Dyck et al, 1996).…”

“…Third, occult cancers have been detected in the ovaries of women undergoing prophylactic risk reducing oophorectomy and can occur without evidence of lesions in the fallopian tube (Powell et al, 2005). Fourth, a recent detailed analysis of almost 60 ovaries documented evidence for metaplasia of ovarian epithelium to a M€ ullerian phenotype, suggesting that adoption of a more fallopian-like morphology may be an early step in the neoplastic transformation of OSECs (Park et al, 2018).…”

“…Historically, HGSOCs were thought to arise from OSECs, an atypical epithelial cell type with mesothelial features and inherent phenotypic plasticity and heterogeneity (Kruk and Auersperg, 1992;Park et al, 2018). However, examples of early-stage ovarian carcinoma arising from OSECs in vivo are rare.…”

Integrated Molecular Profiling Studies to Characterize the Cellular Origins of High-Grade Serous Ovarian Cancer

“…Our understanding of the cellular origins of HGSOC and key transcription factor networks deregulated during HGSOC development has been restricted by the lack of substantial molecular profiling data for the suggested precursor tissues, ovarian surface epithelial cells (OSECs) and fallopian tube secretory epithelial cells (FTSECs). Historically, HGSOCs were thought to arise from OSECs, an atypical epithelial cell type with mesothelial features and inherent phenotypic plasticity and heterogeneity 1,2 .…”

Multi-Tissue Transcriptome-Wide Association Study Identifies 26 Novel Candidate Susceptibility Genes for High Grade Serous Epithelial Ovarian Cancer

“…While our transcriptome-wide significant findings were primarily driven by reference panel size, our polygenic findings support this: a greater proportion of GWAS heritability was explained by all expression in the ovarian tumor tissues rather than breast and prostate tumors. Moreover, the genetic correlation between FTSECs and HGSOCs was higher than between OSECs and HGSOCs; published data strongly suggest that FTSECs are the most common precursor cell type for HGSOC (19‐23), although some data suggest that OSECs may be a precursor cell type for specific molecular subgroups of HGSOC (37‐39). Furthermore, only 2/21 genes we identified were transcriptome-wide significant in ovary tissues from the GTEx Consortium (with 11/21 significant across all GTEx tissues); likely because whole ovaries are predominantly composed of stromal (rather than epithelial) cells and the sample size in GTEx is small (n=54).…”