Epithelial ovarian tumors pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2]

Surface epithelium of ovaries

Surface epithelium of ovaries (OSE), once mistakenly referred as germinal epithelium, consists of single layer of flat to cuboidal epithelial cells. It is characterized by keratin types found in simple epithelium and functions in exchange between peritoneal cavity and the ovaries in addition to ovarian cycle.

Embryogenesis

• During embryonic development, surface epithelium of ovaries is a part of celomic epithelium.
• Celomic epithelium itself is derived from mesothelium and forms lining of intraembryonic celom.
• The future surface epithelium of ovaries then forms part of gonadal blastema and then undergoes a transformation cycle, multilayered papillary epithelium develops from simple flat to cuboidal epithelium but reverts back to simple flat to cuboidal epithelium by term.
• It is important to note that ovarian surface epithelium is the part of celomic epithelium that overlies the presumptive gonads and the celomic epithelium in proximity of gonads also gives rise to Mullerian (paramesonephric) ducts, that in future will develop into epthelium of most of the female reproductive tract including oviducts, endometrium and a part of cervix.
• Ovarian surface epithelium has also been postulated to give rise or form a part of ovarian granulosa cells during embryonic development.

Structural characteristics of ovarian surface epithelium in human adults

Cell type	Surface expression	Intercellular connection	Basement membrane
Single layer squamous-to-cuboidal epithelium	Keratin Mucin antigen MUC1 17β-hydroxysteroid dehydrogenase Cilia	Simple desmosomes Incomplete tight junctions Integrins Cadherins	Loosely attached Tunica albuginea that is less conspicuous of its testicular counterpart

• Keratin types that are expressed by ovarian surface epithelium are characteristic of simple epithelia such as keratin type 7, 8, 18 and 19.
• Catherins expressed by surface epithelium of ovaries may indicate potential for neoplastic transformation as summarized:
  • Surface epithelium of ovaries typically express N-cadherin.
  • E-cadherin is typically expressed in regions where cells are columnar.
  • This selective expression of E-cadherin in regions of metaplastic epithelium may indicate propensity for neoplastic transformation.
  • P-catherin, normally absent in adult surface epithelium of ovaries, is expressed in adenocarcinoma of ovaries.

Functions

• Two most important functions of human surface epithelium of ovaries are its role in transport and exchange between peritoneal cavity and ovaries, and its function in repair and rupture during ovulation.
• At present, its role in ovulatory rupture is not well-understood and is controversial. It is hypothesized that it contributes to follicular rupture through production of proteolytic enzymes.
• Epithelial need and ability of proliferation for repair of rupture and ovulatory defects is well-established and is thought to contribute the most in carcinogenesis of ovarian epithelium tumors.
• Ovarian surface epithelium undergo epithelio-mesenchymal transformation to replace ovarian stroma in ovulatory repair.
• The differentiation of surface epithelium of ovaries is, however, different from other epithelia because of its ability of differentiate into ectopic epithelium such as that of epithelium formed by Mullerian ducts.

Role of hormones and growth factors on surface epithelium

Gonadotropin-releasing hormone and gonadotropins	Cell proliferation
Epidermal growth factor (EGF)	Cell proliferation and differentiation Increased survival
Steroids	Decreased expression of GnRH receptors (estrogen) Regulation of hepatocyte growth factor and epidermal growth factor 9estrogen) Decreased expression of Transfroming growth factor β receptors (5α-dihydrotestosterone) May have direct effect on proliferation stimulation
Fibroblast growth factor (FGF)
Platelet-derived growth factor (PDGF)
Tissue necrosis factor-α (TNF-α)
Transfroming growth factor β (TGF-β)
Hepatocyte growth factor (HGF)
Cytokines