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]

Overview

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.[1]
  • Celomic epithelium itself is derived from mesothelium and forms lining of intraembryonic celom.[1]
  • 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.[1]
  • 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.[1][2]
  • Ovarian surface epithelium has also been postulated to give rise or form a part of ovarian granulosa cells during embryonic development.[1][2]

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.[1][3]
  • Catherins expressed by surface epithelium of ovaries may indicate potential for neoplastic transformation as summarized:[1][3][4][5][6]
    • 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.[1][4][7]
  • 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.[1][4]
  • 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.[1]
  • Ovarian surface epithelium undergo epithelio-mesenchymal transformation to replace ovarian stroma in ovulatory repair.[1]
  • 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.[1]

Role of hormones and growth factors on surface epithelium

Gonadotropin-releasing hormone

and gonadotropins[8]

  • Cell proliferation
Epidermal growth factor (EGF)[3][9]
  • 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)
  • Cell proliferation
  • Increased survival
Platelet-derived growth factor (PDGF)
  • Cell proliferation
Tissue necrosis factor-α (TNF-α)
  • Cell proliferation
  • Increased TNFα expression
Transfroming growth factor β (TGF-β)[10]
  • Decreased growth
Hepatocyte growth factor (HGF)
  • Decreased cellular adhesion
  • Increased survival and growth
Cytokines
  • Regulation of immune response
  • May increase vasculogenesis and survival

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 Auersperg N, Wong AS, Choi KC, Kang SK, Leung PC (April 2001). "Ovarian surface epithelium: biology, endocrinology, and pathology". Endocr. Rev. 22 (2): 255–88. doi:10.1210/edrv.22.2.0422. PMID 11294827.
  2. 2.0 2.1 Yoshinaga K, Hess DL, Hendrickx AG, Zamboni L (January 1988). "The development of the sexually indifferent gonad in the prosimian, Galago crassicaudatus crassicaudatus". Am. J. Anat. 181 (1): 89–105. doi:10.1002/aja.1001810110. PMID 3348150.
  3. 3.0 3.1 3.2 Siemens CH, Auersperg N (March 1988). "Serial propagation of human ovarian surface epithelium in tissue culture". J. Cell. Physiol. 134 (3): 347–56. doi:10.1002/jcp.1041340305. PMID 2450877.
  4. 4.0 4.1 4.2 Kruk PA, Uitto VJ, Firth JD, Dedhar S, Auersperg N (November 1994). "Reciprocal interactions between human ovarian surface epithelial cells and adjacent extracellular matrix". Exp. Cell Res. 215 (1): 97–108. doi:10.1006/excr.1994.1320. PMID 7525326.
  5. Davies BR, Worsley SD, Ponder BA (January 1998). "Expression of E-cadherin, alpha-catenin and beta-catenin in normal ovarian surface epithelium and epithelial ovarian cancers". Histopathology. 32 (1): 69–80. PMID 9522220.
  6. Sundfeldt K, Piontkewitz Y, Ivarsson K, Nilsson O, Hellberg P, Brännström M, Janson PO, Enerback S, Hedin L (June 1997). "E-cadherin expression in human epithelial ovarian cancer and normal ovary". Int. J. Cancer. 74 (3): 275–80. PMID 9221804.
  7. Osterholzer HO, Streibel EJ, Nicosia SV (August 1985). "Growth effects of protein hormones on cultured rabbit ovarian surface epithelial cells". Biol. Reprod. 33 (1): 247–58. PMID 3933584.
  8. Davies BR, Finnigan DS, Smith SK, Ponder BA (April 1999). "Administration of gonadotropins stimulates proliferation of normal mouse ovarian surface epithelium". Gynecol. Endocrinol. 13 (2): 75–81. PMID 10399050.
  9. Rodriguez GC, Berchuck A, Whitaker RS, Schlossman D, Clarke-Pearson DL, Bast RC (March 1991). "Epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer. II. Relationship between receptor expression and response to epidermal growth factor". Am. J. Obstet. Gynecol. 164 (3): 745–50. PMID 2003535.
  10. Berchuck A, Rodriguez G, Olt G, Whitaker R, Boente MP, Arrick BA, Clarke-Pearson DL, Bast RC (February 1992). "Regulation of growth of normal ovarian epithelial cells and ovarian cancer cell lines by transforming growth factor-beta". Am. J. Obstet. Gynecol. 166 (2): 676–84. PMID 1536252.