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Irregularly shaped inclusion cysts display increased expression of Ki67, Fas, Fas ligand, and procaspase-3 but relatively little active caspase-3
  1. K. A. Slot*,
  2. M. De Boer-Brouwer*,
  3. M. Voorendt*,
  4. D. M.D.S. Sie-Go,
  5. M. Ghahremani,
  6. J. H. Dorrington and
  7. K. J. Teerds*,§
  1. *Department of Biochemistry& Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
  2. Department of Pathology, University Medical Center, Utrecht University, Utrecht, The Netherlands
  3. Banting & Best Department of Medical Research, University of Toronto, Toronto, Canada
  4. §Human and Animal Physiology Group, Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands
  1. Address correspondence and reprint requests to: Katja J. Teerds, PhD, Human and Animal Physiology Group, Department of Animal Sciences, Wageningen University, Haarweg 10, 6709 PJ Wageningen, The Netherlands. Email: katja.teerds{at}wur.nl

Abstract

Human ovarian cancers are thought to arise from sequestered ovarian surface epithelial (OSE) cells that line the wall of inclusion cysts. Nevertheless, the early events toward neoplasia are not well understood. In this study, immunoreactivity for apoptotic proteins in human OSE of control and tumor ovarian sections was examined. Ki67, a marker for cell proliferation, was generally absent in the flat-to-cuboidal OSE cells on the ovarian surface and in regularly shaped inclusion cysts. Fas, Fas ligand, and caspase-3, components of the apoptotic pathway, were also largely absent. Ki67, Fas, Fas ligand, and procaspase-3 expression, though not active caspase-3 expression, was more frequently observed in epithelial cells lining irregularly shaped inclusion cysts, particularly in the columnar and Müllerian-like OSE cell types that resembled ovarian tumor OSE cells. Immunoreactivity for these factors as well as active caspase-3 was found frequently in ovarian tumors. We postulate that the appearance of the Fas system and its related proteins in sequestered columnar OSE cells of irregularly shaped inclusion cysts may contribute to balance cell growth with cell death, although little active caspase-3 expression was observed. Further studies are required to identify whether inhibition of apoptosis in inclusion cysts is an early event in ovarian carcinogenesis.

  • apoptosis
  • Fas system
  • inclusion cysts
  • ovarian cancer
  • proliferation

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