title: Irregularly shaped inclusion cysts display increased expression of Ki67, Fas, Fas ligand, and procaspase-3 but relatively little active caspase-3.
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.
authors.affiliation: Department of Biochemistry & Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: K A
authors.initials: KA
authors.lastname: Slot
authors.forename: M
authors.initials: M
authors.lastname: de Boer-Brouwer
authors.forename: M
authors.initials: M
authors.lastname: Voorendt
authors.forename: D M D S
authors.initials: DM
authors.lastname: Sie-Go
authors.forename: M
authors.initials: M
authors.lastname: Ghahremani
authors.forename: J H
authors.initials: JH
authors.lastname: Dorrington
authors.forename: K J
authors.initials: KJ
authors.lastname: Teerds
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D016022:Case-Control Studies; D053148:Caspase 3; D020169:Caspases / Q000235:genetics; D049109:Cell Proliferation; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000235:genetics; D008875:Middle Aged; D010048:Ovarian Cysts / Q000235:genetics / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000601:surgery; D010052:Ovariectomy; D010053:Ovary / Q000166:cytology* / Q000473:pathology; D011336:Probability; D011379:Prognosis; D012016:Reference Values; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques; D019014:fas Receptor / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019014:fas Receptor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases