title: Putative stem cells and epithelial-mesenchymal transition revealed in sections of ovarian tumor in patients with serous ovarian carcinoma using immunohistochemistry for vimentin and pluripotency-related markers.
abstract: BACKGROUND
  The mechanism of aggressive character of ovarian cancer and unsuccessful treatment of women with this deadly disease has been recently explained by the theory of cancer stem cells (CSCs). It has been reported that ovarian carcinogenesis and progression of disease is associated with epithelial-mesenchymal transition (EMT). EMT, a physiological cell process during embryonic development and later in life during regeneration, could, when induced in pathological condition, generate CSCs-like cells. Until now EMT in the ovarian tissue has been mainly studied in cell cultures in vitro. The aim of this study was to focus on in situ morphological changes in the ovarian surface epithelium of tumor tissue in women with epithelial ovarian cancer after we applied the antibodies for markers of EMT vimentin and pluripotency-related markers NANOG, SOX2 and SSEA-4.
  
  
  METHODS
  We analyzed ovarian tissue sections of 20 women with high grade serous ovarian carcinoma. After eosin and hematoxylin staining, used in standard practice, immunohistochemistry was performed for vimentin and markers of pluripotency: NANOG, SSEA-4 and SOX2. We focused on the ovarian surface epithelium in order to observe morphological changes in tumor tissue.
  
  
  RESULTS
  Among epithelial cells of the ovarian surface epithelium in women with serous ovarian carcinoma we observed a population of small NANOG-positive cells with diameters of up to 5 μm and nuclei, which filled almost the entire cell volumes. These small NANOG-positive cells were in some cases concentrated in the regions with morphologically changed epithelial cells. In these regions, a population of bigger round cells with diameters of 10-15 μm with large nuclei, and positively stained for vimentin, NANOG and other markers of pluripotnecy, were released from the surface epithelium. These cells are proposed as CSCs, and possibly originate from small stem cells among epithelial cells. They formed typical cell clusters, invaded the tissue by changing their round shape into a mesenchymal-like phenotype, and contributed to the manifestation of ovarian cancer.
  
  
  CONCLUSIONS
  Our findings show morphological changes in the ovarian surface epithelium in tumor slides of high grade serous ovarian carcinoma and provide a new population of putative CSCs.
authors.affiliation: Department of Obstetrics and Gynaecology, University Medical Centre Ljubljana, Slajmerjeva 3, 1000, Ljubljana, Slovenia.
authors.forename: Natasa
authors.initials: N
authors.lastname: Kenda Suster
authors.affiliation: Department of Obstetrics and Gynaecology, University Medical Centre Ljubljana, Slajmerjeva 3, 1000, Ljubljana, Slovenia.
authors.forename: Spela
authors.initials: S
authors.lastname: Smrkolj
authors.affiliation: Department of Obstetrics and Gynaecology, University Medical Centre Ljubljana, Slajmerjeva 3, 1000, Ljubljana, Slovenia. irma.virant@gmail.com.
authors.forename: Irma
authors.initials: I
authors.lastname: Virant-Klun
mesh_terms: D015415:Biomarkers; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000473:pathology; D049109:Cell Proliferation; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000071317:Nanog Homeobox Protein / Q000378:metabolism; D060787:Neoplasm Grading; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D055746:Stage-Specific Embryonic Antigens / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D000071317:Nanog Homeobox Protein; D055748:SOXB1 Transcription Factors; D055746:Stage-Specific Embryonic Antigens; D014746:Vimentin; C066584:stage-specific embryonic antigen-4
keywords: Cancer stem cells; Epithelial-mesenchymal transition; Immunohistochemistry; Markers of pluripotency; Ovarian cancer