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Serous borderline ovarian tumors in long-term culture: phenotypic and genotypic distinction from invasive ovarian carcinomas
  1. M. M.M. Woo*,
  2. C. M. Salamanca*,
  3. M. Miller,,
  4. J. Symowicz§,
  5. P. C.K. Leung*,
  6. C. Oliveira,
  7. T. G. Ehlen,
  8. C. B. Gilks,,
  9. D. Huntsman, and
  10. N. Auersperg*
  1. * Department of Obstetrics and Gynecology, University of British Columbia;
  2. Vancouver Cancer Centre, Vancouver, British Columbia;
  3. Department of Pathology, Genetic Pathology Evaluation Center, VHHSC and BC Cancer Agency, Vancouver, British Columbia;
  4. § Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and
  5. Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal
  1. Address correspondence and reprint requests to: Nelly Auersperg, MD, PhD, Department of Obstetrics and Gynecology, University of British Columbia, 2H30-4490 Oak Street, BC Women's Hospital, Vancouver, BC, Canada V6H 3V5. Email: auersper{at}


Serous borderline ovarian tumors (SBOTs) are differentiated, slow growing, noninvasive, and have a better prognosis than their invasive counterparts, but recurrence and progression to invasive carcinomas are common, and unlike high-grade serous carcinomas, they tend to be nonresponsive to chemotherapy. However, due to a lack of culture systems and animal models, information about the properties of SBOT and their changes with neoplastic progression is extremely limited. Our objective was to establish a cell culture model for SBOTs and to characterize their phenotype and genotype. We compared cultures derived from two SBOTs, one of which was a short-term culture containing a BRAF mutation but few other cytogenetic changes while the other culture developed into a spontaneously immortalized permanent cell line and had numerical and structural chromosomal abnormalities but lacked RAS/BRAF mutations. Both cultures formed whorl-like epithelial colonies and resembled low-grade invasive carcinomas by their secretion of CA125 and oviduct-specific glycoprotein, production of matrix metalloproteinases, E-cadherin expression, and telomerase activity. Other characteristics associated with neoplastic transformation, including invasiveness, anchorage-independent growth, and tumorigenicity, were not observed. Importantly, cell motility was reduced in both lines, likely contributing to the lack of invasiveness. The results reveal a striking phenotypic similarity between the two cell lines, regardless of their cytogenetic diversity, which suggests that their characteristic phenotype is regulated to a large degree by epigenetic and environmental factors. In conclusion, we have established the first permanent SBOT cell line, which provides a new model to elucidate the undefined relationship of SBOTs to invasive ovarian carcinomas.

  • genetics
  • invasion
  • low-malignant potential (LMP) ovarian tumor
  • ovarian cancer
  • serous borderline ovarian tumor (SBOT)

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