title: Identification of cell-surface markers for detecting breast cancer cells in ovarian tissue.
abstract: The safety of ovarian tissue autotransplantation in oncology patients cannot be ensured, as current tumor-detection methods compromise the ovarian tissue viability. Although non-destructive methods (for instance near-infrared fluorescence imaging) can discriminate malignant from healthy tissues while leaving the examined tissues unaffected, they require specific cell-surface tumor markers. We determined which tumor markers are suitable targets for tumor-specific imaging to exclude the presence of breast cancer cells in ovarian tissue.
  
  
  
  Immunohistochemistry was performed on formalin-fixed, paraffin-embedded specimens of ten ovaries from premenopausal patients. Additionally, we screened a tissue microarray containing tumor tissue cores from 24 breast cancer patients being eligible for ovarian tissue cryopreservation. The following cell-surface tumor markers were tested: E-cadherin, EMA (epithelial membrane antigen), Her2/neu (human epidermal growth factor receptor type 2), αvβ6 integrin, EpCAM (epithelial cell adhesion molecule), CEA (carcinoembryonic antigen), FR-α (folate receptor-alpha), and uPAR (urokinase-type plasminogen activator receptor). For each tumor, the percentage of positive breast tumor cells was measured.
  
  
  
  None of the ten ovaries were positive for any of the markers tested. However, all markers (except CEA and uPAR) were present on epithelial cells of inclusion cysts. E-cadherin was present in the majority of breast tumors: ≥90 % of tumor cells were positive for E-cadherin in 17 out of 24 tumors, and 100 % of tumor cells were positive in 5 out of 24 tumors.
  
  
  
  Of the markers tested, E-cadherin is the most suitable marker for a tumor-specific probe in ovarian tissue. Methods are required to distinguish inclusion cysts from breast tumor cells.
authors.affiliation: Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Inge T A
authors.initials: IT
authors.lastname: Peters
authors.affiliation: Department of Gynecology, Reinier de Graaf Hospital, Delft, The Netherlands.
authors.forename: Carina G J M
authors.initials: CG
authors.lastname: Hilders
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Cornelis F M
authors.initials: CF
authors.lastname: Sier
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Vahrmeijer
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Vincent T H B M
authors.initials: VT
authors.lastname: Smit
authors.affiliation: Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Baptist Trimbos
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. p.j.k.kuppen@lumc.nl.
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
mesh_terms: D000328:Adult; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D015925:Cryopreservation; D005260:Female; D059247:Fertility Preservation; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000473:pathology; D010053:Ovary / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015820:Cadherins; D018719:Erb-b2 Receptor Tyrosine Kinases; D055293:Receptors, Urokinase Plasminogen Activator; C513384:CDH1 protein, human; C508053:ERBB2 protein, human
keywords: Autotransplantation; Breast cancer; Fertility preservation; Ovarian tissue; Tumor markers