Identification of cell-surface markers for detecting breast cancer cells in ovarian tissue

Arch Gynecol Obstet. 2016 Aug;294(2):385-93. doi: 10.1007/s00404-016-4036-7. Epub 2016 Mar 5.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Autotransplantation; Breast cancer; Fertility preservation; Ovarian tissue; Tumor markers.

MeSH terms

  • Adult
  • Antigens, CD
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cadherins / metabolism
  • Cryopreservation*
  • Female
  • Fertility Preservation*
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Ovarian Neoplasms / pathology
  • Ovary / pathology
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Urokinase Plasminogen Activator / metabolism*

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • CDH1 protein, human
  • Cadherins
  • Receptors, Urokinase Plasminogen Activator
  • ERBB2 protein, human
  • Receptor, ErbB-2