BACKGROUND: Autotransplantation of frozen-thawed ovarian tissue is a method to 
preserve ovarian function and fertility in patients undergoing gonadotoxic 
therapy. In oncology patients, the safety cannot yet be guaranteed, since 
current tumor detection methods can only exclude the presence of malignant cells 
in ovarian fragments that are not transplanted. We determined the need for a 
novel detection method by studying the distribution of tumor cells in ovaries 
from patients with breast cancer. Furthermore, we examined which cell-surface 
proteins are suitable as a target for non-invasive tumor-specific imaging of 
ovarian metastases from invasive breast cancer.
METHODS: Using the nationwide database of the Dutch Pathology Registry (PALGA), 
we identified a cohort of 46 women with primary invasive breast cancer and 
ovarian metastases. The localization and morphology of ovarian metastases were 
determined on hematoxylin-and-eosin-stained sections. The following cell-surface 
markers were immunohistochemically analyzed: E-cadherin, epithelial membrane 
antigen (EMA), human epidermal growth receptor type 2 (Her2/neu), 
carcinoembryonic antigen (CEA), αvβ6 integrin and epithelial cell adhesion 
molecule (EpCAM).
RESULTS: The majority of ovarian metastases (71%) consisted of a solitary 
metastasis or multiple distinct nodules separated by uninvolved ovarian tissue, 
suggesting that ovarian metastases might be overlooked by the current detection 
approach. Combining the targets E-cadherin, EMA and Her2/neu resulted in nearly 
100% detection of ductal ovarian metastases, whereas the combination of EMA, 
Her2/neu and EpCAM was most suitable to detect lobular ovarian metastases.
CONCLUSIONS: Examination of the actual ovarian transplants is recommended. A 
combination of targets is most appropriate to detect ovarian metastases by 
tumor-specific imaging.