Abstract
BackgroundAutotransplantation 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.MethodsUsing 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).ResultsThe 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.ConclusionsExamination of the actual ovarian transplants is recommended. A combination of targets is most appropriate to detect ovarian metastases by tumor-specific imaging.
Highlights
Autotransplantation of frozen-thawed ovarian tissue is a method to preserve ovarian function and fertility in patients undergoing gonadotoxic therapy
This source population consisted of all patients who were diagnosed with primary invasive breast cancer at age < 41 years in the period 2000–2010 and who subsequently underwent an oophorectomy for any reason
Patient selection and clinicopathological characteristics According to the the Dutch Pathology Registry (PALGA) registry, 2648 patients were diagnosed with primary invasive breast cancer at age < 41 years in the period 2000–2010 in the Netherlands who subsequently underwent an oophorectomy (Fig. 1)
Summary
Autotransplantation of frozen-thawed ovarian tissue is a method to preserve ovarian function and fertility in patients undergoing gonadotoxic therapy. 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. Cortical ovarian tissue may contain malignant cells that could lead to reseeding of cancer upon autotransplantation. This risk of reintroducing malignant cells cannot be eliminated, since the current tumor detection methods (e.g. PCR, immunohistochemistry) jeopardize the ovarian tissue’s viability [4]. These methods can only be used to examine cortical ovarian strips that are not transplanted
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