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01.12.2017 | Research article | Ausgabe 1/2017 Open Access

BMC Cancer 1/2017

Morphological and phenotypical features of ovarian metastases in breast cancer patients

BMC Cancer > Ausgabe 1/2017
Inge T. A. Peters, Merle A. van der Steen, Bertine W. Huisman, Carina G. J .M. Hilders, Vincent T. H. B. M. Smit, Alexander L. Vahrmeijer, Cornelis F. M. Sier, J. Baptist Trimbos, Peter J. K. Kuppen
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Electronic supplementary material

The online version of this article (doi:10.​1186/​s12885-017-3191-y) contains supplementary material, which is available to authorized users.



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.


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).


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.


Examination of the actual ovarian transplants is recommended. A combination of targets is most appropriate to detect ovarian metastases by tumor-specific imaging.
Additional file 1: Figure S1. Immunohistochemical expression of tumor markers in invasive breast tumors and their corresponding ovarian metastases. Arrows indicate tumor cells that show heterogeneous expression of markers. Scale bars represent 100 μm. EMA, epithelial membrane antigen; Her2/neu, human epidermal growth receptor type 2; CEA, carcinoembryonic antigen; EpCAM, epithelial cell adhesion molecule. (TIFF 5316 kb)
Additional file 2: Table S2. List of participating hospitals. An overview is given of the treatment hospitals that approved the study design. (DOCX 14 kb)
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