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)12885_2017_3191_MOESM1_ESM.tif
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)12885_2017_3191_MOESM2_ESM.docx
Jensen AK, Macklon KT, Fedder J, Ernst E, Humaidan P, Andersen CY. 86 succesful births and 9 ongoing pregnancies worldwide in women transplanted with frozen-thawed ovarian tissue: focus on birth and perinatal outcome in 40 of these children. J Assist Reprod Genet. 2016; doi: 10.1007/s10815-016-0843-9. PubMed
The Practice Committee of the American Society for Reproductive Medicine. Ovarian tissue cryopreservation: a committee opinion. Fertil Steril. 2014;101(5):1237–43. CrossRef
Bastings L, Beerendonk CCM, Westphal JR, Braat DDM, Peek R. Cryopreservation and Autotransplantation of Ovarian Tissue in Cancer Patients: Is It Safe? J Adolesc Young Adult Oncol. 2013;2(1):31–4. CrossRef
Bittinger SE, Nazaretian SP, Gook DA, Parmar C, Harrup RA, Stern CJ. Detection of Hodgkin lymphoma within ovarian tissue. Fertil Steril. 2011;95(2):803.e803–6. CrossRef
Peters IT, Stegehuis PL, Peek R, et al. Non-invasive detection of metastases and follicle density in ovarian tissue using full-field optical coherence tomography. Clin Cancer Res. 2016; doi: 10.1158/1078-0432.
Hammond RH, Bates TD, Clarke DG, et al. The immunoperoxidase localization of tumour markers in ovarian cancer: the value of CEA, EMA, cytokeratin and DD9. BJOG. 1991;98:73–83. CrossRef
Ang WX, Li Z, Chi Z, et al. Intraperitoneal immunotherapy with T cells stably and transiently expressing anti-EpCAM CAR in xenograft models of peritoneal carcinomatosis. Oncotarget 2017;doi:10.18632/oncotarget.14592.
Federa FMWV. Code for proper secondary use of human tissue in the Netherlands. 2002; http://www.federa.org/codes-conduct.
- Morphological and phenotypical features of ovarian metastases in breast cancer patients
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
- BioMed Central
Neu im Fachgebiet Onkologie
Mail Icon II