Morphological and phenotypical features of ovarian metastases in breast cancer patients.
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.
Department of Gynecology, Leiden University Medical Center, Leiden, the Netherlands.
Inge T A
IT
Peters
Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
Merle A
MA
van der Steen
Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
Bertine W
BW
Huisman
Department of Gynecology, Reinier de Graaf Hospital, Delft, the Netherlands.
Carina G J M
CG
Hilders
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
Vincent T H B M
VT
Smit
Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
Alexander L
AL
Vahrmeijer
Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
Cornelis F M
CF
Sier
Department of Gynecology, Leiden University Medical Center, Leiden, the Netherlands.
J Baptist
JB
Trimbos
Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands. p.j.k.kuppen@lumc.nl.
Peter J K
PJ
Kuppen
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D015331:Cohort Studies; D000071858:Epithelial Cell Adhesion Molecule / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000556:secondary; D010053:Ovary / Q000378:metabolism* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D015820:Cadherins; D002272:Carcinoembryonic Antigen; D000071858:Epithelial Cell Adhesion Molecule; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
breast cancer; fertility preservation; ovarian metastases; ovarian tissue autotransplantation; tumor markers; tumor-specific imaging