Safety of ovarian tissue transplantation in patients with borderline ovarian tumors.

Abstract

Is transplantation of cryopreserved ovarian tissue from patients with borderline ovarian tumors (BOTs) a safe procedure? BOT cells were found in frozen-thawed and xenografted ovarian tissue in 1 of 11 BOT patients. The risk of reintroducing malignant cells upon ovarian tissue transplantation has been subject of debate for many years. Reimplantation of cryopreserved ovarian tissue from leukemia patients is unsafe, while results from studies of cryopreserved ovarian tissue from other forms of cancer, such as Hodgkin's lymphoma, are reassuring. Prospective experimental study conducted in an academic research unit using ovarian tissue from 11 patients undergoing cryopreservation for BOTs. Histology, immunohistochemistry (IHC) for mucin 1 (MUC1) and cytokeratin 7 (CK7) and molecular analysis by reverse transcription quantitative polymerase chain reaction (RT-qPCR) for CK7 and MUC1 were performed on frozen-thawed ovarian tissue from 11 patients. Long-term (5 months) xenografting of ovarian tissue in immunodeficient mice was performed. The xenografts were analyzed by histology, IHC and RT-qPCR, furthermore IHC for CD10, a marker of endometriosis, was performed on a selected sample. Analysis by histology, IHC and RT-qPCR indicated 10 of the ovarian tissue samples were negative. Analysis of the xenograft samples indicated nine were negative for malignant cells but in two xenografts glandular lesions were detected by histology. In these two xenografts, CK7 and MUC1 markers were demonstrated by IHC and CK7 expression also by RT-qPCR. A BOT was confirmed in the xenograft in which the original ovarian tissue was positive, while in the other case IHC demonstrated expression of endometriosis marker CD10. Cryopreserved ovarian fragments cannot be tested before transplantation, therefore the preimplantation analysis cannot guarantee that all cryopreserved fragments will be free of BOT cells. BOT cells can be found in cryopreserved ovarian tissue from BOT patients, therefore preimplantation analysis is an absolute prerequisite. Endometriosis can also be detected in cryopreserved ovarian tissue and caution should also be exercised in this scenario. This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (FNRS-PDR Convention T.0077.14, Télévie Grant 7.4590.16 awarded to Rossella Masciangelo, and Grant 5/4/150/5 awarded to Marie-Madeleine Dolmans), the Fonds Speciaux de Recherche, and the Foundation Against Cancer. None of the authors have any conflicting interests to declare.