Investigation of malignant cells in ovarian tissue from a patient with central nervous system primitive neuroectodermal tumor relapse after ovarian tissue transplantation

Author(s):  
Thu Yen Thi Nguyen ◽  
Alessandra Camboni ◽  
Rossella Masciangelo ◽  
Jacques Donnez ◽  
Marie‐Madeleine Dolmans
2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
T Y T Nguyen ◽  
L Cacciottola ◽  
A Camboni ◽  
M De Vos ◽  
I Demeestere ◽  
...  

Abstract Study question Is cryopreserved ovarian tissue transplantation safe in patients with central nervous system (CNS) tumors? Summary answer Cancer cell contamination was not detected in any ovarian samples from patients with CNS tumors by histological analysis, immunohistochemistry, molecular biology or long-term xenotransplantation. What is known already Frequently encountered CNS cancers in childhood include astrocytoma, medulloblastoma, ependymoma, glioblastoma and germinoma. CNS tumors have the capacity for extraneural metastases in 0.5-18% of cases. There are two publications reporting metastases to patients’ ovaries from medulloblastoma. Study design, size, duration Prospective experimental study conducted in an academic gynecology research laboratory using frozen-thawed ovarian tissue from 20 patients suffering from 6 types of CNS tumors, including the most common forms mentioned above and primitive neuroectodermal tumors (PNET). Five-month xenotransplantation was performed to severe combined immunodeficient (SCID) mice. Participants/materials, setting, methods Cryopreserved ovarian tissue from 20 patients with CNS cancers was thawed and analyzed for minimal disseminated disease and long-term xenografting to immunodeficient mice. The presence of malignant cells was assessed in both cryopreserved and xenografted ovarian tissue using histological analysis, immunohistochemistry for disease-­specific markers (neuron-specific enolase [NSE] and glial fibrillary acidic protein [GFAP]) and reverse transcription droplet digital polymerase chain reaction (RT-ddPCR) for quantification of GFAP gene amplification. Main results and the role of chance No malignant cells were detected in frozen-thawed ovarian tissue from any of the patients by histology, immunolabeling for NSE and GFAP, RT-ddPCR for detection of GFAP gene amplification or xenotransplantation to SCID mice. One patient successfully underwent frozen-thawed ovarian tissue transplantation, resulting in the birth of 3 healthy children, but suffered a recurrence of her PNET 6 years after reimplantation and sadly died. Scrupulous analysis of her remaining frozen tissue showed no infiltration by malignant cells, neither after thawing nor long-term xenotransplantation. No relationship was ever established between the patient’s relapsed cancer and reintroduction of her cryopreserved ovarian tissue. The risk of reseeding cancer cells when transplanting ovarian tissue in patients with CNS cancers can therefore be considered low. Limitations, reasons for caution The risk of ovarian metastases cannot be completely ruled out for any type of tumor because we cannot analyze the actual fragments that will be reimplanted. Wider implications of the findings Our results indicate that the risk of disseminated disease in ovarian tissue from CNS patients is minimal. This is useful information for doctors when counseling women looking to undergo ovarian tissue transplantation. Trial registration number Not applicable


2011 ◽  
Vol 13 (8) ◽  
pp. 866-879 ◽  
Author(s):  
S. Miller ◽  
H. A. Rogers ◽  
P. Lyon ◽  
V. Rand ◽  
M. Adamowicz-Brice ◽  
...  

2021 ◽  
Author(s):  
Thu Yen Thi Nguyen ◽  
Luciana Cacciottola ◽  
Alessandra Camboni ◽  
Joachim Ravau ◽  
Michel De Vos ◽  
...  

Abstract STUDY QUESTION Is there a possibility of reseeding cancer cells potentially present in frozen ovarian tissue from patients with central nervous system (CNS) tumours? SUMMARY ANSWER Malignancy reseeding in cryopreserved ovarian tissue from 20 patients with CNS tumours was not detected by histology, immunohistochemistry (IHC), molecular biology or xenotransplantation. WHAT IS KNOWN ALREADY Ovarian metastasis potential has been documented in patients with leukaemia, borderline ovarian tumours, advanced breast cancer and Ewing sarcoma. However, data on the safety of transplanting frozen-thawed ovarian tissue from cancer patients with CNS tumours are still lacking. STUDY DESIGN, SIZE, DURATION This prospective experimental study was conducted in an academic gynaecology research laboratory using cryopreserved ovarian cortex from 20 patients suffering from CNS tumours. Long-term (5 months) xenografting was performed in immunodeficient mice. PARTICIPANTS/MATERIALS, SETTING, METHODS Subjects enrolled in the study were suffering from one of six types of CNS tumours including medulloblastoma, ependymoma, primitive neuroectodermal tumours, astrocytoma, glioblastoma and germinoma. The presence of malignant cells was investigated with disease-specific markers for each patient in cryopreserved and xenografted ovarian tissue by histology, IHC via expression of neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and reverse transcription droplet digital polymerase chain reaction (RT-ddPCR) for quantification of GFAP and ENO2 gene amplification. MAIN RESULTS AND THE ROLE OF CHANCE Serial sections of cryopreserved and xenografted ovarian tissue from 20 patients showed no malignant cells by histology. All samples were negative for NSE and GFAP, although these neural markers were expressed extensively in the patients’ primary tumours. Analysis by RT-ddPCR revealed no cancer cells detected in cryopreserved and xenografted ovarian fragments from subjects with astrocytoma, ependymoma, glioblastoma or medulloblastoma. Taken together, the study found no evidence of malignancy seeding in frozen-thawed and xenotransplanted ovarian tissue from patients affected by CNS cancers. LIMITATIONS, REASONS FOR CAUTION This analysis cannot guarantee complete elimination of disseminated disease from all cryopreserved ovarian cortex, since we are unable to examine the fragments used for transplantation. WIDER IMPLICATIONS OF THE FINDINGS This is the first study to be conducted in patients with CNS cancers undergoing ovarian tissue cryopreservation and transplantation, and clearly demonstrates no tumour seeding in their frozen-thawed and xenografted tissue. This information is vital for doctors to provide patients with meaningful and accurate advice on the possibilities and risks of ovarian tissue reimplantation. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique–the Excellence of Science (FNRS–EOS), number 30443682 awarded to M.-M.D. and T.Y.T.N., FNRS grant number 5/4/150/5 and FNRS-PDR Convention grant number T.0077.14 awarded to M.-M.D., grant 2018-042 from the Foundation Against Cancer awarded to A.C., and private donations (Ferrero, de Spoelberch). The authors declare no competing financial interests. TRIAL REGISTRATION NUMBER N/A.


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