Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Avenue Mounier 52, bte. B1.52.02, 1200 Brussels, Belgium.
Société de Recherche pour l'Infertilité, Avenue Grandchamp 143, 1150 Brussels, Belgium.
Hum Reprod. 2018 Feb 1;33(2):212-219. doi: 10.1093/humrep/dex352.
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.
STUDY DESIGN, SIZE, DURATION: Prospective experimental study conducted in an academic research unit using ovarian tissue from 11 patients undergoing cryopreservation for BOTs.
PARTICIPANTS/MATERIALS, SETTING, METHODS: 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.
LIMITATIONS, REASONS FOR CAUTION: 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.
STUDY FUNDING/COMPETING INTEREST(S): 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.
从交界性卵巢肿瘤(BOT)患者中移植冷冻保存的卵巢组织是否安全?
在 11 名 BOT 患者中的 1 名患者的冷冻-解冻和异种移植卵巢组织中发现了 BOT 细胞。
多年来,卵巢组织移植后重新引入恶性细胞的风险一直存在争议。白血病患者冷冻保存卵巢组织的再植入是不安全的,而来自其他形式癌症(如霍奇金淋巴瘤)的冷冻保存卵巢组织研究结果则令人放心。
研究设计、大小、持续时间:在一个学术研究单位进行的前瞻性实验研究,使用 11 名因 BOT 而进行冷冻保存的患者的卵巢组织。
参与者/材料、地点、方法:对 11 名患者的冷冻-解冻卵巢组织进行组织学、黏蛋白 1(MUC1)和细胞角蛋白 7(CK7)的免疫组织化学(IHC)以及 CK7 和 MUC1 的逆转录定量聚合酶链反应(RT-qPCR)分析。对卵巢组织进行了长达 5 个月的免疫缺陷小鼠异种移植。通过组织学、IHC 和 RT-qPCR 分析异种移植物,还对选定的样本进行了 CD10(子宫内膜异位症的标志物)的 IHC 分析。
组织学、IHC 和 RT-qPCR 分析表明 10 个卵巢组织样本为阴性。对异种移植物样本的分析表明,9 个样本中没有恶性细胞,但在两个异种移植物中通过组织学检测到腺体病变。在这两个异种移植物中,通过 IHC 检测到 CK7 和 MUC1 标志物,并且通过 RT-qPCR 检测到 CK7 表达。在原始卵巢组织呈阳性的异种移植物中证实存在 BOT,而在另一个病例中,IHC 显示子宫内膜异位症标志物 CD10 的表达。
局限性、谨慎的原因:冷冻保存的卵巢碎片在移植前无法进行测试,因此植入前分析不能保证所有冷冻保存的碎片都没有 BOT 细胞。
BOT 细胞可在 BOT 患者的冷冻保存卵巢组织中找到,因此植入前分析是绝对必要的。在冷冻保存的卵巢组织中也可以检测到子宫内膜异位症,因此在这种情况下也应谨慎。
研究资助/利益冲突:本研究得到了比利时国家科学研究基金会(FNRS-PDR 公约 T.0077.14、Télévie 赠款 7.4590.16 授予 Rossella Masciangelo,以及赠款 5/4/150/5 授予 Marie-Madeleine Dolmans)、特别研究基金和抗癌基金会的支持。作者均无利益冲突。