Indeed, the presence and number of CTCs are a poor prognostic factor in terms of relapse, survival, and the presence of micrometastases in several solid neoplasias including breast cancer [31]. patients cannot benefit from classic fertility preservation technologies for medical and/or personal reasons. Cryopreservation of ovarian tissue by slow-freezing followed by autotransplantation of thawed tissue provides an alternative method for fertility preservation in young women and even prepubertal girls [2]. While the exact number of ovarian tissue autotransplantations performed worldwide is unknown, this procedure has resulted in 13 reported births of healthy children [3], including two in our centre [4,5]. Despite these encouraging results, human ovarian cortex autografts still present some major limitations. A major concern is the possibility of reintroducing malignant cells into the patient. Indeed, as the ovarian biopsy and cryopreservation procedures are ideally performed prior to the administration of chemo- or radiotherapy, there is a risk of ovarian involvement and subsequent retransmission of the disease after autotransplantation. In a Japanese retrospective study performed on autopsy specimens, 22,4% of cancer patients under the age of 40 had ovarian metastases [6]. Most of Jaceosidin the metastases affecting ovaries are Jaceosidin derived from the gastrointestinal tract, breast cancer, or endometrial cancer [79]. It can be argued that these individuals are in advanced stages of the disease compared to women benefiting from ovarian tissue cryopreservation, but this underlines the fact that metastases can be found inside the ovarian tissue of young women. In fact, little is known about the presence of Rabbit polyclonal to AGTRAP malignant cells inside the graft and the risk of neoplasia retransmission after autotransplantation of cryopreserved ovarian tissue. Of the 13 live births reported in the literature, the autotransplanted Jaceosidin frozen-thawed ovarian tissue was derived from 8 cancer patients and two patients treated for benign disease [3]. Among these cancer patients, 4 had Hodgkin’s lymphoma (HL), one had breast cancer, one had Jaceosidin non-Hodgkin’s lymphoma (NHL), one had Ewing sarcoma, and one had neuroectodermic tumour. To date, there are no reports of disease recurrence following the procedure. However, using a mouse lymphoma model, it has been established that lymphoma can be transmitted through the graft even after cryopreservation and thawing of the ovarian tissue if cancer cells are present in the ovary [10]. Lymphoma can be contracted even with one small piece of ovarian tissue (~1 mm3) containing cancer cells [10]. The same results have been observed for leukaemia in a rat testis model [11]. In this study, fresh or frozen-thawed testicular cells from leukemic rats were injected in the testis of recipient rats. All of the recipient animals developed signs of leukaemia although a 36 day delay was observed in the appearance of symptoms in the frozen-thawed cell transplantation group [11]. Interestingly, it was also demonstrated that only 20 leukemic cells were sufficient to cause leukaemia after 3 weeks in 60% of the animals [11]. These two studies illustrate that malignant cells from haematological cancer can induce relapse in cured patients if these cells are present in the ovarian tissue. Additionally, these results provide evidence that cancer cells are resistant to freezing-thawing process. The safety of ovarian tissue transplantation in cancer patients should thus be addressed systematically for malignancies with low-to-moderate risk of ovarian implication. Herein, we will discuss the main tools that are currently available for the detection of disseminated cancer cells, specifically classic histology and immunohistochemistry and PCR and xenograft experiments. == 2. Analysis of Ovarian Tissue by Histology and Immunohistochemistry == In our centre, more than 30% of indications for ovarian tissue cryopreservation concern young patients affected by breast neoplasia. Others have also reported breast cancer as the main indication for fertility preservation [12,13]. In these cases, the risk of ovarian metastases is considered low to moderate (0.2% to 11%) [14]. Unfortunately, there is no established method for the detection of cancer cells in ovarian tissue. Only a few recent studies have analysed the incidence of ovarian metastasis in breast cancer patients who underwent cryopreservation procedure [1517]. The authors investigated the presence of breast cancer.