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Reproduction & Fertility Apr 2021The Ubiquitous Transcribed Y ( a.k.a. ) AZFa candidate gene on the human Y chromosome and its paralog on the X chromosome, (a.k.a. ), encode a histone lysine...
UNLABELLED
The Ubiquitous Transcribed Y ( a.k.a. ) AZFa candidate gene on the human Y chromosome and its paralog on the X chromosome, (a.k.a. ), encode a histone lysine demethylase removing chromatin H3K27 methylation marks at genes transcriptional start sites for activation. Both proteins harbour the conserved Jumonji C (JmjC) domain, functional in chromatin metabolism, and an extended N-terminal tetratricopeptide repeat (TPR) block involved in specific protein interactions. Specific antisera for human UTY and UTX proteins were developed to distinguish the expression of both proteins in human germ cells by immunohistochemical experiments on appropriate tissue sections. In the male germ line, UTY was expressed in the fraction of A spermatogonia located at the basal membrane, probably including spermatogonia stem cells. UTX expression was more spread in all spermatogonia and in early spermatids. In female germ line, UTX expression was found in the primordial germ cells of the ovary. UTY was also expressed during fetal male germ cell development, whereas UTX expression was visible only at distinct gestation weeks. Based on these results and the conserved neighboured location of and in Yq11 found in mammals of distinct lineages, we conclude that such as is part of the Azoospermia factor a (AZFa) locus functioning in human spermatogonia to support the balance of their proliferation-differentiation rate before meiosis. Comparable UTY and DDX3Y expression was also found in gonadoblastoma and dysgerminoma cells found in germ cell nests of the dysgenetic gonads of individuals with disorders of sexual development and a Y chromosome in karyotype (DSD-XY). This confirms that AZFa overlaps with GBY the Gonadoblastoma susceptibility Y locus, and includes the gene.
LAY SUMMARY
AZFa Y genes are involved in human male germ cells development and support gonadoblastoma (germ cell tumour precursor cells) in the aberrant germ cells of the gonads of females with genetic disorders of sexual development. The AZFa gene on the male Y chromosome is equivalent to on the female X chromosome. These genes are involved in removing gene regulators to enable activation of other genes (i.e. removal of histone methylation known as epigenetic modifications). We wanted to learn the function of UTY and UTX in developing sperm and eggs in human tissues and developed specific antibodies to detect both proteins made by these genes. Both UTY and UTX proteins were detected in adult and fetal sperm precursor cells (spermatogonia). UTX was detected in egg precursor cells (primordial germ cells). UTY was detected in gonadoblastoma and dysgerminoma tumour cells (germ cell tumours originating from genetic disorders of sexual development due to having a Y chromosome). Based on our study, we conclude that UTY is not only part of AZFa, but also of GBY the overlapping gonadoblastoma susceptibility Y region.
Topics: Adult; Animals; Chromatin; Chromosomes, Human, Y; DEAD-box RNA Helicases; Dysgerminoma; Female; Gonadoblastoma; Histone Demethylases; Humans; Male; Mammals; Minor Histocompatibility Antigens; Neoplasms, Germ Cell and Embryonal; Nuclear Proteins; Ovarian Neoplasms; Semen; Spermatogonia
PubMed: 35128450
DOI: 10.1530/RAF-20-0049 -
Journal of Ovarian Research Sep 2019Gonadoblastoma (GB) is a rare mixed germ cell-sex cord-stromal tumour, first described in humans, commonly found in dysgenetic gonads of intersex patients that have a Y...
BACKGROUND
Gonadoblastoma (GB) is a rare mixed germ cell-sex cord-stromal tumour, first described in humans, commonly found in dysgenetic gonads of intersex patients that have a Y chromosome. However, this entity in not recognized in the WHO classification of tumours of genital system of domestic animals. Herein, we describe a case of ovarian gonadoblastoma with proliferation of dysgerminoma and sex cord-stromal tumour components, in a phenotypically and cytogenetically normal bitch.
CASE PRESENTATION
A 17-year-old cross-breed bitch had a firm, grey-white multinodular mass in the left ovary. The tumour was submitted to histopathological examination and Y chromosome detected through karyotype analysis and PCR studies. Microscopically, the ovary was almost replaced by an irregular neoplasm composed of three distinct, intermixed elements: dysgerminoma, mixed germ cell-sex cord-stromal tumour resembling human GB and a proliferative sex cord-stromal tumour component. The germ cells of gonadoblastoma and dysgerminoma components were immunoreactive for c-KIT. Sex cord-stromal cells of gonadoblastoma were immunoreactive for α-inhibin. The sex cord-stromal tumour was immunoreactive for AE1/AE3, occasionally for α-inhibin and negative for epithelial membrane antigen (EMA). The karyotype was 78, XX and PCR analysis confirmed the absence of the Y chromosome.
CONCLUSION
Based on these findings, a diagnosis of gonadoblastoma with proliferation of dysgerminoma and sex cord-stromal tumour was made. This is the first case of ovarian gonadoblastoma in a female dog.
Topics: Adult; Animals; Cell Proliferation; Dog Diseases; Dogs; Dysgerminoma; Female; Gonadoblastoma; Humans; Karyotype; Ovarian Neoplasms; Ovary; Phenotype; Proto-Oncogene Proteins c-kit; Sex Cord-Gonadal Stromal Tumors; Stromal Cells; Y Chromosome
PubMed: 31547830
DOI: 10.1186/s13048-019-0561-x -
Clinics (Sao Paulo, Brazil) 2019This review describes the germ cell neoplasms that are malignant and most commonly associated with several types of gonadal dysgenesis. The most common neoplasm is...
This review describes the germ cell neoplasms that are malignant and most commonly associated with several types of gonadal dysgenesis. The most common neoplasm is gonadoblastoma, while others including dysgerminomas, yolk-sac tumors and teratomas are rare but can occur. The purpose of this review is to evaluate the incidences of these abnormalities and the circumstances surrounding these specific tumors.According to well-established methods, a PubMed systematic review was performed, to obtain relevant studies published in English and select those with the highest-quality data.Initially, the first search was performed using gonadal dysgenesis as the search term, resulting in 12,887 PubMed papers, published, from 1945 to 2017. A second search using ovarian germ cell tumors as the search term resulted in 10,473 papers, published from 1960 to 2017. Another search was performed in Medline, using germ cell neoplasia as the search term, and this search resulted in 7,560 papers that were published between 2003 to 2016, with 245 new papers assessing gonadoblastomas.The higher incidence of germ cell tumors in gonadal dysgenesis is associated with a chromosomal anomaly that leads to the absence of germ cells in these gonads and, consequently, a higher incidence of neoplasms when these tumors are located inside the abdomen. Several hypotheses suggest that increased incidence of germ cell tumors involves all or part of the Y chromosome or different genes.
Topics: Female; Gonadal Dysgenesis; Humans; Incidence; Male; Neoplasms, Germ Cell and Embryonal; Risk Factors
PubMed: 31721911
DOI: 10.6061/clinics/2019/e408 -
BMC Cancer Nov 2020Aggressive systemic mastocytosis (ASM) is a rare malignant disease characterized by disordered mast cell accumulation in various organs. We here describe a female ASM...
BACKGROUND
Aggressive systemic mastocytosis (ASM) is a rare malignant disease characterized by disordered mast cell accumulation in various organs. We here describe a female ASM patient with a previous history of ovarian dysgerminoma.
METHODS
Molecular cytogenomic analyses were performed to elucidate an etiological link between the ASM and dysgerminoma of the patient.
RESULTS
This patient was affected by ovarian dysgerminoma which was treated by chemotherapy and surgical resection. Having subsequently been in complete remission for 2 years, she developed symptoms of ASM. A somatic D816A mutation in the KIT gene was detected in her bone marrow, which facilitated the diagnosis of ASM. Unexpectedly, this KIT D816A variant was also detected in the prior ovarian dysgerminoma sample. Whole-exome sequencing allowed us to identify a somatic nonsense mutation of the TP53 gene in the bone marrow, but not in the dysgerminoma. Microarray analysis of the patient's bone marrow revealed a copy-number-neutral loss of heterozygosity at the TP53 locus, suggestive of the homozygous nonsense mutation in the TP53 gene. In addition, the loss of heterozygosity at the TP53 locus was also detected in the dysgerminoma.
CONCLUSIONS
These results indicated that either the mast cells causing the ASM in this case had originated from the preceding ovarian dysgerminoma as a clonal evolution of a residual tumor cell, which acquired the TP53 mutation, or that both tumors developed from a common cancer stem cell carrying the KIT D816A variation.
Topics: Dysgerminoma; Female; Humans; Mastocytosis, Systemic; Middle Aged; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms
PubMed: 33246418
DOI: 10.1186/s12885-020-07653-z -
Journal of Reproductive Immunology Feb 2024Seminoma and dysgerminoma are rare testicular and ovarian germ cell tumors characterized by a significant infiltration of immune cells in the tumor microenvironment....
BACKGROUND
Seminoma and dysgerminoma are rare testicular and ovarian germ cell tumors characterized by a significant infiltration of immune cells in the tumor microenvironment. According to the failure of conventional treatments in some patients, it is crucial to identify novel prognostic and therapeutic biomarkers for these patients. The objectives of this study were to evaluate the expression of CD45RO and PD-1/PD-L1 and investigate their association with the clinicopathological characteristics of the patients.
METHODS
Immunohistochemistry was performed to assess the expression of CD45RO, PD-1, and PD-L1 in tumor-infiltrated lymphocytes (TILs), and tumor cells in 33 seminoma and 31 dysgerminoma patients. The expression levels were evaluated using a semiquantitative approach, weighted histoscore, which considers both the intensity and extent of staining.
RESULTS
All seminoma and dysgerminoma patients exhibited CD45RO expression in TILs, with 66.7 % and 90.3 % displaying high levels of expression, respectively. PD-1 expression in TILs was observed at low levels in 81.8 % and 77.4 % and at high levels in 18.2 % and 19.4 % of seminoma and dysgerminoma patients, respectively. Likewise, low expression of PD-L1 in tumor cells was detected in 63.6 % of seminoma and 61.3 % of dysgerminoma patients, while none of the patients exhibited high expression of PD-L1. In seminoma patients, a positive correlation was observed between PD-1 expression in TILs and CD45RO expression and between PD-L1 expression in tumor cells and TILs score.
CONCLUSION
The frequent infiltration of CD45RO, along with variable expression of PD-1 and PD-L1 on TILs and tumor cells, could impact the effectiveness of anti-tumor responses and immunotherapy.
Topics: Female; Humans; Male; B7-H1 Antigen; Dysgerminoma; Memory T Cells; Prognosis; Programmed Cell Death 1 Receptor; Seminoma; Testicular Neoplasms; Tumor Microenvironment; Leukocyte Common Antigens
PubMed: 38171036
DOI: 10.1016/j.jri.2023.104184 -
Gynecologic Oncology Mar 2023We previously developed preoperative and pre-chemotherapy modified versions of the male International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic model and...
OBJECTIVE
We previously developed preoperative and pre-chemotherapy modified versions of the male International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic model and assessed it in female patients with germ cell tumors (GCTs). We sought to validate these modified IGCCCG (mIGCCCG) models in a new cohort.
METHODS
We queried institutional databases for female patients with GCTs treated at Memorial Sloan Kettering Cancer Center from 1/1/1990-6/1/2020. The mIGCCCG model classifies patients with non-dysgerminomas as good, intermediate, or poor risk based on tumor markers using male IGCCCG cutoffs and absence/presence of non-pulmonary/peritoneal visceral metastasis. In dysgerminomas, good- and intermediate-risk groups are defined by absence/presence of non-pulmonary/peritoneal visceral metastasis. Progression-free survival (PFS) and overall survival (OS) were estimated for each group in the validation and combined original and validation cohorts. Associations between individual clinical factors and outcomes were evaluated.
RESULTS
Among 183 female patients with GCTs, clinical characteristics and outcomes were similar between the original (n = 93) and validation (n = 90) cohorts. In multivariable models, higher stage, older age, and non-dysgerminoma histology predicted worse PFS and OS (p < 0.05). Among 162 patients who received chemotherapy, preoperative and pre-chemotherapy mIGCCCG models were significantly associated with PFS and OS (p < 0.001 for all groups). With the preoperative model, 3-year PFS rates were 94%, 76%, and 50% in the good-, intermediate-, and poor-risk patients, respectively; OS rates were 96%, 86%, and 52%, respectively. Even within stage groups, mIGCCCG risk classifications were associated with clinical outcomes.
CONCLUSIONS
A female-specific mIGCCCG risk model effectively stratifies patients and should be incorporated into clinical trials.
Topics: Humans; Male; Female; Prognosis; Neoplasms, Germ Cell and Embryonal; Progression-Free Survival; Biomarkers, Tumor; Dysgerminoma; Ovarian Neoplasms; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36669327
DOI: 10.1016/j.ygyno.2022.12.022 -
World Journal of Clinical Oncology Oct 2022Malignant ovarian germ cell tumors (MOGCT) are rare and frequently occur in women of young and reproductive age and the oncologic and reproductive outcomes after...
BACKGROUND
Malignant ovarian germ cell tumors (MOGCT) are rare and frequently occur in women of young and reproductive age and the oncologic and reproductive outcomes after fertility-sparing surgery (FSS) for this disease are still limited.
AIM
To evaluate the oncology and reproductive outcomes of MOGCT patients who underwent FSS.
METHODS
All MOGCT patients who underwent FSS defined as the operation with a preserved uterus and at least one side of the ovary at our institute between January 2005 and December 2020 were retrospectively reviewed.
RESULTS
Sixty-two patients were recruited for this study. The median age was 22 years old and over 77% were nulliparous. The three most common histology findings were immature teratoma (32.2%), dysgerminoma (24.2%), and yolk sac tumor (24.2%). The distribution of stage was as follows; Stage I, 74.8%; stage II, 9.7%; stage III, 11.3%; and stage IV, 4.8%. Forty-three (67.7%) patients received adjuvant chemotherapy. With a median follow-up time of 96.3 mo, the 10-year progression-free survival and overall survival were 82.4% and 91%, respectively. For reproductive outcomes, of 43 patients who received adjuvant chemotherapy, 18 (41.9%) had normal menstruation, and 17 (39.5%) resumed menstruation with a median time of 4 mo. Of about 14 patients who desired to conceive, four were pregnant and delivered good outcomes. Only one case was aborted. Therefore, the successful pregnancy rate was 28.6.
CONCLUSION
The oncology and reproductive outcomes of MOGCT treated by FSS are excellent. Many patients show a long survival time with normal menstruation. However, the obstetric outcome is not quite satisfactory.
PubMed: 36337312
DOI: 10.5306/wjco.v13.i10.802 -
Diagnostic Cytopathology Nov 2019Ovarian gonadoblastoma coexisting with a dysgerminoma is extremely rare in patients with Turner syndrome (TS) and a Y chromosome. The cytological findings, including... (Review)
Review
Ovarian gonadoblastoma coexisting with a dysgerminoma is extremely rare in patients with Turner syndrome (TS) and a Y chromosome. The cytological findings, including imprint cytology, of these unusual ovarian tumors have rarely been reported. We report a rare patient with a gonadoblastoma with dysgerminoma, 3.0 × 2.0 cm in size; she was a 19-year-old woman with TS and a Y chromosome. She underwent laparoscopic bilateral gonadectomy, and the tumor was classified as stage IA (pT1aNxM0) according to the International Federation of Gynecology and Obstetrics classification system. Intraoperative imprint cytology revealed two types of neoplastic cells: small tumor cells surrounding light green-stained or eosinophilic hyaline globules with marked calcification, suspicious for gonadoblastoma; and large, round, atypical cells with abundant cytoplasm, macronucleoli, and marked lymphocytic infiltration (two-cell pattern), suspicious for dysgerminoma. The cytology results in our patient may represent the second reported results of imprint cytology describing a gonadoblastoma with dysgerminoma. They are the first reported results in a patient with TS and a Y chromosome.
Topics: Adult; Chromosomes, Human, Y; Dysgerminoma; Female; Gonadoblastoma; Humans; Ovarian Neoplasms; Turner Syndrome
PubMed: 31336030
DOI: 10.1002/dc.24282 -
Medicine Jun 2021Dysgerminoma is a rare malignant tumor of the ovary, more frequently occurring in young women. The main signs of pseudo-Meigs syndrome (PMS) are ascites and hydrothorax...
RATIONALE
Dysgerminoma is a rare malignant tumor of the ovary, more frequently occurring in young women. The main signs of pseudo-Meigs syndrome (PMS) are ascites and hydrothorax accompanying benign or malignant ovarian tumors (no fibroma or fibroma-like tumor).
PATIENT CONCERNS
A 19-year-old woman with fever and chest tightness for 2 days.
DIAGNOSES
Pectoral-abdominal computed tomography (CT) scan and contrast-enhanced magnetic resonance imaging revealed a large amount of right pleural effusion, a small amount of ascites, and a huge abdominopelvic mass measuring about 29.2cm × 11.8cm × 8.4 cm in the left ovary. The result of hydrothorax examination was consistent with the diagnosis of exudative pleural effusion. In addition, Rivalta-test showed a positive result and lactate dehydrogenase was elevated. The histopathological diagnosis was a giant germ cell tumor, which was consistent with dysgerminoma in terms of both morphology and immunophenotype. Based on these findings, a diagnosis of malignant ovarian neoplasm with PMS was made.
INTERVENTIONS
Surgical resection of the tumor was performed.
OUTCOMES
The patient recovered well after operation, and the pleural effusion and abdominal ascites vanished. No recurrence was observed during the 1-year follow-up period.
LESSONS
Ovarian dysgerminoma with PMS is a rare malignant tumor of the ovary, which often occurs in young women. It should be considered in differential diagnosis of patients with a pelvic mass, ascites and pleural effusion. Early diagnosis and surgical treatment are beneficial to prolonged survival.
Topics: Ascites; CA-125 Antigen; Diagnosis, Differential; Dysgerminoma; Female; Humans; L-Lactate Dehydrogenase; Magnetic Resonance Imaging; Meigs Syndrome; Neoplasm Staging; Ovarian Neoplasms; Ovariectomy; Pleural Effusion; Radiography, Thoracic; Tomography, X-Ray Computed; Treatment Outcome; Young Adult
PubMed: 34115045
DOI: 10.1097/MD.0000000000026319 -
Clinical Case Reports Jun 2024Fertility-sparing surgery and appropriate adjuvant chemotherapy for advanced malignant ovarian germ cell tumors have excellent survival results and promising...
KEY CLINICAL MESSAGE
Fertility-sparing surgery and appropriate adjuvant chemotherapy for advanced malignant ovarian germ cell tumors have excellent survival results and promising reproductive and obstetric outcomes.
ABSTRACT
This case report aims to demonstrate the potential feasibility and success of fertility-sparing surgery (FSS) coupled with adjuvant chemotherapy in treating advanced malignant ovarian germ cell tumor (MOGCT), focusing on pure dysgerminoma, fertility, and achieving spontaneous pregnancy. The patient was a 23-year-old female who initially presented with complaints of abdominal distension and a palpable mass and was subsequently diagnosed with advanced MOGCT. The patient provided a complete clinical and radiological response to FSS with complete surgical staging and cisplatin-based chemotherapy (bleomycin, etoposide, and cisplatin). Despite being diagnosed with advanced MOGCT and treated with FSS and adjuvant chemotherapy, she later experienced spontaneous pregnancy, giving birth to a healthy child. This case study demonstrated the potential for successful fertility preservation and pregnancy in advanced-stage MOGCT patients treated with personalized treatment approaches. Nevertheless, a broader investigation is needed to understand the relevant complex dynamics and to ascertain whether FSS with adjuvant chemotherapy could be a reliable approach in treating advanced MOGCT.
PubMed: 38827934
DOI: 10.1002/ccr3.9020