RARE DISEASE
Gestational trophoblastic disease
Gestational trophoblastic disease
Gestational trophoblastic disease
Drug discovery
0
drugs
With orphan designations
Overview
Gestational trophoblastic disease (GTD) encompasses rare pregnancy-related tumors originating from placental trophoblasts, including benign hydatidiform moles (complete/partial) and malignant forms like choriocarcinoma, invasive moles, placental-site trophoblastic tumors (PSTT), and epithelioid trophoblastic tumors (ETT) [1][6][10]. Diagnosis relies on β-hCG monitoring, imaging, and histopathology. Most cases are curable with early intervention, utilizing uterine evacuation, chemotherapy (e.g., methotrexate for low-risk, multi-agent regimens for high-risk disease), or hysterectomy for chemoresistant tumors [3][8][12]. Prognosis is excellent, with >90% cure rates even in metastatic cases [8][13].
Population
Primarily affects women at reproductive extremes (<20 or >40 years) [1][6], with higher incidence in Asia (5–10/1,000 pregnancies vs. 1–3/1,000 in North America/Europe) [2][7].
Risk factors: Prior molar pregnancy (15–20% recurrence risk after complete mole), maternal age, and Asian ethnicity [4][16].
Burden
Rare (~1/1,000 pregnancies) but causes significant morbidity (hemorrhage, metastasis) if untreated [6][14].
Requires intensive hCG surveillance for 6–12 months post-treatment to detect recurrence [3][8].
High cure rates (>90%) reduce mortality, but delayed diagnosis or chemoresistance carries poorer outcomes [4][8][17].
Therapies
Low-risk GTN: Single-agent chemotherapy (methotrexate/actinomycin D) with >85% cure rates [8][12].
High-risk/metastatic GTN: Multi-agent regimens (EMA-CO) ± surgery/radiation; hysterectomy preferred for PSTT/ETT due to chemoresistance [3][8][16].
Prophylaxis: Consider prophylactic chemotherapy for high-risk molar pregnancies to reduce persistence [3][12].
Categories: rare gynecological and obstetric diseases, rare neoplastic diseases
Research Papers
1,290 drug discovery papers about Gestational trophoblastic disease. Recent publications:
1,290 drug discovery papers about Gestational trophoblastic disease. Recent publications:
categories:
Small molecules
small molecules
2026-08-14 | Successful delivery after fertility-sparing surgery for stage I placental site trophoblastic tumor: a rare case report.
Placental site trophoblastic tumor (PSTT) is a rare subtype of gestational trophoblastic neoplasia (GTN) characterized by relative chemoresistance. The primary recommended treatment, especially for non-metastatic disease, is hysterectomy, making fertility-sparing a significant clinical challenge. There are exceedingly few reported cases of successful uterine preservation, highlighting the need for well-documented management strategies for early-stage patients with a strong desire for future fertility. We report the case of a 32-year-old woman (gravida 0, para 0) diagnosed with stage I PSTT, who initially presented with post-amenorrheic vaginal bleeding and fluctuating serum beta-human chorionic gonadotropin (β-hCG) levels and was initially misdiagnosed with an ectopic pregnancy. After unsuccessful methotrexate therapy, pelvic magnetic resonance imaging (MRI) accurately identified a focal myometrial lesion, leading to the correct diagnosis. Guided by multidisciplinary assessment and the patient's fertility desire, fertility-sparing management involving precise resection of the myometrial lesion followed by adjuvant actinomycin D/cyclophosphamide and vincristine (EMA/CO) chemotherapy was implemented to minimize recurrence risk. Following rigorous surveillance, the patient successfully conceived, delivered a healthy infant, and remained disease-free with negative β-hCG, ultrasound, and MRI findings at the 42-day postpartum check-up. This case highlights the value of pelvic MRI in facilitating the diagnosis of PSTT and suggests that fertility-sparing surgery combined with adjuvant chemotherapy may be a feasible treatment option for carefully selected patients with stage I PSTT who desire future fertility.
2026-07-25 | Impact of different EMA/CO treatment regimens in women with gestational trophoblastic neoplasia: brazilian multicenter retrospective cohort study.
To compare the clinical outcome of women with gestational trophoblastic neoplasia (GTN) treated with the conventional EMA/CO (etoposide, methotrexate, actinomycin-D, cyclophosphamide, vincristine) with those treated with the modified EM/CO regimen. Brazilian multicenter retrospective cohort study evaluated medical records of women diagnosed with GTN who were treated with the standard EMA/CO or with the modified regimen in which actinomycin-D was suppressed (EM/CO). The primary outcome was the occurrence of remission following chemotherapy treatment. Remission rate with EMA/CO was 85.3%, with 14.7% of women showing chemoresistance, while with EM/CO, the remission rate was 72.7%, with 27.3% of women chemoresistance, without statistical difference between the groups. A total of 142 women were analyzed, of whom 109 were treated with EMA/CO and 33 received EM/CO. Women who used the EM/CO had higher prevalence of invasive mole (51.5% vs. 14.7%, p<0.0001), lower prevalence of choriocarcinoma (9.1% vs. 26.6%, p=0.035), and lower prevalence of metastases (33.3% vs. 61.5%, p=0.004) compared to women who received the EMA/CO. Women with risk score ≥ 7 had higher prevalence of recurrence (61.5% vs 10.0%, p=0.005) and chemoresistance using the EM/CO (53.8% vs 10.0%, p=0.013) compared to women with score ≤ 6. The pre-treatment serum hCG levels was a moderately significant predictor (AUC: 0.77, 95%CI 0.66-0.88, p<0.0001) for identifying chemoresistance. The number of EM/CO cycles was a strong significant predictor (AUC: 0.81, 95%CI 0.66-0.96, p<0.0001) for identifying toxicity to chemotherapy. EM/CO had higher prevalence of need for second-line treatment, and chemoresistance.
2026-06-16 | Locally Advanced Invasive Mole in the Presence of Low Serum β-hCG: A Case Report.
Invasive mole is one of the most common forms of gestational trophoblastic neoplasia (GTN), characterized by hydropic chorionic villi with trophoblastic proliferation invading the myometrium. Although it usually develops after complete hydatidiform mole, occurrence following partial hydatidiform mole is uncommon. Delayed follow-up and inadequate β-human chorionic gonadotropin (β-hCG) surveillance may contribute to disease progression and severe complications. A 34-year-old woman para 2 abortus 1, presented with massive vaginal bleeding and hypovolemic shock six months after evacuation of a partial hydatidiform mole. Initial pre-evacuation β-hCG level was 1183002 mIU/mL. Due to financial constraints and inactive health insurance, post-evacuation follow-up was delayed. Serial β-hCG levels declined but remained persistently elevated for more than six months. The patient experienced continuous vaginal spotting and was diagnosed with stage I low-risk gestational trophoblastic neoplasia with a FIGO prognostic score of 4. Two weeks prior to the onset of massive bleeding, the patient had received the first cycle of single-agent methotrexate chemotherapy.Doppler ultrasonography demonstrated markedly increased myometrial vascularity suggestive of invasive mole. Despite blood transfusion, antifibrinolytic therapy, and initiation of single-agent methotrexate chemotherapy, severe vaginal bleeding persisted, resulting in profound anemia (hemoglobin 6.7 g/dL). Emergency total hysterectomy with bilateral salpingectomy was performed due to life-threatening hemorrhage. Histopathological examination confirmed invasive mole with trophoblastic invasion extending into the parametrium. No distant metastases were identified. Invasive mole following partial hydatidiform mole is rare but may lead to severe hemorrhagic complications when diagnosis and follow-up are delayed. Persistent elevation of β-hCG and abnormal uterine bleeding after molar evacuation should prompt early evaluation for gestational trophoblastic neoplasia. Multidisciplinary management, including chemotherapy, hemodynamic stabilization, and surgical intervention when indicated, is essential to achieve favorable outcomes.
2026-06-15 | Metastatic gestational trophoblastic neoplasia presenting initially as intraparenchymal and subdural hematoma: a case report.
Gestational trophoblastic neoplasia is a rare but highly chemosensitive pregnancy-related malignancy with a strong tendency for hematogenous spread and hemorrhagic metastasis. Brain involvement occurs in a minority of patients and may present as life-threatening intracranial hemorrhage. A 40-year-old Ethiopian woman presented with a sudden-onset severe headache, focal seizures, vomiting, and progressive right-sided weakness. She had a history of spontaneous abortion five months prior. Neuroimaging revealed a left frontoparietal intraparenchymal hemorrhagic mass with surrounding edema and a concomitant holohemispheric subacute subdural hematoma causing mass effect. Serum β-human chorionic gonadotropin (β-hCG) levels were elevated to 1500 IU/L. Although lower than the levels typically observed in disseminated choriocarcinoma, modest β-hCG elevations may occur in partially regressed primary lesions or in isolated metastatic disease. The patient underwent urgent craniotomy with evacuation of the subdural hematoma and resection of a hemorrhagic intraparenchymal metastatic lesion. Histopathological examination confirmed a diagnosis of metastatic choriocarcinoma. Staging evaluation revealed pulmonary and uterine involvement, consistent with International Federation of Gynecology and Obstetrics (FIGO) stage IV disease, with a World Health Organization prognostic score of 11. She received multi-agent chemotherapy with progressive neurological recovery and normalization of β-hCG levels during follow-up. Simultaneous intraparenchymal and subdural hemorrhages can represent a rare initial presentation of metastatic gestational trophoblastic neoplasia, even in the absence of gynecologic symptoms. Prompt measurement of serum β-hCG levels is essential for early diagnosis of unexplained intracranial hemorrhage in women of reproductive age. Early neurosurgical intervention combined with timely multi-agent chemotherapy can result in favorable outcomes, even in high-risk stage IV disease with brain metastasis.
2026-06-07 | Effectiveness and safety of prophylactic low-dose methotrexate in high-risk hydatidiform mole for preventing post-molar gestational trophoblastic neoplasia: a prospective comparative study from Myanmar.
To evaluate the effectiveness and safety of prophylactic low-dose methotrexate in preventing progression to gestational trophoblastic neoplasia in women with high-risk hydatidiform mole. A prospective comparative study was conducted from March 2021 to February 2023 at hospitals affiliated with the University of Medicine-1, Yangon, Myanmar. Women with high-risk hydatidiform mole were enrolled using pre-defined clinical criteria. After evacuation, treatment allocation was determined by patient preference: 51 received intra-muscular methotrexate (0.4 mg/kg/day for 5 days), and 51 were managed expectantly. All patients underwent serial serum β-human chorionic gonadotropin monitoring for six months. Multi-variable logistic regression was performed to adjust for potential confounders. A total of 102 women were included. Baseline characteristics were comparable between groups; mean age was 31.1 ± 10.3 years in the prophylactic group and 35.5 ± 10.1 years in the control group, and complete hydatidiform mole accounted for 60.8% and 64.7% of cases, respectively. Progression to gestational trophoblastic neoplasia occurred in 11/51 patients (21.6%) in the prophylactic group compared with 31/51 patients (60.8%) in the control group (p <.001). Prophylactic methotrexate was independently associated with reduced gestational trophoblastic neoplasia progression (adjusted odds ratio 0.16, 95% confidence interval 0.06 to 0.42, p <.001). Treatment-related adverse events occurred in 31/51 patients (60.8%), most commonly elevated liver enzymes (39.3%), fatigue (41.2%), and mucositis (37.3%), predominantly Common Terminology Criteria for Adverse Events grade 1 to 2. One patient developed grade 3 pancytopenia and recovered fully with supportive care. No grade 4 events or treatment-related deaths occurred. Prophylactic low-dose methotrexate was associated with a reduced risk of gestational trophoblastic neoplasia in women with high-risk hydatidiform mole. Given the non-randomized, preference-based design, these findings should be interpreted with caution. Selective use in carefully chosen high-risk patients may be beneficial, particularly in settings where reliable follow-up is limited.
cell therapies
2025-10-25 | Novel mutations of maternal effect gene thyroid hormone receptor interactor 13 involved in biparental complete hydatidiform mole.
Biparental complete hydatidiform mole (BiCHM) is a rare form of molar pregnancy, frequently associated with familial recurrence, whose mechanism was historically unclear. It is classically diploid with biparental inheritance, but manifests as a complete hydatidiform mole (CHM). Cytogenetic studies suggested a link to maternal mutations in imprinted genes NOD-like receptor family, pyrin domain containing 7 or Kelch helper domain containing 3-like within the oocyte. This case reports a novel gene association. A 43-year-old woman presented with a history of recurrent abnormal pregnancies: 2 CHM and 1 spontaneous abortion following an intracytoplasmic sperm injection (ICSI)-assisted conception. Short tandem repeat polymorphism analysis of products of conception (including both CHM and the aborted ICSI pregnancy) revealed all 3 were biparental triploids derived from the patient and her husband. Whole-exome sequencing of the patient's family identified that the patient carries compound heterozygous mutations (c.-82G > A [paternally inherited] and c.*106G > A [maternally inherited]) in the autosomal recessive gene thyroid hormone receptor interactor 13 (TRIP13), confirmed by Sanger sequencing. Given the genetic findings and history of recurrent BiCHM, ovarian donation or adoption was recommended as the treatment strategy to achieve a normal pregnancy. The genetic diagnosis was established, informing future reproductive counseling and management options. To our knowledge, this is the first report linking biallelic TRIP13 mutations to recurrent BiCHM, indicating its potential role in the pathogenesis. ICSI-assisted reproduction did not improve pregnancy outcomes. Ovarian donation or adoption was recommended.
2025-06-15 | GTN misdiagnosed as ectopic pregnancy: a 17-year retrospective cohort study.
To evaluate the effect of misdiagnosis on the chemotherapy response and prognosis of gestational trophoblastic neoplasia (GTN), and to explore strategies to enhance precision management of uncertain GTN. GTN patients misdiagnosed as ectopic pregnancies were retrospectively enrolled. GTN without misdiagnosis were randomly selected as control group at a 1:1 ratio, matching by age, WHO risk score and admission year. All patients were followed up for pregnancy, recurrence, and survival. Mann-Whitney test was used for continuous variables. Categorical variables were assessed using the Chi-square test or Fisher's exact test. Among 35 misdiagnosed cases, high-risk GTN accounted for 57.1 %. Antecedent nonmolar pregnancy in misdiagnosed group was 88.6 %. Pretreatment human chorionic gonadotropin (hCG) was lower (3477 vs 18,121 IU/L) while recurrence rate was significantly higher in misdiagnosed group than in control group (28.6 % vs 5.7 %, p = 0.011). The resistance rate showed an increasing trend in misdiagnosed group (22.9 % vs 14.3 %, p = 0.356). For subgroup analysis, the resistance rate was increased in group A (treated with methotrexate) than group B (without methotrexate), while decreased in patients with lesion resection (group C) than without resection (group D), especially for low-risk patients. Histopathological misdiagnosis for antecedent pregnancy and GTN in primary hospitals were 2 and 6 cases respectively. GTN after nonmolar pregnancy with low hCG are prone to be misdiagnosed, which might lead to increased WHO risk scores, resistance, and relapse rates. Surgical intervention, especially lesion resection instead of methotrexate, is recommended for atypical GTN.
2025-05-05 | Is gestational trophoblastic neoplasia more common among women with recurrent hydatidiform moles and biallelic NLRP7 mutations? a 17-years prospective study from India.
Recurrent hydatidiform moles (RHM) is a rare entity defined by the occurrence of two or more hydatidiform moles (HM) in a woman. We present data of women with RHM from a tertiary care institute in North India with respect to the incidence of Gestational Trophoblastic Neoplasia (GTN), subsequent reproductive outcome and genetic analysis in this cohort. Women who presented with RHM and no prior live birth were enrolled from 2005 to 2022 and analysed for the presence of pathogenic or likely pathogenic (P/LP) variants in genes responsible for RHM. They were followed-up for occurrence of post-molar GTN as per FIGO and WHO guidelines, and subsequent reproductive outcomes. Of the 23 women with RHM, 22 (95.6 %) had biallelic P/LP variants in three genes, 20 in NLRP7 (87 %), one in KHDC3L (4 %), and one in TOP6BL (4 %). Of the 20 women with NLRP7 variants, 10 (50 %) developed GTN, mostly low-risk, which is approximately 2 to 3 times higher than the rate of GTN among women with sporadic HM at similar ages. Three of these women had recurrent GTN. Among the 22 women with biallelic P/LP variants, only one had a spontaneous live birth, and four underwent IVF with donated ova, of whom three had live births. Only one woman was negative for recessive causative variants in the known genes or any novel gene and she subsequently had two spontaneous live births. Our data indicate a high incidence of biallelic P/LP NLRP7 variants among Indian women with RHM and no live birth. These women appeared to be at a higher risk for developing GTN and had a very low chance of a spontaneous live birth, and these two concerns may be mitigated by avoiding a spontaneous pregnancy and having donor ovum IVF. All women with RHM should have genetic testing and counseling specifically due to their higher risk of GTN.
2024-10-11 | The role of extracellular vesicles in the pathogenesis of gynecological cancer.
Gynecological cancer, the most common form of cancers in women worldwide, initiates in the reproductive organs of females. More often, the common treatment measures, i.e. surgery, radiation, and medical oncology are found to be unsuccessful in the treatment of gynecological tumors. Emerging evidence indicates that extracellular vesicles (EVs) play a significant role in the pathogenesis of gynecological cancers by distinct mechanisms. The present review highlights how EVs contribute to the progression of different types of gynecological cancers such as cervical cancer, endometrial cancer, ovarian cancer, vaginal cancer, uterine sarcoma, gestational trophoblastic disease (GTD), and vulvar cancer. The primary focus is to understand how EVs' cargo alters the phenotypic response of the recipient cells, thereby contributing to the progression of the disease, thus can be considered as a prognostic and diagnostic biomarker. A brief discussion on the role of EVs in the diagnosis and prognosis of different gynecological cancer types is also highlighted. Targeting the biogenesis of the EVs, their inside cargo, and EVs uptake by the recipient cells could be a potential therapeutic approach in the treatment of gynecological cancer beside conventional therapeutic means.
2024-06-04 | Surgical Management of Gestational Trophoblastic Disease.
Gestational trophoblastic disease (GTD) is a rare pregnancy-related condition consisting of premalignant and malignant forms arising from proliferation of trophoblastic cells. The malignant forms are collectively referred to as gestational trophoblastic neoplasia (GTN) and are highly sensitive to chemotherapy. However, surgical procedures remain indispensable in the diagnosis and treatment of GTD. The aim of this review was to summarize surgical interventions in the treatment of GTD and GTN. We reviewed indications, efficacy, possible complications, and oncological outcomes of surgery. Three searches were performed in the databases of PubMed, Embase, and the Cochrane Library to create an up-to-date overview of existing literature on the following subjects: (1) the role of primary hysterectomy in GTD and GTN; (2) the role of second curettage in GTD and GTN; (3) fertility sparing surgery in GTN; (4) surgical management of metastases. Included articles originated from the time period 1952-2022. Articles written in English, Spanish, and French were included. Thirty-eight articles were found and selected. Surgical evacuation through suction curettage is most used and advised in the treatment of GTD. A second curettage could be beneficial in patients with low hCG levels and low FIGO scores. In women who have completed their families, primary hysterectomy might be considered as the risk of subsequent GTN is lower than after suction curettage. In case of the rare forms of GTN (epithelioid trophoblastic tumor or placental site trophoblastic tumor) surgical tumor resection remains the most important step in treatment. Data on fertility sparing surgery in GTN are scarce and this treatment should be considered experimental. Surgery remains an important part of treatment of GTD and is sometimes indispensable to achieve curation. Further collection of evidence is needed to determine treatment steps.
antibodies
2026-07-30 | Gestational Trophoblastic Diseases. An Overview of Patients visiting Sheikh Zayed Medical Hospital, Rahim Yar Khan
Background: Gestational trophoblastic disease is an important obstetric condition which if untreated, can result in serious and harmful consequences. Objective of this study was to determine incidence and pattern of gestational trophoblastic disease in tertiary care hospital of Rahim Yar khan. Methods: This prospective observational cohort study was conducted at Sheikh Zayed Medical Hospital, Rahim Yar Khan, from January 2019 to December 2022. Patients presented with gestational amenorrhea and vaginal bleeding were sus-pected to be cases of molar pregnancy based on certain distinct clinical factors. These indicators included a large-for-date symphysio-fundal height (SFH), a snow storm appearance on ultrasonography, and significantly higher serum β-hCG levels. Data for these specific cases was collected from molar pregnancy registers maintained in Obstetrics and Gynecology de-partment of Sheikh Zayed Medical Hospital, Rahim Yar Khan. Final diagnosis of molar pregnancy was confirmed by histo-pathology of the tissue removed from uterine cavity by suction and evacuation. Results: A total of 33,494 pregnant women were admitted during the study period. Among this population, 197 were diag-nosed with a molar pregnancy, representing a 0.58% rate. This equates to an overall incidence of 5.8 per 1,000 obstetric admission. Complete hydatidiform mole was the most common type, diagnosed in 127 females (64.4%). Partial mole oc-curred in 58 females (29.4%), while choriocarcinoma was found in 12 females (6.1%). Among 12 women with choriocarci-noma, four presented with pulmonary metastasis, received multiagent chemotherapy in liaison with oncology department.Conclusion: High sensitivity pelvic ultrasonography may have led to early detection of abnormal pregnancies, before we can detect classical symptoms or identify patients with advanced disease.
2026-07-20 | Gynecologic Cancer—A Global Platform for Inclusive Collaboration and Excellence in Gynecologic Oncology
Gynecologic Cancers—including ovarian, fallopian tube, endometrial, cervical, vulvar, as well as placental and gestational trophoblastic diseases—remain a major global health burden despite decades of scientific progress [...]
2026-06-26 | A Case of Placental Site Trophoblastic Tumour That Mimicked Missed Miscarriage.
Background and Clinical Significance: Placental site trophoblastic tumour (PSTT) is a malignant tumour of the implantation site intermediate trophoblasts. It has historically been described using terms such as atypical chorioepithelioma, atypical choriocarcinoma, syncytioma, and chorioepitheliosis. It belongs to one of the heterogeneous spectrums of gestational trophoblastic disease. It accounts for about 0.25 to 5% of all gestational trophoblastic neoplasia. The typical clinical presentation is alternating menorrhagia and amenorrhea, mildly elevated β-hCG, and radiological findings of a uterine mass. Case Presentation: A 32-year-old woman presented with a history of intermittent menorrhagia and amenorrhea, with a persistent mildly raised β-hCG level. Ultrasonography showed a hypoechoic lesion on the right side of the posterior wall of the uterus. She was diagnosed with a missed miscarriage, and an evacuation of the products of conception was performed. Histologically, the tissue fragments comprised cords and sheets of atypical intermediate trophoblast cells, with characteristic features of myometrial smooth muscle infiltration, vascular invasion, and vascular wall replaced by the neoplastic cells. Immunohistochemically, these cells are positive for β-hCG and GATA3, while negative for P63. Conclusions: PSTT is a rare form of gestational trophoblastic neoplasia. Early recognition of PSTT is essential because its clinical presentation may mimic benign pregnancy-related conditions, and diagnosis relies heavily on histopathological and immunohistochemical evaluation.
2026-06-22 | Refractory ultra-high-risk Choriocarcinoma achieving complete response to intensive multi-agent and intrathecal chemotherapy and anti-PD-L1 therapy.
Background: Choriocarcinoma is a highly aggressive gestational trophoblastic neoplasm. Patients with ultra-high-risk disease (FIGO score ≥ 13) and brain metastases face cure rates of only 50-80% and require intensive multimodal therapy. Case: We present the case of a 37-year-old woman with stage IV choriocarcinoma (FIGO score 14 ultra-high-risk) who presented with lung and brain metastases. Despite an initial response to standard chemotherapy, she experienced early relapse with progressive central nervous system disease. She received salvage treatment with intensive multi-agent escalated EP chemotherapy, intrathecal methotrexate, and pembrolizumab (anti-PD-1) introduced at cycle three and stereotactic radiosurgery for residual CNS disease, achieving a complete radiological and biochemical response sustained for over one year. Conclusion: This case highlights the challenges of managing ultra-high-risk gestational trophoblastic neoplasia and underscores the importance of multidisciplinary collaboration. The complete response achieved with the addition of pembrolizumab to dose-intensified, intrathecal, and high-dose chemotherapy supports the use of immune checkpoint inhibition in the management of refractory ultra-high-risk GTN.
2026-05-15 | A Rare Case of Primary Pulmonary Choriocarcinoma Metastasizing to the Kidney: Diagnostic and Therapeutic Complexities.
Choriocarcinoma is a highly aggressive malignant tumor composed primarily of cytotrophoblast and syncytiotrophoblast cells without villi and is characterized by beta-human chorionic (beta-hCG) gonadotropin production. Although most cases are of gestational origin, rare non-gestational choriocarcinomas may arise from pluripotent germ cells in extragenital locations, independently of pregnancy. Primary pulmonary choriocarcinoma is extremely rare, and kidney metastasis has only exceptionally been reported in the literature. We present the case of a 43-year-old patient with this unusual presentation. The diagnostic process began with a suspected implantation of unknown location and culminated in the final histopathological diagnosis based on lobectomy and nephrectomy specimens, including molecular genetic identification of the pulmonary tumor. Following thoracic and renal surgery, the patient received adjuvant chemotherapy and immunotherapy with anti-PD-1 monoclonal antibodies. This case highlighted the diagnostic challenges posed by primary pulmonary choriocarcinoma with renal metastasis, an exceptionally rare clinical entity. Ongoing follow-up includes regular imaging studies and beta-hCG monitoring.
oligonucleotides
2024-02-19 | Twist-1 Stimulates the Malignant Behaviors of Hydatidiform Mole via the PI3K/AKT Pathway
Background: Hydatidiform mole (HM) is a common pregnancy disease among women of gestational age. Twist-related protein 1 (Twist-1) is involved in the development of various tumors, but its role in HM is poorly defined. This study aimed to explore Twist-1 expression and its biological function in HM cells. Methods: Twist-1 expression in HM was detected by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). The effects of silencing Twist-1 on choriocarcinoma (CCA) cell proliferation were detected by cell counting kit-8 (CCK-8) and clone formation assays. CCA cell migration and invasion were detected through transwell assay. Western blot was used to detect epithelial–mesenchymal transition (EMT) and the expression of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway-related proteins. Results: Twist-1 expression was upregulated in HM tissues (p < 0.001) and CCA cells (p < 0.01). Twist-1 silencing inhibited proliferation of BeWo and JAR cells (p < 0.01, p < 0.05) as shown by CCK-8 assay (p < 0.01) and clone formation assays (p < 0.01, p < 0.05). Twist-1 silencing inhibited the migration (p < 0.01) and invasion activity (p < 0.01, p < 0.05) of BeWo and JAR cells. Western blot results showed that Twist-1 silencing promoted E-cadherin (p < 0.01) expression, and inhibited N-cadherin (p < 0.01, p < 0.05) and vimentin (p < 0.01, p < 0.05) expression in BeWo and JAR cells. Twist-1 downregulation decreased protein levels of p-PI3K (p < 0.01) and p-AKT (p < 0.01, p < 0.05) in BeWo and JAR cells. Conclusions: Silencing Twist-1 inhibits the malignant behavior of CCA cells, which may play a part by inhibiting the EMT process and the PI3K/AKT pathway.
2022-10-18 | METTL3 m6A-dependently promotes miR-21-5p maturation to accelerate choriocarcinoma progression via the HIF1AN-induced inactivation of the HIF1A/VEGF pathway.
Gestational choriocarcinoma is a highly malignant neoplastic disease derived from pathological changes in trophoblastic cells. Recent evidences have shown that N6-methyladenosine (m6A) modifications play important role in modulating the development of multiple cancers, but the detailed mechanisms by which m6A-mediated choriocarcinoma progression have not been fully delineated. This study aimed to investigate the role of m6A in choriocarcinoma and reveal its underlying molecular mechanisms. The expression of METTL3, miR-21-5p and HIF1AN was detected using RT-qPCR in tissues and cells. The protein expression of METTL3, HIF1AN, HIF1A and VEGF were measured by western blot. The luciferase reporter assays and RNA immunoprecipitation (RIP) were used to verify the relationship between miR-21-5p and HIF1AN. The CCK-8, colony formation and transwell assays were used to detected cell proliferation and cell migration, respectively. Here, we demonstrated that the m6A methyltransferase-like 3 (METTL3) was aberrantly high-expressed in the clinical choriocarcinoma tissues and choriocarcinoma cell lines compared to the corresponding normal counterparts. The following functional experiments verified that silencing of METTL3 suppressed cell proliferation, migration, epithelial-mesenchymal transition (EMT) and tumorigenesis in vitro and in vivo to hamper the aggressiveness of choriocarcinoma. Next, the mechanical experiments confirmed that METTL3 promoted the maturation of miR-21-5p in an m6A-dependent manner, and elevated miR-21-5p subsequently degraded its downstream hypoxia-inducible factor asparagine hydroxylase (HIF1AN) by targeting its 3' untranslated regions (3'-UTR), resulting in the activation of the tumor-promoting HIF1A/VEGF pathway. Finally, the rescuing experiments verified that METTL3 ablation-induced inhibitory effects on the malignant phenotypes in choriocarcinoma were all abrogated by both miR-21-5p overexpression and HIF1AN downregulation. Collectively, this study firstly reported the involvement of the METTL3/m6A/miR-21-5p/HIF1AN signaling cascade in regulating the progression of choriocarcinoma, which provided novel biomarkers for the diagnosis and treatment of this disease.
2022-06-06 | CBR3-AS1 Accelerates the Malignant Proliferation of Gestational Choriocarcinoma Cells by Stabilizing SETD4.
Gestational choriocarcinoma (GC) is a rare malignant gestational trophoblastic tumor. Long noncoding RNA (lncRNA) CBR3 antisense RNA 1 (CBR3-AS1) has been reported to serve as a critical oncogene and facilitate tumor progression. Besides, we found that CBR3-AS1 is implicated in GC progression. Gene and protein expression was detected via quantitative reverse transcription PCR (RT-qPCR) and western blot analyses, respectively. CCK-8 assay and colony formation assay were performed to assess cell proliferative abilities while flow cytometry analysis was applied for cell cycle and apoptosis. To analyze the specific mechanism among CBR3-AS1, SET domain containing 4 (SETD4), and polypyrimidine tract binding protein 1 (PTBP1), RNA binding protein immunoprecipitation (RIP), RNA pulldown, and mRNA stability assays were conducted. CBR3-AS1 was markedly upregulated in GC cells, and its downregulation suppressed cell proliferation, induced cell cycle arrest, but promoted cell apoptosis in GC. SETD4 was determined as the downstream mRNA of CBR3-AS1 and positively regulated by CBR3-AS1 in GC cells. Furthermore, CBR3-AS1 could interact with its RNA binding protein (RBP) PTBP1, thereby stabilizing SETD4 mRNA. Rescue assays verified that CBR3-AS1 facilitates GC cell malignant proliferation via SETD4. CBR3-AS1 accelerates the malignant proliferation of GC cells via stabilizing SETD4.
2022-03-04 | Prediction of Neoplastic Transformation of Hydatidiform Mole: Current Evidence.
Gestational trophoblastic disease is not an uncommonly encountered pathology in clinical practice. The rate of post-molar neoplastic transformation is around 5-20% with higher rates after complete versus partial molar pregnancies. Recently, a role for molecular and genetic markers in the prediction of neoplastic transformation has emerged. We read with interest the article by St. Laurent et al. published in this issue of Reproductive Sciences. The authors compared miRNA profiles between complete hydatidiform moles (CHMs) and pre-gestational trophoblastic neoplasia CHM samples at three distinct tropho-miRNA clusters, 14q32, C19MC, and miR-371-3, as well as the expression of the contiguous DLK1, DIO3, and RTL1 genes. They found significant differences in expression of the 14q32 miRNA cluster and a fivefold decrease in protein expression of DIO3 but no difference in DIO3 mRNA expression. We reviewed the literature for similar studies looking at predictive tools for neoplastic transformation. We encourage future randomized controlled trials using these 2 novel risk predictors postulated by St. Laurent et al. to validate and guide future prophylactic chemotherapy for prevention of post-molar GTN.
2022-03-04 | miR-30a targets STOX2 to increase cell proliferation and metastasis in hydatidiform moles via ERK, AKT, and P38 signaling pathways
Abstract Background A hydatidiform mole is a condition caused by abnormal proliferation of trophoblastic cells. MicroRNA miR-30a acts as a tumor suppressor gene in most tumors and participates in the development of various cancers. However, its role in hydatidiform moles is not clear. Methods Quantitative real-time reverse transcription PCR was used to verify the expression level of miR-30a and STOX2 (encoding storkhead box 2). Flow cytometry assays were performed to detect the cell cycle in cell with different expression levels of miR-30a and STOX2 . Cell Cycle Kit-8, 5-ethynyl-2′-deoxyuridine, and colony formation assays were used to detect cell proliferation and viability. Transwell assays was used to test cell invasion and migration. Dual-luciferase reporter assays and western blotting were used to investigate the potential mechanisms involved. Result Low miR-30a expression promoted the proliferation, migration, and invasion of trophoblastic cells (JAR and HTR-8). Dual luciferase assays confirmed that STOX2 is a target of miR-30a and resisted the effect of upregulated miR-30a in trophoblastic cells. In addition, downregulation of STOX2 by miR-30a could activate ERK, AKT, and P38 signaling pathways. These results revealed a new mechanism by which ERK, AKT, and P38 activation by miR-30a/STOX2 results in excessive proliferation of trophoblast cells in the hydatidiform mole. Conclusions In this study, we found that miR-30a plays an important role in the development of the hydatidiform mole. Our findings indicate that miR-30a might promote the malignant transformation of human trophoblastic cells by regulating STOX2 , which strengthens our understanding of the role of miR-30a in regulating trophoblastic cell transformation.
other
2024-05-02 | Organ-preserving treatment of a patient with a trophoblastic tumor of the placental bed (clinical observation and literature review)
Placental site trophoblastic tumor (PSTT) is а rare form of gestational trophoblastic neoplasia (GTN), accounting 0,2 % of total cases of GTN. PSTTs occur in women of childbearing age and most of them have strong desire to preserve fertility. PSSTs are tumors with unpredictable biological behavior, high chemo-resistance and possibly fatal outcome in case of metastatic disease. Hysterectomy is the primary treatment of choice in early disease. We report a rare clinical case of fertility sparing treatment for PSTT.
2024-01-25 | Oncostatin M and STAT3 Signaling Pathways Support Human Trophoblast Differentiation by Inhibiting Inflammatory Stress in Response to IFNγ and GM-CSF
Interleukin-6 (IL-6) superfamily cytokines play critical roles during human pregnancy by promoting trophoblast differentiation, invasion, and endocrine function, and maintaining embryo immunotolerance and protection. In contrast, the unbalanced activity of pro-inflammatory factors such as interferon gamma (IFNγ) and granulocyte–macrophage colony-stimulating factor (GM-CSF) at the maternal–fetal interface have detrimental effects on trophoblast function and differentiation. This study demonstrates how the IL-6 cytokine family member oncostatin M (OSM) and STAT3 activation regulate trophoblast fusion and endocrine function in response to pro-inflammatory stress induced by IFNγ and GM-CSF. Using human cytotrophoblast-like BeWo (CT/BW) cells, differentiated in villous syncytiotrophoblast (VST/BW) cells, we show that beta-human chorionic gonadotrophin (βhCG) production and cell fusion process are affected in response to IFNγ or GM-CSF. However, those effects are abrogated with OSM by modulating the activation of IFNγ-STAT1 and GM-CSF-STAT5 signaling pathways. OSM stimulation enhances the expression of STAT3, the phosphorylation of STAT3 and SMAD2, and the induction of negative regulators of inflammation (e.g., IL-10 and TGFβ1) and cytokine signaling (e.g., SOCS1 and SOCS3). Using STAT3-deficient VST/BW cells, we show that STAT3 expression is required for OSM to regulate the effects of IFNγ in βhCG and E-cadherin expression. In contrast, OSM retains its modulatory effect on GM-CSF-STAT5 pathway activation even in STAT3-deficient VST/BW cells, suggesting that OSM uses STAT3-dependent and -independent mechanisms to modulate the activation of pro-inflammatory pathways IFNγ-STAT1 and GM-CSF-STAT5. Moreover, STAT3 deficiency in VST/BW cells leads to the production of both a large amount of βhCG and an enhanced expression of activated STAT5 induced by GM-CSF, independently of OSM, suggesting a key role for STAT3 in βhCG production and trophoblast differentiation through STAT5 modulation. In conclusion, our study describes for the first time the critical role played by OSM and STAT3 signaling pathways to preserve and regulate trophoblast biological functions during inflammatory stress.
2024-01-16 | Impact of molecular genotyping on the diagnosis and treatment of human chorionic gonadotropin-producing tumors.
To assess the use of molecular genotyping to accurately diagnose and treat human chorionic gonadotropin (hCG)-producing tumors and to evaluate the discriminating capacity of molecular testing on prognosis and overall survival. We conducted a retrospective descriptive study of patients registered with the French Reference Center for Trophoblastic Disease between 1999 and 2021. We included all patients with hCG-producing tumors for whom results of molecular genotyping were available. Fifty-five patients with molecular genotyping were included: 81.2 % (n = 45) had tumors of gestational origin, 12.7 % (n = 7) of non-gestational origin and 5.5 % (n = 3) of undetermined origin. The results of molecular genotyping influenced the treatment decisions for 17 % of patients in this cohort. Overall survival was 93.3 % for patients with gestational tumors (after a median follow-up of 74 months) compared to 71.4 % for patients with non-gestational tumors (after a median follow-up of 23 months). In atypical presentations of hCG-producing tumors, molecular genotyping is a valuable tool to guide diagnosis and tailor treatment recommendations.
2023-02-15 | Current chemotherapeutic options for the treatment of gestational trophoblastic disease.
Gestational trophoblastic neoplasia (GTN) is a rare tumor that arises from trophoblastic tissues with high remission rates after chemotherapy treatment. GTN can develop from any gestational events, such as miscarriage, ectopic pregnancy, and preterm/term pregnancy, but is more frequent after hydatidiform mole. The sensitivity of this tumor to chemotherapy and the presence of an exceptional tumor marker allow high remission rates, especially when patients are treated in referral centers. Observational, retrospective, prospective, systematic reviews, and meta-analysis studies focusing on GTN treatment. We searched PubMed, Medline, and the Library of Congress from January 1965 to May 2022. Early GTN diagnosis allows low-toxic and highly effective treatment. Even multimetastatic disease has high rates of remission with multiagent regimen chemotherapy. Surgery is reserved for uterine disease in patients who have completed childbearing, in cases of chemoresistance to multiagent regimens or in the rare cases of placental site trophoblastic tumor or epithelioid trophoblastic tumor. While resistance is managed by salvage chemotherapy, cases with limited clinical response to sequential regimens have been successfully treated with immunotherapy.
2022-05-09 | The immune microenvironment of the hydatidiform mole.
Gestational trophoblastic diseases (GTDs) are a heterogeneous group of lesions, the most frequent being the hydatidiform mole (HM). HMs are usually cured after surgical treatment or after chemotherapy in the case of a persistent trophoblastic activity. Immunotherapy could be an interesting alternative as a first-line or second-line treatment. However, only a few studies have explored the immune microenvironment of HMs. In the present retrospective study including 19 complete and 17 partial moles, we examined the composition of the immune cell microenvironment by immunohistochemistry using the following antibodies: CD4, CD8, CD56, PD-L1, S100, CD83, CD207, CD123, CD1a, CD11c, CD163, PAX5, and MUM1. In the decidual cells compartment, CD11c+ cells were the predominant population, followed by CD4+ cells, CD56+ NK cells, CD163+ macrophages, and CD8+ T lymphocytes.In the endometrial glands compartment, CD11c+ cells were the predominant population, followed by CD4+ cells, CD56+ NK cells, and CD8+ T lymphocytes. In the villi compartment, the predominant immune cells were CD4+ cells, followed by CD163+ macrophages and CD11c+ cells. Statistically significant differences were observed between partial and complete moles in all three compartments. The immune microenvironment of HMs is immunosuppressive, but it differs between complete and partial moles, the latter having a higher infiltrate of cells with phenotypes suggestive of immunosuppressive activities.
small molecules
2026-08-14 | Successful delivery after fertility-sparing surgery for stage I placental site trophoblastic tumor: a rare case report.
Placental site trophoblastic tumor (PSTT) is a rare subtype of gestational trophoblastic neoplasia (GTN) characterized by relative chemoresistance. The primary recommended treatment, especially for non-metastatic disease, is hysterectomy, making fertility-sparing a significant clinical challenge. There are exceedingly few reported cases of successful uterine preservation, highlighting the need for well-documented management strategies for early-stage patients with a strong desire for future fertility. We report the case of a 32-year-old woman (gravida 0, para 0) diagnosed with stage I PSTT, who initially presented with post-amenorrheic vaginal bleeding and fluctuating serum beta-human chorionic gonadotropin (β-hCG) levels and was initially misdiagnosed with an ectopic pregnancy. After unsuccessful methotrexate therapy, pelvic magnetic resonance imaging (MRI) accurately identified a focal myometrial lesion, leading to the correct diagnosis. Guided by multidisciplinary assessment and the patient's fertility desire, fertility-sparing management involving precise resection of the myometrial lesion followed by adjuvant actinomycin D/cyclophosphamide and vincristine (EMA/CO) chemotherapy was implemented to minimize recurrence risk. Following rigorous surveillance, the patient successfully conceived, delivered a healthy infant, and remained disease-free with negative β-hCG, ultrasound, and MRI findings at the 42-day postpartum check-up. This case highlights the value of pelvic MRI in facilitating the diagnosis of PSTT and suggests that fertility-sparing surgery combined with adjuvant chemotherapy may be a feasible treatment option for carefully selected patients with stage I PSTT who desire future fertility.
2026-07-25 | Impact of different EMA/CO treatment regimens in women with gestational trophoblastic neoplasia: brazilian multicenter retrospective cohort study.
To compare the clinical outcome of women with gestational trophoblastic neoplasia (GTN) treated with the conventional EMA/CO (etoposide, methotrexate, actinomycin-D, cyclophosphamide, vincristine) with those treated with the modified EM/CO regimen. Brazilian multicenter retrospective cohort study evaluated medical records of women diagnosed with GTN who were treated with the standard EMA/CO or with the modified regimen in which actinomycin-D was suppressed (EM/CO). The primary outcome was the occurrence of remission following chemotherapy treatment. Remission rate with EMA/CO was 85.3%, with 14.7% of women showing chemoresistance, while with EM/CO, the remission rate was 72.7%, with 27.3% of women chemoresistance, without statistical difference between the groups. A total of 142 women were analyzed, of whom 109 were treated with EMA/CO and 33 received EM/CO. Women who used the EM/CO had higher prevalence of invasive mole (51.5% vs. 14.7%, p<0.0001), lower prevalence of choriocarcinoma (9.1% vs. 26.6%, p=0.035), and lower prevalence of metastases (33.3% vs. 61.5%, p=0.004) compared to women who received the EMA/CO. Women with risk score ≥ 7 had higher prevalence of recurrence (61.5% vs 10.0%, p=0.005) and chemoresistance using the EM/CO (53.8% vs 10.0%, p=0.013) compared to women with score ≤ 6. The pre-treatment serum hCG levels was a moderately significant predictor (AUC: 0.77, 95%CI 0.66-0.88, p<0.0001) for identifying chemoresistance. The number of EM/CO cycles was a strong significant predictor (AUC: 0.81, 95%CI 0.66-0.96, p<0.0001) for identifying toxicity to chemotherapy. EM/CO had higher prevalence of need for second-line treatment, and chemoresistance.
2026-06-16 | Locally Advanced Invasive Mole in the Presence of Low Serum β-hCG: A Case Report.
Invasive mole is one of the most common forms of gestational trophoblastic neoplasia (GTN), characterized by hydropic chorionic villi with trophoblastic proliferation invading the myometrium. Although it usually develops after complete hydatidiform mole, occurrence following partial hydatidiform mole is uncommon. Delayed follow-up and inadequate β-human chorionic gonadotropin (β-hCG) surveillance may contribute to disease progression and severe complications. A 34-year-old woman para 2 abortus 1, presented with massive vaginal bleeding and hypovolemic shock six months after evacuation of a partial hydatidiform mole. Initial pre-evacuation β-hCG level was 1183002 mIU/mL. Due to financial constraints and inactive health insurance, post-evacuation follow-up was delayed. Serial β-hCG levels declined but remained persistently elevated for more than six months. The patient experienced continuous vaginal spotting and was diagnosed with stage I low-risk gestational trophoblastic neoplasia with a FIGO prognostic score of 4. Two weeks prior to the onset of massive bleeding, the patient had received the first cycle of single-agent methotrexate chemotherapy.Doppler ultrasonography demonstrated markedly increased myometrial vascularity suggestive of invasive mole. Despite blood transfusion, antifibrinolytic therapy, and initiation of single-agent methotrexate chemotherapy, severe vaginal bleeding persisted, resulting in profound anemia (hemoglobin 6.7 g/dL). Emergency total hysterectomy with bilateral salpingectomy was performed due to life-threatening hemorrhage. Histopathological examination confirmed invasive mole with trophoblastic invasion extending into the parametrium. No distant metastases were identified. Invasive mole following partial hydatidiform mole is rare but may lead to severe hemorrhagic complications when diagnosis and follow-up are delayed. Persistent elevation of β-hCG and abnormal uterine bleeding after molar evacuation should prompt early evaluation for gestational trophoblastic neoplasia. Multidisciplinary management, including chemotherapy, hemodynamic stabilization, and surgical intervention when indicated, is essential to achieve favorable outcomes.
2026-06-15 | Metastatic gestational trophoblastic neoplasia presenting initially as intraparenchymal and subdural hematoma: a case report.
Gestational trophoblastic neoplasia is a rare but highly chemosensitive pregnancy-related malignancy with a strong tendency for hematogenous spread and hemorrhagic metastasis. Brain involvement occurs in a minority of patients and may present as life-threatening intracranial hemorrhage. A 40-year-old Ethiopian woman presented with a sudden-onset severe headache, focal seizures, vomiting, and progressive right-sided weakness. She had a history of spontaneous abortion five months prior. Neuroimaging revealed a left frontoparietal intraparenchymal hemorrhagic mass with surrounding edema and a concomitant holohemispheric subacute subdural hematoma causing mass effect. Serum β-human chorionic gonadotropin (β-hCG) levels were elevated to 1500 IU/L. Although lower than the levels typically observed in disseminated choriocarcinoma, modest β-hCG elevations may occur in partially regressed primary lesions or in isolated metastatic disease. The patient underwent urgent craniotomy with evacuation of the subdural hematoma and resection of a hemorrhagic intraparenchymal metastatic lesion. Histopathological examination confirmed a diagnosis of metastatic choriocarcinoma. Staging evaluation revealed pulmonary and uterine involvement, consistent with International Federation of Gynecology and Obstetrics (FIGO) stage IV disease, with a World Health Organization prognostic score of 11. She received multi-agent chemotherapy with progressive neurological recovery and normalization of β-hCG levels during follow-up. Simultaneous intraparenchymal and subdural hemorrhages can represent a rare initial presentation of metastatic gestational trophoblastic neoplasia, even in the absence of gynecologic symptoms. Prompt measurement of serum β-hCG levels is essential for early diagnosis of unexplained intracranial hemorrhage in women of reproductive age. Early neurosurgical intervention combined with timely multi-agent chemotherapy can result in favorable outcomes, even in high-risk stage IV disease with brain metastasis.
2026-06-07 | Effectiveness and safety of prophylactic low-dose methotrexate in high-risk hydatidiform mole for preventing post-molar gestational trophoblastic neoplasia: a prospective comparative study from Myanmar.
To evaluate the effectiveness and safety of prophylactic low-dose methotrexate in preventing progression to gestational trophoblastic neoplasia in women with high-risk hydatidiform mole. A prospective comparative study was conducted from March 2021 to February 2023 at hospitals affiliated with the University of Medicine-1, Yangon, Myanmar. Women with high-risk hydatidiform mole were enrolled using pre-defined clinical criteria. After evacuation, treatment allocation was determined by patient preference: 51 received intra-muscular methotrexate (0.4 mg/kg/day for 5 days), and 51 were managed expectantly. All patients underwent serial serum β-human chorionic gonadotropin monitoring for six months. Multi-variable logistic regression was performed to adjust for potential confounders. A total of 102 women were included. Baseline characteristics were comparable between groups; mean age was 31.1 ± 10.3 years in the prophylactic group and 35.5 ± 10.1 years in the control group, and complete hydatidiform mole accounted for 60.8% and 64.7% of cases, respectively. Progression to gestational trophoblastic neoplasia occurred in 11/51 patients (21.6%) in the prophylactic group compared with 31/51 patients (60.8%) in the control group (p <.001). Prophylactic methotrexate was independently associated with reduced gestational trophoblastic neoplasia progression (adjusted odds ratio 0.16, 95% confidence interval 0.06 to 0.42, p <.001). Treatment-related adverse events occurred in 31/51 patients (60.8%), most commonly elevated liver enzymes (39.3%), fatigue (41.2%), and mucositis (37.3%), predominantly Common Terminology Criteria for Adverse Events grade 1 to 2. One patient developed grade 3 pancytopenia and recovered fully with supportive care. No grade 4 events or treatment-related deaths occurred. Prophylactic low-dose methotrexate was associated with a reduced risk of gestational trophoblastic neoplasia in women with high-risk hydatidiform mole. Given the non-randomized, preference-based design, these findings should be interpreted with caution. Selective use in carefully chosen high-risk patients may be beneficial, particularly in settings where reliable follow-up is limited.
cell therapies
2025-10-25 | Novel mutations of maternal effect gene thyroid hormone receptor interactor 13 involved in biparental complete hydatidiform mole.
Biparental complete hydatidiform mole (BiCHM) is a rare form of molar pregnancy, frequently associated with familial recurrence, whose mechanism was historically unclear. It is classically diploid with biparental inheritance, but manifests as a complete hydatidiform mole (CHM). Cytogenetic studies suggested a link to maternal mutations in imprinted genes NOD-like receptor family, pyrin domain containing 7 or Kelch helper domain containing 3-like within the oocyte. This case reports a novel gene association. A 43-year-old woman presented with a history of recurrent abnormal pregnancies: 2 CHM and 1 spontaneous abortion following an intracytoplasmic sperm injection (ICSI)-assisted conception. Short tandem repeat polymorphism analysis of products of conception (including both CHM and the aborted ICSI pregnancy) revealed all 3 were biparental triploids derived from the patient and her husband. Whole-exome sequencing of the patient's family identified that the patient carries compound heterozygous mutations (c.-82G > A [paternally inherited] and c.*106G > A [maternally inherited]) in the autosomal recessive gene thyroid hormone receptor interactor 13 (TRIP13), confirmed by Sanger sequencing. Given the genetic findings and history of recurrent BiCHM, ovarian donation or adoption was recommended as the treatment strategy to achieve a normal pregnancy. The genetic diagnosis was established, informing future reproductive counseling and management options. To our knowledge, this is the first report linking biallelic TRIP13 mutations to recurrent BiCHM, indicating its potential role in the pathogenesis. ICSI-assisted reproduction did not improve pregnancy outcomes. Ovarian donation or adoption was recommended.
2025-06-15 | GTN misdiagnosed as ectopic pregnancy: a 17-year retrospective cohort study.
To evaluate the effect of misdiagnosis on the chemotherapy response and prognosis of gestational trophoblastic neoplasia (GTN), and to explore strategies to enhance precision management of uncertain GTN. GTN patients misdiagnosed as ectopic pregnancies were retrospectively enrolled. GTN without misdiagnosis were randomly selected as control group at a 1:1 ratio, matching by age, WHO risk score and admission year. All patients were followed up for pregnancy, recurrence, and survival. Mann-Whitney test was used for continuous variables. Categorical variables were assessed using the Chi-square test or Fisher's exact test. Among 35 misdiagnosed cases, high-risk GTN accounted for 57.1 %. Antecedent nonmolar pregnancy in misdiagnosed group was 88.6 %. Pretreatment human chorionic gonadotropin (hCG) was lower (3477 vs 18,121 IU/L) while recurrence rate was significantly higher in misdiagnosed group than in control group (28.6 % vs 5.7 %, p = 0.011). The resistance rate showed an increasing trend in misdiagnosed group (22.9 % vs 14.3 %, p = 0.356). For subgroup analysis, the resistance rate was increased in group A (treated with methotrexate) than group B (without methotrexate), while decreased in patients with lesion resection (group C) than without resection (group D), especially for low-risk patients. Histopathological misdiagnosis for antecedent pregnancy and GTN in primary hospitals were 2 and 6 cases respectively. GTN after nonmolar pregnancy with low hCG are prone to be misdiagnosed, which might lead to increased WHO risk scores, resistance, and relapse rates. Surgical intervention, especially lesion resection instead of methotrexate, is recommended for atypical GTN.
2025-05-05 | Is gestational trophoblastic neoplasia more common among women with recurrent hydatidiform moles and biallelic NLRP7 mutations? a 17-years prospective study from India.
Recurrent hydatidiform moles (RHM) is a rare entity defined by the occurrence of two or more hydatidiform moles (HM) in a woman. We present data of women with RHM from a tertiary care institute in North India with respect to the incidence of Gestational Trophoblastic Neoplasia (GTN), subsequent reproductive outcome and genetic analysis in this cohort. Women who presented with RHM and no prior live birth were enrolled from 2005 to 2022 and analysed for the presence of pathogenic or likely pathogenic (P/LP) variants in genes responsible for RHM. They were followed-up for occurrence of post-molar GTN as per FIGO and WHO guidelines, and subsequent reproductive outcomes. Of the 23 women with RHM, 22 (95.6 %) had biallelic P/LP variants in three genes, 20 in NLRP7 (87 %), one in KHDC3L (4 %), and one in TOP6BL (4 %). Of the 20 women with NLRP7 variants, 10 (50 %) developed GTN, mostly low-risk, which is approximately 2 to 3 times higher than the rate of GTN among women with sporadic HM at similar ages. Three of these women had recurrent GTN. Among the 22 women with biallelic P/LP variants, only one had a spontaneous live birth, and four underwent IVF with donated ova, of whom three had live births. Only one woman was negative for recessive causative variants in the known genes or any novel gene and she subsequently had two spontaneous live births. Our data indicate a high incidence of biallelic P/LP NLRP7 variants among Indian women with RHM and no live birth. These women appeared to be at a higher risk for developing GTN and had a very low chance of a spontaneous live birth, and these two concerns may be mitigated by avoiding a spontaneous pregnancy and having donor ovum IVF. All women with RHM should have genetic testing and counseling specifically due to their higher risk of GTN.
2024-10-11 | The role of extracellular vesicles in the pathogenesis of gynecological cancer.
Gynecological cancer, the most common form of cancers in women worldwide, initiates in the reproductive organs of females. More often, the common treatment measures, i.e. surgery, radiation, and medical oncology are found to be unsuccessful in the treatment of gynecological tumors. Emerging evidence indicates that extracellular vesicles (EVs) play a significant role in the pathogenesis of gynecological cancers by distinct mechanisms. The present review highlights how EVs contribute to the progression of different types of gynecological cancers such as cervical cancer, endometrial cancer, ovarian cancer, vaginal cancer, uterine sarcoma, gestational trophoblastic disease (GTD), and vulvar cancer. The primary focus is to understand how EVs' cargo alters the phenotypic response of the recipient cells, thereby contributing to the progression of the disease, thus can be considered as a prognostic and diagnostic biomarker. A brief discussion on the role of EVs in the diagnosis and prognosis of different gynecological cancer types is also highlighted. Targeting the biogenesis of the EVs, their inside cargo, and EVs uptake by the recipient cells could be a potential therapeutic approach in the treatment of gynecological cancer beside conventional therapeutic means.
2024-06-04 | Surgical Management of Gestational Trophoblastic Disease.
Gestational trophoblastic disease (GTD) is a rare pregnancy-related condition consisting of premalignant and malignant forms arising from proliferation of trophoblastic cells. The malignant forms are collectively referred to as gestational trophoblastic neoplasia (GTN) and are highly sensitive to chemotherapy. However, surgical procedures remain indispensable in the diagnosis and treatment of GTD. The aim of this review was to summarize surgical interventions in the treatment of GTD and GTN. We reviewed indications, efficacy, possible complications, and oncological outcomes of surgery. Three searches were performed in the databases of PubMed, Embase, and the Cochrane Library to create an up-to-date overview of existing literature on the following subjects: (1) the role of primary hysterectomy in GTD and GTN; (2) the role of second curettage in GTD and GTN; (3) fertility sparing surgery in GTN; (4) surgical management of metastases. Included articles originated from the time period 1952-2022. Articles written in English, Spanish, and French were included. Thirty-eight articles were found and selected. Surgical evacuation through suction curettage is most used and advised in the treatment of GTD. A second curettage could be beneficial in patients with low hCG levels and low FIGO scores. In women who have completed their families, primary hysterectomy might be considered as the risk of subsequent GTN is lower than after suction curettage. In case of the rare forms of GTN (epithelioid trophoblastic tumor or placental site trophoblastic tumor) surgical tumor resection remains the most important step in treatment. Data on fertility sparing surgery in GTN are scarce and this treatment should be considered experimental. Surgery remains an important part of treatment of GTD and is sometimes indispensable to achieve curation. Further collection of evidence is needed to determine treatment steps.
antibodies
2026-07-30 | Gestational Trophoblastic Diseases. An Overview of Patients visiting Sheikh Zayed Medical Hospital, Rahim Yar Khan
Background: Gestational trophoblastic disease is an important obstetric condition which if untreated, can result in serious and harmful consequences. Objective of this study was to determine incidence and pattern of gestational trophoblastic disease in tertiary care hospital of Rahim Yar khan. Methods: This prospective observational cohort study was conducted at Sheikh Zayed Medical Hospital, Rahim Yar Khan, from January 2019 to December 2022. Patients presented with gestational amenorrhea and vaginal bleeding were sus-pected to be cases of molar pregnancy based on certain distinct clinical factors. These indicators included a large-for-date symphysio-fundal height (SFH), a snow storm appearance on ultrasonography, and significantly higher serum β-hCG levels. Data for these specific cases was collected from molar pregnancy registers maintained in Obstetrics and Gynecology de-partment of Sheikh Zayed Medical Hospital, Rahim Yar Khan. Final diagnosis of molar pregnancy was confirmed by histo-pathology of the tissue removed from uterine cavity by suction and evacuation. Results: A total of 33,494 pregnant women were admitted during the study period. Among this population, 197 were diag-nosed with a molar pregnancy, representing a 0.58% rate. This equates to an overall incidence of 5.8 per 1,000 obstetric admission. Complete hydatidiform mole was the most common type, diagnosed in 127 females (64.4%). Partial mole oc-curred in 58 females (29.4%), while choriocarcinoma was found in 12 females (6.1%). Among 12 women with choriocarci-noma, four presented with pulmonary metastasis, received multiagent chemotherapy in liaison with oncology department.Conclusion: High sensitivity pelvic ultrasonography may have led to early detection of abnormal pregnancies, before we can detect classical symptoms or identify patients with advanced disease.
2026-07-20 | Gynecologic Cancer—A Global Platform for Inclusive Collaboration and Excellence in Gynecologic Oncology
Gynecologic Cancers—including ovarian, fallopian tube, endometrial, cervical, vulvar, as well as placental and gestational trophoblastic diseases—remain a major global health burden despite decades of scientific progress [...]
2026-06-26 | A Case of Placental Site Trophoblastic Tumour That Mimicked Missed Miscarriage.
Background and Clinical Significance: Placental site trophoblastic tumour (PSTT) is a malignant tumour of the implantation site intermediate trophoblasts. It has historically been described using terms such as atypical chorioepithelioma, atypical choriocarcinoma, syncytioma, and chorioepitheliosis. It belongs to one of the heterogeneous spectrums of gestational trophoblastic disease. It accounts for about 0.25 to 5% of all gestational trophoblastic neoplasia. The typical clinical presentation is alternating menorrhagia and amenorrhea, mildly elevated β-hCG, and radiological findings of a uterine mass. Case Presentation: A 32-year-old woman presented with a history of intermittent menorrhagia and amenorrhea, with a persistent mildly raised β-hCG level. Ultrasonography showed a hypoechoic lesion on the right side of the posterior wall of the uterus. She was diagnosed with a missed miscarriage, and an evacuation of the products of conception was performed. Histologically, the tissue fragments comprised cords and sheets of atypical intermediate trophoblast cells, with characteristic features of myometrial smooth muscle infiltration, vascular invasion, and vascular wall replaced by the neoplastic cells. Immunohistochemically, these cells are positive for β-hCG and GATA3, while negative for P63. Conclusions: PSTT is a rare form of gestational trophoblastic neoplasia. Early recognition of PSTT is essential because its clinical presentation may mimic benign pregnancy-related conditions, and diagnosis relies heavily on histopathological and immunohistochemical evaluation.
2026-06-22 | Refractory ultra-high-risk Choriocarcinoma achieving complete response to intensive multi-agent and intrathecal chemotherapy and anti-PD-L1 therapy.
Background: Choriocarcinoma is a highly aggressive gestational trophoblastic neoplasm. Patients with ultra-high-risk disease (FIGO score ≥ 13) and brain metastases face cure rates of only 50-80% and require intensive multimodal therapy. Case: We present the case of a 37-year-old woman with stage IV choriocarcinoma (FIGO score 14 ultra-high-risk) who presented with lung and brain metastases. Despite an initial response to standard chemotherapy, she experienced early relapse with progressive central nervous system disease. She received salvage treatment with intensive multi-agent escalated EP chemotherapy, intrathecal methotrexate, and pembrolizumab (anti-PD-1) introduced at cycle three and stereotactic radiosurgery for residual CNS disease, achieving a complete radiological and biochemical response sustained for over one year. Conclusion: This case highlights the challenges of managing ultra-high-risk gestational trophoblastic neoplasia and underscores the importance of multidisciplinary collaboration. The complete response achieved with the addition of pembrolizumab to dose-intensified, intrathecal, and high-dose chemotherapy supports the use of immune checkpoint inhibition in the management of refractory ultra-high-risk GTN.
2026-05-15 | A Rare Case of Primary Pulmonary Choriocarcinoma Metastasizing to the Kidney: Diagnostic and Therapeutic Complexities.
Choriocarcinoma is a highly aggressive malignant tumor composed primarily of cytotrophoblast and syncytiotrophoblast cells without villi and is characterized by beta-human chorionic (beta-hCG) gonadotropin production. Although most cases are of gestational origin, rare non-gestational choriocarcinomas may arise from pluripotent germ cells in extragenital locations, independently of pregnancy. Primary pulmonary choriocarcinoma is extremely rare, and kidney metastasis has only exceptionally been reported in the literature. We present the case of a 43-year-old patient with this unusual presentation. The diagnostic process began with a suspected implantation of unknown location and culminated in the final histopathological diagnosis based on lobectomy and nephrectomy specimens, including molecular genetic identification of the pulmonary tumor. Following thoracic and renal surgery, the patient received adjuvant chemotherapy and immunotherapy with anti-PD-1 monoclonal antibodies. This case highlighted the diagnostic challenges posed by primary pulmonary choriocarcinoma with renal metastasis, an exceptionally rare clinical entity. Ongoing follow-up includes regular imaging studies and beta-hCG monitoring.
oligonucleotides
2024-02-19 | Twist-1 Stimulates the Malignant Behaviors of Hydatidiform Mole via the PI3K/AKT Pathway
Background: Hydatidiform mole (HM) is a common pregnancy disease among women of gestational age. Twist-related protein 1 (Twist-1) is involved in the development of various tumors, but its role in HM is poorly defined. This study aimed to explore Twist-1 expression and its biological function in HM cells. Methods: Twist-1 expression in HM was detected by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). The effects of silencing Twist-1 on choriocarcinoma (CCA) cell proliferation were detected by cell counting kit-8 (CCK-8) and clone formation assays. CCA cell migration and invasion were detected through transwell assay. Western blot was used to detect epithelial–mesenchymal transition (EMT) and the expression of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway-related proteins. Results: Twist-1 expression was upregulated in HM tissues (p < 0.001) and CCA cells (p < 0.01). Twist-1 silencing inhibited proliferation of BeWo and JAR cells (p < 0.01, p < 0.05) as shown by CCK-8 assay (p < 0.01) and clone formation assays (p < 0.01, p < 0.05). Twist-1 silencing inhibited the migration (p < 0.01) and invasion activity (p < 0.01, p < 0.05) of BeWo and JAR cells. Western blot results showed that Twist-1 silencing promoted E-cadherin (p < 0.01) expression, and inhibited N-cadherin (p < 0.01, p < 0.05) and vimentin (p < 0.01, p < 0.05) expression in BeWo and JAR cells. Twist-1 downregulation decreased protein levels of p-PI3K (p < 0.01) and p-AKT (p < 0.01, p < 0.05) in BeWo and JAR cells. Conclusions: Silencing Twist-1 inhibits the malignant behavior of CCA cells, which may play a part by inhibiting the EMT process and the PI3K/AKT pathway.
2022-10-18 | METTL3 m6A-dependently promotes miR-21-5p maturation to accelerate choriocarcinoma progression via the HIF1AN-induced inactivation of the HIF1A/VEGF pathway.
Gestational choriocarcinoma is a highly malignant neoplastic disease derived from pathological changes in trophoblastic cells. Recent evidences have shown that N6-methyladenosine (m6A) modifications play important role in modulating the development of multiple cancers, but the detailed mechanisms by which m6A-mediated choriocarcinoma progression have not been fully delineated. This study aimed to investigate the role of m6A in choriocarcinoma and reveal its underlying molecular mechanisms. The expression of METTL3, miR-21-5p and HIF1AN was detected using RT-qPCR in tissues and cells. The protein expression of METTL3, HIF1AN, HIF1A and VEGF were measured by western blot. The luciferase reporter assays and RNA immunoprecipitation (RIP) were used to verify the relationship between miR-21-5p and HIF1AN. The CCK-8, colony formation and transwell assays were used to detected cell proliferation and cell migration, respectively. Here, we demonstrated that the m6A methyltransferase-like 3 (METTL3) was aberrantly high-expressed in the clinical choriocarcinoma tissues and choriocarcinoma cell lines compared to the corresponding normal counterparts. The following functional experiments verified that silencing of METTL3 suppressed cell proliferation, migration, epithelial-mesenchymal transition (EMT) and tumorigenesis in vitro and in vivo to hamper the aggressiveness of choriocarcinoma. Next, the mechanical experiments confirmed that METTL3 promoted the maturation of miR-21-5p in an m6A-dependent manner, and elevated miR-21-5p subsequently degraded its downstream hypoxia-inducible factor asparagine hydroxylase (HIF1AN) by targeting its 3' untranslated regions (3'-UTR), resulting in the activation of the tumor-promoting HIF1A/VEGF pathway. Finally, the rescuing experiments verified that METTL3 ablation-induced inhibitory effects on the malignant phenotypes in choriocarcinoma were all abrogated by both miR-21-5p overexpression and HIF1AN downregulation. Collectively, this study firstly reported the involvement of the METTL3/m6A/miR-21-5p/HIF1AN signaling cascade in regulating the progression of choriocarcinoma, which provided novel biomarkers for the diagnosis and treatment of this disease.
2022-06-06 | CBR3-AS1 Accelerates the Malignant Proliferation of Gestational Choriocarcinoma Cells by Stabilizing SETD4.
Gestational choriocarcinoma (GC) is a rare malignant gestational trophoblastic tumor. Long noncoding RNA (lncRNA) CBR3 antisense RNA 1 (CBR3-AS1) has been reported to serve as a critical oncogene and facilitate tumor progression. Besides, we found that CBR3-AS1 is implicated in GC progression. Gene and protein expression was detected via quantitative reverse transcription PCR (RT-qPCR) and western blot analyses, respectively. CCK-8 assay and colony formation assay were performed to assess cell proliferative abilities while flow cytometry analysis was applied for cell cycle and apoptosis. To analyze the specific mechanism among CBR3-AS1, SET domain containing 4 (SETD4), and polypyrimidine tract binding protein 1 (PTBP1), RNA binding protein immunoprecipitation (RIP), RNA pulldown, and mRNA stability assays were conducted. CBR3-AS1 was markedly upregulated in GC cells, and its downregulation suppressed cell proliferation, induced cell cycle arrest, but promoted cell apoptosis in GC. SETD4 was determined as the downstream mRNA of CBR3-AS1 and positively regulated by CBR3-AS1 in GC cells. Furthermore, CBR3-AS1 could interact with its RNA binding protein (RBP) PTBP1, thereby stabilizing SETD4 mRNA. Rescue assays verified that CBR3-AS1 facilitates GC cell malignant proliferation via SETD4. CBR3-AS1 accelerates the malignant proliferation of GC cells via stabilizing SETD4.
2022-03-04 | Prediction of Neoplastic Transformation of Hydatidiform Mole: Current Evidence.
Gestational trophoblastic disease is not an uncommonly encountered pathology in clinical practice. The rate of post-molar neoplastic transformation is around 5-20% with higher rates after complete versus partial molar pregnancies. Recently, a role for molecular and genetic markers in the prediction of neoplastic transformation has emerged. We read with interest the article by St. Laurent et al. published in this issue of Reproductive Sciences. The authors compared miRNA profiles between complete hydatidiform moles (CHMs) and pre-gestational trophoblastic neoplasia CHM samples at three distinct tropho-miRNA clusters, 14q32, C19MC, and miR-371-3, as well as the expression of the contiguous DLK1, DIO3, and RTL1 genes. They found significant differences in expression of the 14q32 miRNA cluster and a fivefold decrease in protein expression of DIO3 but no difference in DIO3 mRNA expression. We reviewed the literature for similar studies looking at predictive tools for neoplastic transformation. We encourage future randomized controlled trials using these 2 novel risk predictors postulated by St. Laurent et al. to validate and guide future prophylactic chemotherapy for prevention of post-molar GTN.
2022-03-04 | miR-30a targets STOX2 to increase cell proliferation and metastasis in hydatidiform moles via ERK, AKT, and P38 signaling pathways
Abstract Background A hydatidiform mole is a condition caused by abnormal proliferation of trophoblastic cells. MicroRNA miR-30a acts as a tumor suppressor gene in most tumors and participates in the development of various cancers. However, its role in hydatidiform moles is not clear. Methods Quantitative real-time reverse transcription PCR was used to verify the expression level of miR-30a and STOX2 (encoding storkhead box 2). Flow cytometry assays were performed to detect the cell cycle in cell with different expression levels of miR-30a and STOX2 . Cell Cycle Kit-8, 5-ethynyl-2′-deoxyuridine, and colony formation assays were used to detect cell proliferation and viability. Transwell assays was used to test cell invasion and migration. Dual-luciferase reporter assays and western blotting were used to investigate the potential mechanisms involved. Result Low miR-30a expression promoted the proliferation, migration, and invasion of trophoblastic cells (JAR and HTR-8). Dual luciferase assays confirmed that STOX2 is a target of miR-30a and resisted the effect of upregulated miR-30a in trophoblastic cells. In addition, downregulation of STOX2 by miR-30a could activate ERK, AKT, and P38 signaling pathways. These results revealed a new mechanism by which ERK, AKT, and P38 activation by miR-30a/STOX2 results in excessive proliferation of trophoblast cells in the hydatidiform mole. Conclusions In this study, we found that miR-30a plays an important role in the development of the hydatidiform mole. Our findings indicate that miR-30a might promote the malignant transformation of human trophoblastic cells by regulating STOX2 , which strengthens our understanding of the role of miR-30a in regulating trophoblastic cell transformation.
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2024-05-02 | Organ-preserving treatment of a patient with a trophoblastic tumor of the placental bed (clinical observation and literature review)
Placental site trophoblastic tumor (PSTT) is а rare form of gestational trophoblastic neoplasia (GTN), accounting 0,2 % of total cases of GTN. PSTTs occur in women of childbearing age and most of them have strong desire to preserve fertility. PSSTs are tumors with unpredictable biological behavior, high chemo-resistance and possibly fatal outcome in case of metastatic disease. Hysterectomy is the primary treatment of choice in early disease. We report a rare clinical case of fertility sparing treatment for PSTT.
2024-01-25 | Oncostatin M and STAT3 Signaling Pathways Support Human Trophoblast Differentiation by Inhibiting Inflammatory Stress in Response to IFNγ and GM-CSF
Interleukin-6 (IL-6) superfamily cytokines play critical roles during human pregnancy by promoting trophoblast differentiation, invasion, and endocrine function, and maintaining embryo immunotolerance and protection. In contrast, the unbalanced activity of pro-inflammatory factors such as interferon gamma (IFNγ) and granulocyte–macrophage colony-stimulating factor (GM-CSF) at the maternal–fetal interface have detrimental effects on trophoblast function and differentiation. This study demonstrates how the IL-6 cytokine family member oncostatin M (OSM) and STAT3 activation regulate trophoblast fusion and endocrine function in response to pro-inflammatory stress induced by IFNγ and GM-CSF. Using human cytotrophoblast-like BeWo (CT/BW) cells, differentiated in villous syncytiotrophoblast (VST/BW) cells, we show that beta-human chorionic gonadotrophin (βhCG) production and cell fusion process are affected in response to IFNγ or GM-CSF. However, those effects are abrogated with OSM by modulating the activation of IFNγ-STAT1 and GM-CSF-STAT5 signaling pathways. OSM stimulation enhances the expression of STAT3, the phosphorylation of STAT3 and SMAD2, and the induction of negative regulators of inflammation (e.g., IL-10 and TGFβ1) and cytokine signaling (e.g., SOCS1 and SOCS3). Using STAT3-deficient VST/BW cells, we show that STAT3 expression is required for OSM to regulate the effects of IFNγ in βhCG and E-cadherin expression. In contrast, OSM retains its modulatory effect on GM-CSF-STAT5 pathway activation even in STAT3-deficient VST/BW cells, suggesting that OSM uses STAT3-dependent and -independent mechanisms to modulate the activation of pro-inflammatory pathways IFNγ-STAT1 and GM-CSF-STAT5. Moreover, STAT3 deficiency in VST/BW cells leads to the production of both a large amount of βhCG and an enhanced expression of activated STAT5 induced by GM-CSF, independently of OSM, suggesting a key role for STAT3 in βhCG production and trophoblast differentiation through STAT5 modulation. In conclusion, our study describes for the first time the critical role played by OSM and STAT3 signaling pathways to preserve and regulate trophoblast biological functions during inflammatory stress.
2024-01-16 | Impact of molecular genotyping on the diagnosis and treatment of human chorionic gonadotropin-producing tumors.
To assess the use of molecular genotyping to accurately diagnose and treat human chorionic gonadotropin (hCG)-producing tumors and to evaluate the discriminating capacity of molecular testing on prognosis and overall survival. We conducted a retrospective descriptive study of patients registered with the French Reference Center for Trophoblastic Disease between 1999 and 2021. We included all patients with hCG-producing tumors for whom results of molecular genotyping were available. Fifty-five patients with molecular genotyping were included: 81.2 % (n = 45) had tumors of gestational origin, 12.7 % (n = 7) of non-gestational origin and 5.5 % (n = 3) of undetermined origin. The results of molecular genotyping influenced the treatment decisions for 17 % of patients in this cohort. Overall survival was 93.3 % for patients with gestational tumors (after a median follow-up of 74 months) compared to 71.4 % for patients with non-gestational tumors (after a median follow-up of 23 months). In atypical presentations of hCG-producing tumors, molecular genotyping is a valuable tool to guide diagnosis and tailor treatment recommendations.
2023-02-15 | Current chemotherapeutic options for the treatment of gestational trophoblastic disease.
Gestational trophoblastic neoplasia (GTN) is a rare tumor that arises from trophoblastic tissues with high remission rates after chemotherapy treatment. GTN can develop from any gestational events, such as miscarriage, ectopic pregnancy, and preterm/term pregnancy, but is more frequent after hydatidiform mole. The sensitivity of this tumor to chemotherapy and the presence of an exceptional tumor marker allow high remission rates, especially when patients are treated in referral centers. Observational, retrospective, prospective, systematic reviews, and meta-analysis studies focusing on GTN treatment. We searched PubMed, Medline, and the Library of Congress from January 1965 to May 2022. Early GTN diagnosis allows low-toxic and highly effective treatment. Even multimetastatic disease has high rates of remission with multiagent regimen chemotherapy. Surgery is reserved for uterine disease in patients who have completed childbearing, in cases of chemoresistance to multiagent regimens or in the rare cases of placental site trophoblastic tumor or epithelioid trophoblastic tumor. While resistance is managed by salvage chemotherapy, cases with limited clinical response to sequential regimens have been successfully treated with immunotherapy.
2022-05-09 | The immune microenvironment of the hydatidiform mole.
Gestational trophoblastic diseases (GTDs) are a heterogeneous group of lesions, the most frequent being the hydatidiform mole (HM). HMs are usually cured after surgical treatment or after chemotherapy in the case of a persistent trophoblastic activity. Immunotherapy could be an interesting alternative as a first-line or second-line treatment. However, only a few studies have explored the immune microenvironment of HMs. In the present retrospective study including 19 complete and 17 partial moles, we examined the composition of the immune cell microenvironment by immunohistochemistry using the following antibodies: CD4, CD8, CD56, PD-L1, S100, CD83, CD207, CD123, CD1a, CD11c, CD163, PAX5, and MUM1. In the decidual cells compartment, CD11c+ cells were the predominant population, followed by CD4+ cells, CD56+ NK cells, CD163+ macrophages, and CD8+ T lymphocytes.In the endometrial glands compartment, CD11c+ cells were the predominant population, followed by CD4+ cells, CD56+ NK cells, and CD8+ T lymphocytes. In the villi compartment, the predominant immune cells were CD4+ cells, followed by CD163+ macrophages and CD11c+ cells. Statistically significant differences were observed between partial and complete moles in all three compartments. The immune microenvironment of HMs is immunosuppressive, but it differs between complete and partial moles, the latter having a higher infiltrate of cells with phenotypes suggestive of immunosuppressive activities.
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