Malignant Trophoblastic Tumor Research Articles

Subcutaneous choriocarcinomas in captive Amargosa voles (Microtus californicus scirpensis).

Spontaneous choriocarcinomas are rare, highly vascular, malignant trophoblastic tumors that occur in humans and animals. This report describes the unusual spontaneous presentation of 4 choriocarcinomas within the subcutaneous tissues of 4, multiparous but nongravid, Amargosa voles (Microtus californicus scirpensis) from a captive breeding colony. Two subcutaneous neoplasms were composed of multifocal discohesive and infiltrative aggregates of medium to large trophoblasts and cytotrophoblasts within a fibrovascular stroma. Neoplastic cells were associated with variably sized thrombi and cavitary areas of hemorrhage and necrosis. Two subcutaneous tumors were predominantly composed of expansile, blood-filled, cystic spaces lined by neoplastic cytotrophoblasts and occasionally contained medium to large trophoblasts. Trophoblasts and cytotrophoblasts were positive for pancytokeratin and cytokeratin 8/18, negative for alpha-fetoprotein, and contained intracytoplasmic Periodic acid-Schiff (PAS)-positive glycogen in all 4 tumors. In species with hemochorial placentation, migration of trophoblasts into maternal circulation with embolization to distant nonreproductive tissues occurs and may explain the unusual subcutaneous distribution of these 4 tumors. The 2 multiloculated paucicellular tumors may represent an early stage of neoplastic transformation. To the authors' knowledge, this is the first report characterizing choriocarcinomas in extrareproductive sites in rodents.

All-Trans Retinoic Acid Reduces Matrix Metalloproteinase-2 and Increases E-Cadherin Levels in BeWo Choriocarcinoma Cells

Background: Choriocarcinoma is a malignant trophoblastic tumor that can degrade the uterine basement membrane to facilitate local and distant metastasis. Matrix metalloproteinase-2 (MMP-2) is a vital proteinase produced by trophoblasts and can cleave type IV collagen in the basement membrane of the uterine epithelium. In addition, E-cadherin controls cell adhesion, which is associated with tumorprogression, and loss of E-cadherin function is associated with metastasis. Vitamin A analogues, including all-trans retinoic acid (ATRA), exhibit anticancer properties, including metastasis inhibition.This study aimed to investigate the ability of ATRA to prevent trophoblast invasion and metastasis in choriocarcinoma by assessing MMP-2 and E-cadherin activity. Methods: This study administered various doses of ATRA to the BeWo (American Type Culture Collection CCL-98) choriocarcinoma cell line and assessed MMP-2 and E-cadherin activity through flow cytometry. The research was performed at the Biomedical Laboratory of the Faculty of Medicine of Universitas Brawijaya Malang, East Java, Indonesia. Results: BeWo cells were exposed to 0, 50, 100, 200, 400, or 800 μg/mL ATRA. MMP-2 was downregulated after ATRA treatment. The greatest reduction in MMP-2 level was observed after 200 μg/mL ATRA treatment, but this result was not statistically significant (P = 0.550). However, ATRA treatment significantly reduced the number of BeWo cells with low E-cadherin levels (P = 0.012). Conclusion: ATRA downregulates MMP-2 and upregulates E-cadherin. Further in vitro and animal studies are required to evaluate the ability of ATRA to inhibit metastasis. Bangladesh Journal of Medical Science Vol. 22 No. 02 April’23 Page : 336-340

NLRP7 Enhances Choriocarcinoma Cell Survival and Camouflage in an Inflammasome Independent Pathway.

Gestational choriocarcinoma (GC) is a highly malignant trophoblastic tumor that often develops from a complete hydatidiform mole (HM). NLRP7 is the major gene responsible for recurrent HM and is involved in the innate immune response, inflammation and apoptosis. NLRP7 can function in an inflammasome-dependent or -independent pathway. Recently, we have demonstrated that NLRP7 is highly expressed in GC tumor cells and contributes to their tumorigenesis. However, the underlying mechanisms are still unknown. Here, we investigated the mechanism by which NLRP7 controls these processes in malignant (JEG-3) and non-tumor (HTR8/SVneo) trophoblastic cells. Cell survival, dedifferentiation, camouflage, and aggressiveness were compared between normal JEG-3 cells or knockdown for NLRP7, JEG-3 Sh NLRP7. In addition, HTR8/SVneo cells overexpressing NLRP7 were used to determine the impact of NLRP7 overexpression on non-tumor cells. NLRP7 involvement in tumor cell growth and tolerance was further characterized in vivo using the metastatic mouse model of GC. We demonstrate that NLRP7 (i) functions in an inflammasome-dependent and -independent manners in HTR8/SVneo and JEG-3 cells, respectively; (ii) differentially regulates the activity of NF-κB in tumor and non-tumor cells; (iii) increases malignant cell survival, dedifferentiation, and camouflage; and (iv) facilitates tumor cells colonization of the lungs in the preclinical model of GC. This study demonstrates for the first time the mechanism by which NLRP7, independently of its inflammasome machinery, contributes to GC growth and tumorigenesis. The clinical relevance of NLRP7 in this rare cancer highlights its potential therapeutic promise as a molecular target to treat resistant GC patients.

Splenic Metastatic Choriocarcinoma with Nontraumatic Splenic Rupture: A Case Report and Literature Review

Choriocarcinoma is a highly malignant trophoblastic tumor that occurs mostly in women of childbearing age. The main mode of metastasis is hematogenous metastasis. The most common sites of metastasis are the lung, vagina and brain, while splenic metastasis is rare. Because of its rapid development, extensive metastasis can occur in a short period, and some patients only show metastatic symptoms, which are often missed or misdiagnosed as ectopic pregnancy or other diseases. We describe a rare case of splenic metastatic choriocarcinoma with acute abdominal pain caused by nontraumatic splenic rupture. In addition, we review the previous literature on splenic metastasis of choriocarcinoma and summarize the clinical manifestations, management measures and prognoses. Our case and literature review indicate that splenic metastatic choriocarcinoma is rare and difficult to distinguish from splenic ectopic pregnancy and other diseases. Clinicians should strengthen their understanding of this disease and avoid misdiagnosis.

Analysis of the Outcome of Treatment of Brain Metastases from Malignant Trophoblastic Tumours and Risk Factors for Prognosis during Pregnancy.

Temozolomide combined with whole-brain radiotherapy has good near-term efficacy and safety in the treatment of brain metastases from nonsmall cell lung cancer. In this study, we analyzed the risk factors for treatment and prognosis of brain metastases in gestational trophoblastic neoplasm (GTN) during pregnancy. Thirty-one patients with brain metastases were included in the study. All patients had a pathological diagnosis of primary lesions, including 23 adenocarcinomas, 7 squamous carcinomas, and 1 adenosquamous carcinoma, and had ≥3 intracranial metastases, controlled primary lesions (including resected primary lesions or unresectable primary lesions in partial remission (PR)/complete remission (CR) for ≥2 months) by cranial enhancement MRI and no extracranial metastases. Presence or control of extracranial metastases was for ≥2 months. The common adverse toxic effects were nausea, vomiting, neutropenia, and thrombocytopenia, but most patients tolerated them with symptomatic management.

Clinicopathological analysis of lung metastatic tumor

Objective: To investigate the clinicopathological features and differential diagnosis of metastatic tumors in the lung. Methods: The clinicopathological data of 226 metastatic tumors in the lung were collected at Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, from January 2014 to December 2018, and the pathomorphological characteristics were analyzed. Results: There were 84 males and 142 females, with an age range from 13 to 77 years. There were 122 patients with multiple pulmonary nodules and 104 patients with solitary pulmonary nodule. The tumors of the highest frequencies were colorectal cancer (n=59), followed by trophoblast tumor (n=44), kidney cancer (n=31), breast cancer (n=20), cervix cancer (n=14), and urinary urothelium cancer (n=8). The time from the diagnosis of primary tumors to metastasis and the status of surgical treatment varied by tumor origin. The morphology of metastatic lung tumors overlapped with that of the primary tumors to some extent. The relative specific morphological characteristics and the presence of carcinoma in situ surrounding the tumors should be carefully searched for to confirm the tumor origin. The metastatic tumors of the lung had morphological characteristics, immunohistochemical TTF1 (-) and tumor of various sources, while the primary tumor differentiation had relatively specific antibodies: colorectal cancer CK20 (+), CDX2 (+), CK7 (-); malignant trophoblastic tumor, HCG (+); renal clear cell carcinoma CD10 (+), vimentin (+), CK7 (-); breast cancer, GATA3 and ER (+); cervical cancer, p16 (+); urothelial carcinoma, CK20, p63 and GATA3 (+). Conclusions: There is overlap between pulmonary metastatic tumor and primary tumor in morphology. Therefore, the diagnosis should be made by combining clinical history, pathological morphology and immunophenotypic characteristics.

Modern approaches to the diagnosis of malignant trophoblastic tumors

Malignant trophoblastic tumors (TO) include invasive and metastatic cystic drift, choriocarcinoma, TO of the placental bed, and epithelioid TO. They are rare, mainly in women of reproductive age, and most importantly, they are always associated with pregnancy. To date, the Blokhin National Medical Research Center of Oncology has accumulated a large and unique experience of modern diagnostics and treatment of patients with various forms of malignant TO. An obligatory stage of the examination is ultrasound diagnostics of the pelvic organs. In addition, performing an ultrasound examination during the treatment period, along with monitoring the level of chorionic gonadotropin, makes it possible to assess the effectiveness of treatment, diagnose tumor resistance and ascertain the onset of remission.

Genistein inhibits the proliferation of human choriocarcinoma cells via the downregulation of estrogen receptor-α phosphorylation at serine 118

<h2>Summary</h2><h3>Background & aims</h3> Choriocarcinoma is a malignant trophoblastic tumor. The phosphorylation of estrogen receptor-α at serine 118 (p-ER-s118) decreases cancer cell proliferation. However, the effect of genistein as a modulator of p-ER-s118 and proliferation of chorioarcinoma cells remains to be understood. This study aims at determining the function of genistein on p-ER-s118 levels and human choriocarcinoma JEG-3 cell proliferation. <h3>Methods</h3> After reaching confluency, cells were divided into six groups, the control group (without methyl-piperidino-pyrazole (MPP) pre-treatment and genistein treatment); and groups with cells treated with genistein at concentrations of 0, 10, 25, 50, and 100 μM (cells were pretreated with MPP). Expression of p-ER-s118 and Ki-67 were analyzed using immunocytochemistry. <h3>Results</h3> Different doses of genistein decreased p-ER-s118 levels compared to those in the control (<i>p</i> < 0.05). JEG-3 cell proliferation was inhibited by MPP pre-treatment, concomitant with genistein treatment with a dose of 0 μM, 25 μM, 50 μM, and 100 μM compared to the proliferation of the control cells (<i>p</i> < 0.05). <h3>Conclusion</h3> Taken together, treatment with methyl-piperidino-pyrazole downregulated p-ER-s118. The addition of genistein further decreased the levels of p-ER-s118 and inhibited cell proliferation. Thus, <i>in vivo</i> studies nedd to follow this <i>in vitro</i> study to elucidate the mechanism(s) employed by genistein as an alternative therapy for choriocarcinoma.

Human Chorionic Gonadotropin Polypeptide Nanoparticle Drug Delivery System Improves Methotrexate Efficacy in Gestational Trophoblastic Neoplasia in vitro.

PurposeTo alleviate the sufferings of the chemotherapy patients, we developed a novel active targeted therapeutic system and showed its potential as a promising drug delivery strategy.MethodsWe utilized the human chorionic gonadotropin (HCG) ligand-receptor mediation to make an actively targeted drug delivery system with optimal HCG polypeptide fragment as target head base, polyethylene glycol–polylactic acid copolymers as nanometer materials to load chemotherapy drug methotrexate (MTX), to highly selectively deliver MTX into choriocarcinoma lesions, and to investigate the efficacy, targeting and tolerability of the complex in vitro experiments.ResultsOur data show that choriocarcinoma cell lines JEG-3 and JAR exhibited high expression levels of HCG receptor, peptide HCGβ81-95 specifically bonded to HCG receptor-positive cells and HCG81-NP efficiently delivered MTX to choriocarcinoma cells. HCG81-NP-MTX inhibited cell proliferation and reduced G0/G1 to S phase transition in JEG-3 and JAR cells.ConclusionWe designed an active targeting therapy system of choriocarcinoma, significantly improved chemotherapy efficacy in vitro, and provided a theoretical basis for the treatment of malignant trophoblastic tumors.

Tubal choriocarcinoma presented as ruptured ectopic pregnancy: a case report and review of the literature

BackgroundTubal choriocarcinoma is an extremely rare but highly malignant trophoblastic tumor, which may be either gestational or non-gestational in origin. Due to atypical clinical manifestations and symptoms similar to ectopic pregnancy, it is easily to be confused with ectopic pregnancy. In addition, inadequate understanding of this rare disease by clinicians often leads to misdiagnosis or missed diagnosis, which in turn results in delayed treatment or even tumor metastasis.Case presentationThis report summarized a case of a woman who was finally diagnosed as tubal choriocarcinoma through the follow-up of serum β hCG levels and histopathological results after undergoing salpingectomy for being misdiagnosed as ectopic pregnancy. Five courses of adjuvant chemotherapy (5-fluorouracil, actinomycin-D, vinorelbine regime) have been administered to the patient in the prevention of any recurrences. During 1-year follow-up, the patient was asymptomatic and presented no evidence of recurrence.ConclusionsTubal choriocarcinoma is easily to be confused with ectopic pregnancy. By analyzing this case and previous related cases, we aimed to provide references for clinicians in the diagnosis and treatment of tubal choriocarcinoma.

Tumor-suppressive function of methiothepin in human placental choriocarcinoma cells.

Placental choriocarcinoma is a malignant trophoblastic tumor associated with placentation. During placentation, complicated molecular networks are mediated by endocrine and paracrine signals. Serotonin neurotransmitters have been identified in the transmembrane region of human placental choriocarcinoma (HPC) cells as tumor promoters; therefore, their antagonists have anti-cancer properties. Although methiothepin, a serotonin receptor antagonist and FDA-approved psychotropic agent, has shown multi-pharmacological functions in various disease models, its anti-tumorigenic activity and mechanisms underlying its action against HPC are unknown. Therefore, we identified the anti-cancer effects of methiothepin in JEG3 and JAR HPC cells. Methiothepin attenuated mitochondrial function and induced endoplasmic reticular stress, reducing oxidative phosphorylation and causing metabolic shifting in HPC cells. Furthermore, methiothepin showed synergistic pharmacological effects with paclitaxel in HPC cells. Our results highlight the robust tumor-suppressive function of methiothepin in HPC. Our findings provide new insights into the repositioning of methiothepin from a psychotropic agent to novel anti-cancer agents, especially against HPC.

Surgical treatment of trophoblastic disease. Modern concept and contradictions (literature review)

A review of studies on the comparison of the effectiveness of surgical treatment of malignant trophoblastic tumors before the start of standard chemotherapy and in terms of combination treatment is presented. According to Russian and foreign studies, surgical treatment is relevant for patients with primary or metastatic tumor resistance. The article presents the results of treatment of patients after various types of operations. The most common volume of surgery was a hysterectomy. The article also discusses the results of treatment of benign forms of trophoblastic disease. Surgical treatment of a malignant trophoblastic tumor before the start of standard chemotherapy was performed according to vital indications or in connection with a tumor determined by imaging methods. And the analysis carried out in Blokhin National Medical Research Center of Oncology showed expected prognoses for patients who underwent surgical treatment prior to the start of standard chemotherapy regimens. Such patients were admitted to the clinic with a resistant or disseminated form of the tumor. During their treatment, high-dose chemotherapy or additional surgical interventions were required, which significantly worsened the prognosis of the disease. In the opposite case, when removing a localized resistant primary tumor or its metastasis, in the postoperative period, chemotherapy was not carried out in connection with marker remission.

Epithelioid trophoblastic tumor of the uterus: currently available diagnostic methods, determining an effective treatment strategy (case report)

Gestational trophoblastic disease is a group of pathological conditions of the trophoblast, which includes both benign and malignant forms. Epithelioid trophoblastic tumor is one of the rare malignant trophoblastic tumors. The tumor develops from intermediate trophoblastic cells and is characterized by the absence of villi and presence of clusters of atypical mononuclear trophoblastic cells and elements of syncytiotrophoblast, similar to epithelial cells in their appearance. Patients with epithelioid trophoblastic tumors usually have extragenital tumor foci with no pathology detected in the uterus. Pelvic ultrasound is an essential stage of such patients' examination. Conventional ultrasound and Doppler ultrasonography are informative, reliable, easy to use, and non-invasive diagnostic procedures that provide wide opportunities of dynamic evaluation of the disease during the course of anticancer therapy and subsequent follow up. Comprehensive diagnostics enables timely detection of a rare morphological variant of a malignant trophoblastic tumor and ensures right decision on the treatment strategy, which is the key to a favorable outcome with preserved reproductive function.

β-catenin/LIN28B promotes the proliferation of human choriocarcinoma cells via Let-7a repression.

Choriocarcinoma is a rare and malignant trophoblastic tumor. However, the molecular mechanisms by which choriocarcinoma is regulated remain unknown. In the present study, we first elucidated that LIN28B was highly expressed in human choriocarcinoma tissues and choriocarcinoma cell lines. Our data further demonstrated that knockdown of LIN28B by small interfering RNA caused an increase in Let-7a expression in JAR cells. In addition, silencing of LIN28B inhibited IGF2BP1 expression and suppressed cell proliferation capacity, both of which can be markedly restored by Let-7a inhibitor. In contrast, LIN28B over-expression-improved cell proliferation was inhibited by Let-7a mimic. Knockdown of β-catenin resulted in reduced expression of LIN28B and increased expression of Let-7a. Knockdown of β-catenin also caused a decrease in cell proliferation, which can be recovered by re-expression of LIN28B or by Let-7a inhibitor. Collectively, our data indicate that β-catenin/LIN28B/Let-7a pathway may be crucial for the regulation of cell proliferation in human choriocarcinoma cells.

Critical Conditions In Patients With Malignant Trophoblastic Tumor Of High Risk: Root Cause Analysis And Immediate Treatment Outcomes At The Department Of Emergency Resuscitation And Intensive Care Of The Specialized Oncologic Center For The Period 2007-2017

Critical Conditions In Patients With Malignant Trophoblastic Tumor Of High Risk: Root Cause Analysis And Immediate Treatment Outcomes At The Department Of Emergency Resuscitation And Intensive Care Of The Specialized Oncologic Center For The Period 2007-2017

A rare case of choriocarcinoma after a positive pregnancy test in a postmenopausal woman.

Choriocarcinomas are rare malignant trophoblastic tumors. There is a strong need for development of guidelines for therapeutic decision making.

Dihydromyricetin induces apoptosis in a human choriocarcinoma cell line.

Choriocarcinoma is a malignant trophoblastic tumor. The development of novel drugs is required to reduce the toxicity of current multi-agent chemotherapy and to successfully treat chemoresistant cases of the disease. The purpose of the present study was to investigate the effect of dihydromyricetin (DMY) on the human choriocarcinoma cell line, JAr, to identify a novel drug for the treatment of choriocarcinoma. An MTT assay was performed to determine the effects of DMY at different concentrations and for different exposure durations. Flow cytometry and TUNEL assays were performed to detect apoptosis, and western blotting was utilized to investigate the underlying mechanism. The results revealed that DMY significantly inhibited JAr cell viability in a time- and dose-dependent manner. The flow cytometry and TUNEL assays demonstrated that DMY inhibited proliferation by inducing apoptosis. Further analysis by western blotting indicated that the protein expression level of BCL-2 associated X, associated protein increased, while the protein expression levels of BCL-2 and pro-caspase-3 decreased. These findings suggest that DMY induced apoptosis in human choriocarcinoma JAr cells, through a mitochondrially mediated apoptotic pathway.

Diagnosing and treating rare lesions in a low resource setting: lessons from a hybrid epithelioid trophoblastic tumor and choriocarcinoma

To raise awareness of the existence of a rare type of malignant trophoblastic tumor and discuss the diagnostic challenges and management of this lesion in a low resource setting. A 35 -year -old G6P3 woman was referred to our facility on account of persistent vaginal bleeding due to a suspected incomplete miscarriage with a cervical mass. Her serum β-HCG was elevated (36,900 mIU/ml) and examination showed a bleeding cervical mass. An initial histopathological diagnosis of moderately differentiated squamous cell carcinoma was reviewed to epithelioid trophoblastic tumor resulting in an extra-fascial hysterectomy. A final histopathological diagnosis of hybrid Epithelioid Trophoblastic Tumor and Choriocarcinoma (ETT/CC) was made after external review and immunohistochemistry. She received subsequent chemotherapy. Epithelioid trophoblastic tumor and its hybrids are difficult to diagnose. They may be diagnosed as moderately differentiated squamous cell carcinoma especially in low resource settings where cervical squamous cell carcinoma is relatively more common. A high index of suspicion, a serum β HCG test and close collaboration between clinicians and pathologists can help make the diagnosis. None.

FERTILITY-SPARING HYSTEROTOMY IN MALIGNANT TROPHOBLASTIC TUMOURS TREATMENT

The aim is to improve treatment efficacy and life quality of patients with malignant trophoblastic tumours. Fertility-sparing hysterotomy with uterine reconstruction was carried in 16 patients aged of 17 to 32 years: 2 cases due to urgent and 13 – due to planned indications. On the basis of research, the indications for the urgent and planned fertility-sparing hysterotomy with uterine reconstruction in patients with malignant trophoblastic tumours were formulated. No postoperative complications. Steady remission in all cases. Follow up from 1 to 17 years (averaged 9.2 years). 1. Localized uterine resection with uterine reconstruction – the method of choice in malignant trophoblastic tumours surgical treatment; 2. Fertility-sparing hysterotomy with uterine reconstruction is only possible in centers which are experienced in the complex multimodality treatment of gestational trophoblastic neoplasms; 3. Basic requirement of fertility-sparing surgery is beginning adjuvant chemotherapy as soon as possible.

Gestational Trophoblastic Disease - Clinicopathological Study at Tertiary Care Hospital.

Gestational Trophoblastic Disease (GTD) is a term used for a group of pregnancy-related tumours. These consist of various tumours and tumour like lesions characterized by proliferation of trophoblastic tissue. Amongst GTD, hydatidiform moles are the most common form. These lesions sometimes may develop into invasive moles, or, in rare cases, into choriocarcinoma. To study the clinicopathologic characteristics and prevalence of different forms of gestational trophoblastic disease in a tertiary care hospital. The present study was descriptive, observational, analytical type done in Department of Pathology at tertiary care hospital from May 2012 to April 2016. All cases clinically suspected of GTD were included and confirmation was done by histopathological study on H&E stained slides. The cases of GTD were classified according to WHO classification. Detailed histomorphological features and beta human Chorionic Gonadotropin (hCG) levels were correlated. During study period, 18345 deliveries were reported; out of which 77 cases were diagnosed as GTD. Almost 97.40% cases were of hydatidiform moles, 1.30% cases of choriocarcinoma and 1.30% cases of Placental Site Trophoblastic Tumour (PSTT). Among the cases of hydatidiform mole 57.34% were complete mole and 41.33% cases were of partial mole. The common clinical presentation was per vaginal bleeding and amenorrhea. The blood group A was most commonly observed in patient (49.35%). In majority of cases beta hCG levels were between 50,000 to 100000 mIU/ml. The correlation between beta hCG level and GTD were done. Pregnant females clinically presenting with abnormal vaginal bleeding must be evaluated for GTD. Histopathological examination is helpful for confirmatory diagnosis. Follow up of such patients is essential for early detection of malignant trophoblastic tumours.