scholarly journals LINE-1 Methylation Patterns as a Predictor of Postmolar Gestational Trophoblastic Neoplasia

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ruangsak Lertkhachonsuk ◽  
Krissada Paiwattananupant ◽  
Patou Tantbirojn ◽  
Prakasit Rattanatanyong ◽  
Apiwat Mutirangura
Keyword(s):  
Hydatidiform Mole ◽  
First Trimester ◽  
Methylation Pattern ◽  
Gestational Trophoblastic Neoplasia ◽  
Partial Methylation ◽  
Clinical Appearance ◽  
Malignant Trophoblast ◽  
Sensitivity Specificity ◽  
Methylation Patterns ◽  
Hydatidiform Moles

Objective. To study the potential of long interspersed element-1 (LINE-1) methylation change in the prediction of postmolar gestational trophoblastic neoplasia (GTN).Methods. The LINE-1 methylation pattern from first trimester placenta, hydatidiform mole, and malignant trophoblast specimens were compared. Then, hydatidiform mole patients from 11999 to 2010 were classified into the following 2 groups: a remission group and a group that developed postmolar GTN. Specimens were prepared for a methylation study. The methylation levels and percentages of LINE-1 loci were evaluated for their sensitivity, specificity, and accuracy for the prediction of postmolar GTN.Results. First, 12 placentas, 38 moles, and 19 malignant trophoblast specimens were compared. The hydatidiform mole group had the highest LINE-1 methylation level (p= 0.003) and theuCuC of LINE-1 increased in the malignant trophoblast group (p≤ 0.001). One hundred forty-five hydatidiform mole patients were classified as 103 remission and 42 postmolar GTN patients. The %mCuC and %uCmC of LINE-1 showed the lowestpvalue for distinguishing between the two groups (p< 0.001). The combination of the pretreatmentβ-hCG level (≥100,000 mIU/mL) with the %mCuC and %uCmC, sensitivity, specificity, PPV, NPV, and accuracy modified the levels to 60.0%, 92.2%, 77.4%, 83.8%, and 82.3%, respectively.Conclusions. A reduction in the partial methylation of LINE-1 occurs early before the clinical appearance of malignant transformation. The %mCuC and %uCmC of LINE-1s may be promising markers for monitoring hydatidiform moles before progression to GTN.

scholarly journals Paranoid schizophrenia and methamphetamine-induced paranoia are both characterized by a similar LINE-1 partial methylation profile, which is more pronounced in paranoid schizophrenia

2018 ◽  
Author(s):  
Rasmon Kalayasiri ◽  
Korakot Kraijak ◽  
Apiwat Mutirangura ◽  
Michael Maes
Keyword(s):  
Mononuclear Cells ◽  
Restriction Analysis ◽  
Paranoid Schizophrenia ◽  
Strong Association ◽  
Methylation Pattern ◽  
Peripheral Blood Mononuclear ◽  
Immune Disorder ◽  
Global Methylation ◽  
Partial Methylation ◽  
Methylation Patterns

AbstractBackgroundThere is evidence that schizophrenia is a neuro-immune disorder. Genes linked to intragenic LINE-1 methylation show a strong association with immune-associated disorders including psychosis. The aim of this study was to examine LINE-1 methylation patterns in paranoid schizophrenia and methamphetamine-induced paranoia, a model for schizophrenia.MethodsThis study recruited 31 patients with paranoid schizophrenia, 94 with methamphetamine-induced paranoia (MIP) and 163 normal controls. LINE-1 methylation patterns were assayed in peripheral blood mononuclear cells and a combined bisulphite restriction analysis and COBRA were used to estimate global methylation (mC) and LINE-1 CpG dinucleotide methylation patterns, namely 2 methylated (mCmC) and 2 unmethylated (uCuC) CpGs and the partially methylated loci mCuC (5’m with 3’u) and uCmC (5’u with 3’m).ResultsPatients with paranoid schizophrenia show highly significant changes in LINE-1 partial methylation patterns, namely a higher % mCuC and lower % uCmC as compared with controls and MIP patients, while the latter show higher % mCuC but lower % uCmC as compared with controls. Higher % mCuC significantly predicts paranoid schizophrenia with a sensitivity of 51.6%, specificity of 97.5% and an area under the ROC curve of 0.895.ConclusionsThe results indicate that a common dysfunction in LINE-1 partial methylation may underpin both paranoid schizophrenia and MIP and that this methylation pattern is significantly more expressed in paranoid schizophrenia than MIP. Reciprocal links between impairments in LINE-1 methylation and neuro-immune and neuro-oxidative pathways may underpin the pathophysiology of both MIP and paranoid schizophrenia.

scholarly journals Centralized surveillance of hydatidiform mole: 7-year experience from a regional hospital in China

2021 ◽  
pp. ijgc-2021-002797
Author(s):  
Lanzhou Jiao ◽  
Yaping Wang ◽  
Jiyong Jiang ◽  
Xiuying Wang ◽  
Wenqing Zhang ◽  
...  
Keyword(s):  
High Risk ◽  
Hydatidiform Mole ◽  
Single Agent ◽  
Regional Hospital ◽  
Low Risk ◽  
Gestational Trophoblastic Neoplasia ◽  
Complete Hydatidiform Mole ◽  
Gynecology And Obstetrics ◽  
Prophylactic Chemotherapy ◽  
Hydatidiform Moles

ObjectiveTo assess the strategy and value of centralized surveillance of hydatidiform mole at a regional hospital in China and to investigate the necessity of prophylactic chemotherapy for high-risk complete hydatidiform mole.MethodsBetween February 2013 and February 2020, all women with hydatidiform mole in Dalian Women’s and Children’s Medical Center (Group) were registered for surveillance and treatment when indicated. Women with complete hydatidiform mole were categorized into low-risk and high-risk groups according to the criteria from Song Hongzhao’s trophoblastic neoplasia. Outcomes and treatments were analyzed retrospectively.ResultsIn total, 703 women with hydatidiform mole were registered for surveillance with a follow-up rate of 97.9% (688/703). 680 women were enrolled and 52 (7.6%) developed post-molar gestational trophoblastic neoplasia, all with low-risk International Federation of Gynecology and Obstetrics (FIGO) scores 0–5. Post-molar gestational trophoblastic neoplasia was diagnosed in 12.3% (51/413) of patients with complete hydatidiform moles and 0.4% (1/263) of patients were diagnosed with partial hydatidiform moles (χ2=32.415, p<0.001). Post-molar gestational trophoblastic neoplasia was diagnosed in 27.7% (28/101) of the high-risk complete hydatidiform mole group and in 7.4% (23/312) of the low-risk complete hydatidiform mole group (χ2=29.196, p<0.001). No difference in the pre-treatment assessments of patients with post-molar gestational trophoblastic neoplasia was found between the low-risk and high-risk complete hydatidiform mole groups (all p>0.05). All 52 patients with post-molar gestational trophoblastic neoplasia were cured, with a complete response rate of 61.2% (30/49) with first-line single-agent chemotherapy.ConclusionsA centralized hydatidiform mole surveillance program is feasible and effective and may improve the prognosis of patients with post-molar gestational trophoblastic neoplasia. Prophylactic chemotherapy is not recommended for women with high-risk complete hydatidiform mole with adequate surveillance.

scholarly journals MicroRNA Expression Profiling in Hydatidiform Mole for the Prediction of Postmolar GTN

2022 ◽  
Vol 21 ◽  
pp. 153303382110673
Author(s):  
Chinachote Teerapakpinyo ◽  
Wilasinee Areeruk ◽  
Patou Tantbirojn ◽  
Vorapong Phupong ◽  
Shanop Shuangshoti ◽  
...  
Keyword(s):  
Pilot Study ◽  
Expression Profiling ◽  
Case Control Study ◽  
Hydatidiform Mole ◽  
Case Control ◽  
Microrna Expression ◽  
Differentially Expressed ◽  
Gestational Trophoblastic Neoplasia ◽  
Hydatidiform Moles ◽  
Control Study

Objectives: The primary aim of the study was to identify miRNAs that were differentially expressed between complete hydatidiform moles (CHMs) that turned out to be gestational trophoblastic neoplasia (GTN) [GTN moles] and CHMs that regressed spontaneously after evacuation [remission moles]. The secondary aim was to study the profiles of miRNA expressions in CHMs. Methods: A case-control study was conducted on GTN moles and remission moles. We quantitatively assessed the expression of 800 human miRNAs from molar tissues using Nanostring nCounter. Results: From a pilot study, 21 miRNAs were significantly downregulated in GTN moles compared to the remission moles. Five of them (miR-566, miR-608, miR-1226-3p, miR-548ar-3p and miR-514a-3p) were downregulated for >4 folds. MiR-608 was selected as a candidate for further analysis on 18 CHMs (9 remission moles and 9 GTN moles) due to its striking association with malignant formation. MiR-608 expression was slightly lower in GTN moles compared to the remission moles, that is, 2.22 folds change [p = 0.063]. Conclusion: We identified 21 miRNAs that were differentially expressed between GTN moles and remission moles suggesting that miRNA profiles can distinguish between the two groups. Although not reaching statistically significant, miR-608 expression was slightly lower in GTN moles compared to remission moles.

scholarly journals When a vesicular placenta meets a live fetus: case report of twin pregnancy with a partial hydatidiform mole

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Minhuan Lin ◽  
Jinzhu Chen ◽  
Bing Liao ◽  
Zhiming He ◽  
Shaobin Lin ◽  
...  
Keyword(s):  
Twin Pregnancy ◽  
Hydatidiform Mole ◽  
First Trimester ◽  
Molar Pregnancy ◽  
Amniotic Cavity ◽  
Individualized Care ◽  
Partial Mole ◽  
Live Fetus ◽  
Hydatidiform Moles

Abstract Background Hydatidiform moles exhibit a distinctive gross appearance of multiple vesicles in the placenta. The advances in cytogenetic technologies have helped uncover novel entities of hydatidiform moles and enabled elaborate diagnoses. However, management of a vesicular placenta with a coexistent live fetus poses a bigger challenge beyond hydatidiform moles. Case presentation A 33-year-old woman was referred to our department for suspected hydatidiform mole coexistent with a live fetus at 24 weeks’ gestation. The patient had conceived through double embryo transplantation, and first-trimester ultrasonography displayed a single sac. Mid-trimester imaging findings of normal placenta parenchyma admixed with multiple vesicles and a single amniotic cavity with a fetus led to suspicion of a singleton partial molar pregnancy. After confirmation of a normal diploid by amniocentesis and close surveillance, the patient delivered a healthy neonate. Preliminary microscopic examination of the placenta failed to clarify the diagnosis until fluorescence in situ hybridization showed a majority of XXY sex chromosomes. The patient developed suspected choriocarcinoma and achieved remission for 5 months after chemotherapy, but relapsed with suspected intermediate trophoblastic tumor. Conclusion We report a rare case of twin pregnancy comprising a partial mole and a normal fetus that resembled a singleton partial molar pregnancy. Individualized care is important in conditions where a vesicular placenta coexists with a fetus. We strongly recommend ancillary examinations in addition to traditional morphologic assessment in such cases.

scholarly journals Prevalence and Factors Associated with Hydatidiform Mole among Patients Undergoing Uterine Evacuation at Mbarara Regional Referral Hospital

2018 ◽  
Vol 2018 ◽  
pp. 1-7
Author(s):  
Olivier Mulisya ◽  
Drucilla J. Roberts ◽  
Elizabeth S. Sengupta ◽  
Elly Agaba ◽  
Damaris Laffita ◽  
...  
Keyword(s):  
Gestational Age ◽  
Maternal Age ◽  
Hydatidiform Mole ◽  
Advanced Maternal Age ◽  
First Trimester ◽  
Complete Hydatidiform Mole ◽  
Regional Referral Hospital ◽  
Factors Associated ◽  
History Of ◽  
Hydatidiform Moles

Objective. We sought to determine the prevalence of and factors associated with hydatidiform molar gestations amongst patients undergoing uterine evacuation at Mbarara Regional Referral Hospital (MRRH), Mbarara, Uganda. Methods. This was a cross-sectional study carried out from November 2016 to February 2017. All patients admitted for uterine evacuation for nonviable pregnancy were included. The study registered 181 patients. Data were collected on sociodemographics, medical conditions, obstetrics, and gynecological factors. The evacuated tissue received a full gross and histopathologic examination. Cases of pathologically suspected complete hydatidiform mole were confirmed by p57 immunohistochemistry. Data were analyzed using STATA 13. Results. The prevalence of hydatidiform mole was 6.1% (11/181). All detected moles were complete hydatidiform moles, and there were no diagnosed partial hydatidiform moles. Clinical diagnosis of molar pregnancy was suspected in 13 patients, but only 69.2% (9/13) were confirmed as molar pregnancies histologically. Two cases were clinically unsuspected. Factors that had a significant relationship with complete hydatidiform mole included maternal age of 35 years and above (aOR 13.5; CI: 1.46–125.31; p=0.00), gestational age beyond the first trimester at the time of uterine evacuation (aOR 6.2; CI: 1.07–36.14; p=0.04), and history of previous abortion (aOR 4.3; CI: 1.00–18.57; p=0.05). Conclusion. The prevalence of complete hydatidiform mole was high at 6.1%. Associated risk factors included advanced maternal age (35 years and above), history of previous abortions, and gestational age beyond the first trimester at the time of evacuations. Recommendations. We recommend putting in place capacity to do routine histopathological examination of all products of conception especially those at high risk for a molar gestation either by clinical suspicion or by risk factors including advanced maternal age, advanced gestational age, and history of previous abortion because of high prevalence of complete mole.

scholarly journals Gestational Trophoblastic Neoplasia after Ectopic Molar Pregnancy: Clinical, Diagnostic, and Therapeutic Aspects

2018 ◽  
Vol 40 (05) ◽  
pp. 294-299 ◽  
Author(s):  
Consuelo López ◽  
Vania Lopes ◽  
Fabiana Resende ◽  
Jessica Steim ◽  
Lilian Padrón ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Fallopian Tube ◽  
Present Report ◽  
Hydatidiform Mole ◽  
Rare Condition ◽  
Molar Pregnancy ◽  
Gestational Trophoblastic Neoplasia ◽  
The Past ◽  
Cure Rates ◽  
Hydatidiform Moles

AbstractThis report presents the case of a patient with gestational trophoblastic neoplasia after a partial hydatidiform mole formed in the Fallopian tube. Ectopic molar pregnancy is a rare condition, with an estimated incidence of 1 in every 20,000 to 100,000 pregnancies; less than 300 cases of it have been reported in the Western literature. The present report is important because it presents current diagnostic criteria for this rare condition, which has been incorrectly diagnosed in the past, not only morphologically but also immunohistochemically. It also draws the attention of obstetricians to the occurrence of ectopic molar pregnancy, which tends to progress to Fallopian tube rupture more often than in cases of ectopic non-molar pregnancy. Progression to gestational trophoblastic neoplasia ensures that patients with ectopic molar pregnancy must undergo postmolar monitoring, which must be just as thorough as that of patients with intrauterine hydatidiform moles, even if chemotherapy results in high cure rates.

Examination of the dynamics of global DNA methylation pattern establishment during spermatogenesiss

2007 ◽  
Vol 30 (4) ◽  
pp. 90
Author(s):  
Kirsten Niles ◽  
Sophie La Salle ◽  
Christopher Oakes ◽  
Jacquetta Trasler
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Epigenetic Modification ◽  
Methylation Pattern ◽  
Chromosome 9 ◽  
Specific Gene ◽  
Global Methylation ◽  
Dna Methylation Pattern ◽  
Methylation Patterns

Background: DNA methylation is an epigenetic modification involved in gene expression, genome stability, and genomic imprinting. In the male, methylation patterns are initially erased in primordial germ cells (PGCs) as they enter the gonadal ridge; methylation patterns are then acquired on CpG dinucleotides during gametogenesis. Correct pattern establishment is essential for normal spermatogenesis. To date, the characterization and timing of methylation pattern acquisition in PGCs has been described using a limited number of specific gene loci. This study aimed to describe DNA methylation pattern establishment dynamics during male gametogenesis through global methylation profiling techniques in a mouse model. Methods: Using a chromosome based approach, primers were designed for 24 regions spanning chromosome 9; intergenic, non-repeat, non-CpG island sequences were chosen for study based on previous evidence that these types of sequences are targets for testis-specific methylation events. The percent methylation was determined in each region by quantitative analysis of DNA methylation using real-time PCR (qAMP). The germ cell-specific pattern was determined by comparing methylation between spermatozoa and liver. To examine methylation in developing germ cells, spermatogonia from 2 day- and 6 day-old Oct4-GFP (green fluorescent protein) mice were isolated using fluorescence activated cell sorting. Results: As compared to liver, four loci were hypomethylated and five loci were hypermethylated in spermatozoa, supporting previous results indicating a unique methylation pattern in male germ cells. Only one region was hypomethylated and no regions were hypermethylated in day 6 spermatogonia as compared to mature spermatozoa, signifying that the bulk of DNA methylation is established prior to type A spermatogonia. The methylation in day 2 spermatogonia, germ cells that are just commencing mitosis, revealed differences of 15-20% compared to day 6 spermatogonia at five regions indicating that the most crucial phase of DNA methylation acquisition occurs prenatally. Conclusion: Together, these studies provide further evidence that germ cell methylation patterns differ from those in somatic tissues and suggest that much of methylation at intergenic sites is acquired during prenatal germ cell development. (Supported by CIHR)

scholarly journals Gestational trophoblastic neoplasia: Retrospective analysis of clinical profile, treatment pattern and outcome

2016 ◽  
Author(s):  
Paramjeet Kaur ◽  
Ashok K. Chauhan ◽  
Anil Khurana ◽  
Yashpal Verma ◽  
Nupur Bansal
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Hydatidiform Mole ◽  
Single Agent ◽  
High Risk Group ◽  
Treatment Pattern ◽  
Gestational Trophoblastic Neoplasia ◽  
Trophoblastic Tumor ◽  
Villous Trophoblast ◽  
Invasive Mole

Background: Gestational trophoblastic disease is a spectrum of cellular proliferation arising from the placental villous trophoblast. Gestational triphoblastic neoplasia (GTN) is a collective term for GTD that invade locally or metastasize. GTD includes hydatidiform mole (complete and partial) and GTN include invasive mole, choricocarcinoma, placental site trophoblastic tumor and epitheliod trophoblastic tumor. Aim: To evaluate clinicopathological profile, treatment pattern and clinical outcome in patients with gestational trophoblastic neoplasia (GTN). Materials and Methods: Twelve cases of gestational trophoblastic neoplasia treated between 2012 to November 2015 in deptt of Radiotherapy – II, PGIMS, Rohtak were evaluated in this retrospective study. Data was analyzed on the basis of age, histopathology, stage, type of treatment received and treatment related toxicities. Disease free survival was estimated. Results: Out of 12 women 7 (58 %) had hydatidiform mole, 4 (33%) invasive mole and 01 (8%) had choriocarcinoma. All the cases were given chemotherapy. Two patients had low risk disease. Among high risk group seven patients had score of less than 7 and five patients had risk score of 7 or higher. Five patients were given single agent methotrexate, seven patients received multidrug regimens. All patients are on regular follow up. One patient (high risk group) expired as she did not receive treatment. Conclusion: GTN are rare and proliferative disorders with proper diagnosis and treatment most of the cases are amenable to treatment with favorable outcome.

Maternal Serum EG-VEGF as A First Trimester Predictor of Hypertensive Disorders of Pregnancy: A Prospective Cohort Study

2021 ◽  
Author(s):  
Shiyu Zeng ◽  
Ling Yu ◽  
Yiling Ding ◽  
Mengyuan Yang
Keyword(s):  
Cohort Study ◽  
Growth Factor ◽  
Prediction Model ◽  
Pregnant Women ◽  
Predictive Value ◽  
Prospective Cohort ◽  
First Trimester ◽  
Hypertensive Disorders Of Pregnancy ◽  
Hypertensive Disorders ◽  
Sensitivity Specificity

Abstract Background This study aims to explore whether plasma endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in the first trimester can be used as a predictor of hypertensive disorders of pregnancy (HDP), and compare it with placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) to evaluate its prediction of HDP value. Methods This is a prospective cohort study that records the medical history of the pregnant women included in the study at 11–13 weeks’ gestation, and analyzes serum biochemical markers including EG-VEGF, PIGF, sFlt-1 and sFlt-1/PIGF. The predictive values of these tests were determined. We used the receiver operating characteristic (ROC) curve to find the optimal cut-off value for each biomarker and compare the operating characteristics (sensitivity, specificity). Logistic regression analysis was used to create a prediction model for HDP based on maternal characteristics and maternal biochemistry. Results Data were obtained from 205 pregnant women. 17 cases were diagnosed with HDP, the incidence rate was 8.2% (17/205). Women who developed HDP had a significantly higher body mass index (BMI) and mean arterial pressure (MAP). Serum EG-VEGF levels in the first trimester are significantly higher in pregnant women with HDP. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value(NPV) of serum EG-VEGF levels more than 227.83 pg/ml for predicting HDP were 43%, 93%, 86% and 62%, respectively. We established a prediction model in the first trimester include maternal BMI, MAP, and EG-VEGF, with an AUC of 0.8861 (95%CI: 0.7905–0.9818), which is better than using EG-VEGF alone (AUC: 0.66). Conclusion This study demonstrated that serum EG-VEGF is a promising biomarker for predicting HDP in the first trimester. It has better predictive performance compared with the currently used biomarkers like PIGF and sFlt-1. Combining maternal clinical characteristics and biochemical tests at 11–13 weeks can effectively identify women at high risk of HDP.

Gestational Trophoblastic Neoplasia From Genetically Confirmed Hydatidiform Moles: Prospective Observational Cohort Study

2018 ◽  
Vol 28 (9) ◽  
pp. 1772-1780 ◽  
Author(s):  
Hirokazu Usui ◽  
Jia Qu ◽  
Asuka Sato ◽  
Zijun Pan ◽  
Akira Mitsuhashi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Laboratory Data ◽  
Spontaneous Remission ◽  
Observational Cohort Study ◽  
Polymorphism Analysis ◽  
Prospective Observational Cohort Study ◽  
Gestational Trophoblastic Neoplasia ◽  
Observational Cohort ◽  
Hydatidiform Moles

ObjectiveThe aim of this study was to evaluate the incidence and risk factors of gestational trophoblastic neoplasia (GTN) from hydatidiform moles (HMs) cytogenetically diagnosed in a prospective cohort setting.MethodsThe prospective observational cohort study included cases of cytogenetically defined molar pregnancies, which were diagnosed by a multiplex short tandem repeat polymorphism analysis. Cases were classified as androgenetic complete HMs (CHMs), diandric monogynic triploid partial HMs (PHMs), or biparental abortion. Gestational trophoblastic neoplasia was diagnosed according to the International Federation of Gynecology and Obstetrics 2000 criteria. Incidences for each category, that is, CHM, PHMs, and biparental abortion, were calculated. Clinical variables (age, partner age, gravidity, parity, height, weight, BMI, and gestational age) and laboratory data (serum human chorionic gonadotropin [hCG], white blood cell count, hemoglobin, and platelet count) were compared between spontaneous remission cases and GTN cases in androgenetic CHMs.ResultsAmong 401 cases, 380 were classified as follows: 232 androgenetic CHMs, 60 diandric monogynic PHMs, and 88 biparental abortions. A total of 35 cases (15.1%) of CHMs, but only 1 case of PHM (1.7%) and no biparental abortions, exhibited progression to GTN. The hCG value before evacuation was significantly higher in GTN cases than in spontaneous remission cases (P = 0.001, Kruskal-Wallis test). Patient age was also significantly higher in GTN cases than in spontaneous remission cases (P = 0.002, Student t test).ConclusionsUnder the cohort cytogenetic diagnosis setting, the traditional risk factors for GTN after molar pregnancy, hCG value before evacuation and age, were confirmed in androgenetic CHMs. The risk of GTN was lower for PHMs than for CHMs. However, 1 patient with cytogenetic PHMs developed into GTN.

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