National Cancer Institute®
Last Modified: October 1, 2002
UI - 2044074
AU - Palmer JR
TI - Oral contraceptive use and gestational choriocarcinoma.
SO - Cancer Detect Prev 1991;15(1):45-8
AD - Slone Epidemiology Unit, Boston University School of Medicine, Brookline, MA 02146.
Substantial advances have occurred in the treatment of gestational trophoblastic disease, but little is known about the etiology. Routine screening of data from a case-control study of several diseases revealed an association between gestational choriocarcinoma and oral contraceptive (OC) use. A detailed analysis of 23 cases of gestational choriocarcinoma, 34 of invasive hydatidiform mole, and 49 of hydatidiform mole, each matched on age and geographic area to 4 controls who had been pregnant at least once, was carried out. Relative to women who had never used oral contraceptives, the estimated relative risk of choriocarcinoma for women who had used oral contraceptives for at least 5 years was 6.0 (95% CI, 1.3 to 28); for invasive mole and hydatidiform mole, the relative risks were elevated but not statistically significant. Oral contraceptive use has also been associated with an increased risk of gestational choriocarcinoma in a recent study conducted in the western U.S. These findings raise the hypothesis that long-term oral contraceptive use, or a correlate of use such as exposure to sexually transmitted infections, increases the risk of one or more of the manifestations of gestational trophoblastic disease.
UI - 2068488
AU - Pinet C; Colau JC
TI - [Use of sulprostone in the evacuation of molar pregnancies]
SO - Rev Fr Gynecol Obstet 1991 Jan;86(1):53-5
AD - Service de Gynecologie-Obstetrique, Hopital Foch, Suresnes.
The diagnosis of molar pregnancy is now easy based upon a triple clinical, laboratory and ultrasonographic approach. Histology provides final confirmation. However treatment is more difficult since uterine evacuation may be very hemorrhagic or traumatic. A clinical case forms the basis here for a review of the main features concerning the diagnosis and treatment of hydatidiform mole.
UI - 7403332
AU - Keirse MJ
TI - Termination of molar pregnancy by intramuscular administration of 15(S)-15-methyl-prostaglandin F2 alpha.
SO - Prostaglandins Med 1980 May;4(5):333-9
Eleven patients entered a multicentre trial of repeated intramuscular injections of 15(S)-15-methyl-prostaglandin F2 alpha (15-me-PGF2 alpha) for terminating molar pregnancy. Duration of pregnancy ranged from 9 to 24 (median: 16) weeks and uterine size from 15 to 24 (median: 19) weeks. Complete (n=5) or incomplete (n=4) expulsion of molar tissue occurred in 9 patients (82%) after a median duration of 15.7 hours. In the remaining 2 patients treatment was interrupted after 8 hours at a cervical dilatation of 1 cm or more. Gastro-intestinal side effects were prominent in 64%. The use of prostaglandins in the management of hydatidiform mole is discussed.
UI - 7027540
AU - Gal D; Simpson ER; Porter JC; MacDonald PC; Buchsbaum HJ
TI - Failure of contraceptive steroids to modify human chorionic gonadotrophin secretion by hydatidiform mole tissue and choriocarcinoma cells in culture.
SO - Steroids 1981 Jun;37(6):663-71
The effect of steroids contained in oral contraceptives, namely ethinylestradiol:17 alpha-ethinyl-1,3,5,(10)-estratriene-3, 17-diol (E) and norethindrone acetate:17 beta-acetoxy-17-ethinyl-4-estren-3-one (N), on cell replication and human chorionic gonadotropin (hCG) secretion by choriocarcinoma cells in monolayer culture and by hydatidiform mole tissue maintained in organ culture were studied. The steroids were added to the culture medium individually or in combination to achieve a range of concentrations (10-10 to 10-4), within and beyond the presumed concentration of these substances in the blood of women taking oral contraceptives. The effect of luteinizing hormone releasing hormone (LHRH) on hCG secretion by choriocarcinoma cells in monolayer culture also was investigated. The rate of hCG production by either choriocarcinoma cells in monolayer culture or by hydatidiform mole tissue maintained in organ culture was not affected by the hormones used in this study; indeed hCG secretion remained reasonably unchanged even with high concentrations of steroids (up to 10-4 M) or LHRH (up to 10-4 mg x ml-1). Cell replication, as measured by increase in amount of cellular protein and DNA, was not stimulated by either of these compounds.
UI - 2580438
AU - Morrow P; Nakamura R; Schlaerth J; Gaddis O Jr; Eddy G
TI - The influence of oral contraceptives on the postmolar human chorionic gonadotropin regression curve.
SO - Am J Obstet Gynecol 1985 Apr 1;151(7):906-14
This article reports a retrospective analysis of 149 evaluable cases of molar pregnancy managed at Women's Hospital, Los Angeles County/University of Southern California Medical Center, from January 1977, through June, 1983. In the 84 cases prior to 1981, the patients received estrogen-progestogen oral contraceptives after evacuation while the 55 patients seen after that used nonhormonal contraceptives. The frequency of abnormal regression of the serum beta-subunit of human chorionic gonadotropin in the two groups was not significantly different (22.6% in the hormonal contraception group versus 34.5% in the nonhormonal contraception group). The groups were compared for known and potential risk factors and were nearly identical with respect to patient age, parity, maternal blood type, and race. There were also no significant differences with respect to uterine size, preevacuation beta-subunit of human chorionic gonadotropin serum titer greater than 100,000 mIU/ml, and frequency of theca-lutein cysts. Gestational age was significantly shorter and the frequency of cases with a preevacuation beta-subunit of human chorionic gonadotropin serum titer greater than 250,000 mIU/ml significantly higher in the nonhormonal contraception group, indicating that the nonhormonal contraception group had a higher risk for abnormal human chorionic gonadotropin regression than the hormonal contraception group. We conclude that this study provides no evidence that the use of estrogen-progestogen oral contraceptives prior to human chorionic gonadotropin remission increases the risk for invasive mole or choriocarcinoma following molar pregnancy.
UI - 2990199
AU - La Vecchia C; Franceschi S; Parazzini F; Fasoli M; Decarli A; Gallus G;
TI - Tognoni G Risk factors for gestational trophoblastic disease in Italy.
SO - Am J Epidemiol 1985 Mar;121(3):457-64 factors for gestational trophoblastic disease in a case-control study of 100 women with trophoblastic tumors (17 partial hydatidiform moles, 63 complete moles, and 20 choriocarcinomas) and 200 age-matched controls admitted for normal deliveries to university or general hospitals in Lombardy, Northern Italy. Questions were asked about each patient's general life-style, and medical, obstetric, menstrual, contraceptive, and social history. The risk of trophoblastic disease increased with increasing paternal age: women whose husbands were aged 40-44 years and 45 years or more had a relative risk of 2.4 and 4.2, respectively, compared to women married to men aged under 40 years. This association was independent of maternal age. Cigarette smoking was associated with trophoblastic tumors (relative risk estimate for smokers vs. never smokers = 2.0, 95% confidence interval = 1.2-3.2), the risk being greater for women who smoked more cigarettes and for longer. The effect of cigarette smoking was not explained by any other identified potential distorting factor. A positive history of fertility problems or difficulties in conception and a personal or family history of gestational trophoblastic disease were more common among the cases. Past use of oral contraceptives was not related to the risk of trophoblastic tumors, but use of an intrauterine device was significantly more common among the cases. The findings give epidemiologic support to the evidence of an androgenetic role in the origin of hydatidiform mole; moreover, they provide new hypotheses on the risk factors for gestational trophoblastic disease in developed countries. Further exploration of these factors may lead to a more coherent body of evidence on the etiology of these diseases.
UI - 2992274
AU - Parazzini F; La Vecchia C; Pampallona S; Franceschi S
TI - Reproductive patterns and the risk of gestational trophoblastic disease.
SO - Am J Obstet Gynecol 1985 Aug 1;152(7 Pt 1):866-70
The relation between reproductive pattern and the risk of gestational trophoblastic disease was evaluated in a case-control study conducted in Northern Italy on 310 women with histologically confirmed gestational trophoblastic disease and two control groups consisting of 290 obstetric subjects and 394 patients in hospital for acute, nonobstetric, nongynecologic conditions. Compared to that for nulliparous women, the estimated age-adjusted relative risk of trophoblastic disease for parous women was 0.6 (90% confidence limit = 0.4 to 0.9) when obstetric controls were used as a comparison group and 0.4 (95% confidence limit = 0.2 to 0.6) compared with other controls. Conversely, a history of spontaneous abortions was associated with elevated risk of gestational trophoblastic disease, and the risk increased significantly with increasing number of spontaneous abortions. When the combined effect of parity and spontaneous abortions was considered, the major factor influencing the risk of gestational trophoblastic disease was the existence of one or more previous term pregnancies.
UI - 6849356
AU - Ho Yuen B; Burch P
TI - Relationship of oral contraceptives and the intrauterine contraceptive devices to the regression of concentrations of the beta subunit of human chorionic gonadotropin and invasive complications after molar pregnancy.
SO - Am J Obstet Gynecol 1983 Jan 15;145(2):214-7
One hundred ninety-four patients with pathologically confirmed molar pregnancy and intact uteri were studied prospectively. Group A included 177 patients in whom the beta subunit of human chorionic gonadotropin (hCG-beta) declined to normal (less than 5 mlU/ml) without chemotherapy, whereas group B included 17 patients with invasive complications in the postmolar phase which necessitated the use of chemotherapy. Only women with intact uteri were included in the study. In group A, there were no significant differences in the human chorionic gonadotropin (hCG) positive interval between women who used intrauterine contraceptive devices, barrier and other methods, and those who used oral contraceptives. Differences in the proportions of women in groups A and B who used the oral contraceptives and intrauterine contraceptive devices were not observed. However, the mean dosage of estrogen and the proportion of women who ingested more than 50 micrograms of estrogen were higher in group B. These data suggest that (1) the oral contraceptives with less than 50 micrograms of estrogen and the intrauterine contraceptive devices do not prolong the hCG-beta positive interval nor increase the risk of invasive complications in the postmolar phase which requires the use of chemotherapy; and (2) the dose of estrogen (in formulations that contain more than 50 micrograms) rather than the oral contraceptives per se may influence the risk of these postmolar complications.
UI - 6684883
AU - Martin BR 3rd; Orr JW Jr; Austin JM Jr
TI - Cervical choriocarcinoma associated with an intrauterine contraceptive device: a case report.
SO - Am J Obstet Gynecol 1983 Oct 1;147(3):343-4
UI - 3287245
AU - Pandiyan N; Jequier AM
TI - Postmolar contraception.
SO - Obstet Gynecol Surv 1988 May;43(5):258-62
AD - Department of Obstetrics & Gynaecology, University of Nottingham, University Hospital, Queen's Medical Centre, U.K.
Recent studies on the etiology and the cytogenetics of trophoblastic tumors suggest that hydatidiform mole and choriocarcinoma may be conditions with no causal relationship. With the advent of newer diagnostic methods which aid in the early diagnosis of pregnancy and help to differentiate it from abnormal pregnancy together with the increasing concern over the safety of use of the contraceptive measures following a hydatidiform mole, it is suggested that a period of postmolar contraception may no longer be necessary. The follow-up of these patients should include serial sonography in association with other currently available methods. Pregnancy should also be allowed to occur naturally if the patient so desires.
UI - 2848605
AU - Smith DB; Rustin GJ; Bagshawe KD
TI - Don't ignore a positive pregnancy test.
SO - BMJ 1988 Oct 29;297(6656):1119-20
AD - Department of Medical Oncology, Charing Cross Hospital, London.
UI - 9649918
AU - Vartiainen J; Alfthan H; Lehtovirta P; Stenman UH
TI - Identification of choriocarcinoma by the hCG beta-to-hCG proportion in patients with delayed diagnosis caused by contraceptive use.
SO - Contraception 1998 Apr;57(4):257-60
AD - Department of Obstetrics, Helsinki University Central Hospital, Finland.
The use of contraceptives, especially subdermal implants and levonorgestrel-containing intrauterine device (IUD), often cause irregular bleeding. Thus, they may mask unsuspected choriocarcinoma, which also often presents with abnormal bleeding. Choriocarcinoma is mostly curable with combination chemotherapy, but delayed diagnosis can lead to treatment failure. Two cases of choriocarcinoma with considerable delay in diagnosis, due partly to contraceptive use, are reported. The proportion of human chorionic gonadotropin-beta (hCG beta) and total hCG immunoreactivity showed that the proportion of hCG beta was elevated at presentation in both cases.
UI - 11254939
AU - Easterfield AJ; Austen BM; Westwood OM
TI - Inhibition of antigen transport by expression of infected cell peptide 47 (ICP47) prevents cell surface expression of HLA in choriocarcinoma cell lines.
SO - J Reprod Immunol 2001 Apr;50(1):19-40
AD - Division of Immunology, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK.
Cell surface expression of HLA class I (including non-classical HLA-G) in JEG3 (choriocarcinoma cell line) was blocked by stable transfection with the sequence encoding the Herpes simplex virus protein, infected cell peptide 47 (ICP47) inserted into a vector pCEP4. Intracellular expression of ICP47 protein in ICP47-transfected cells was demonstrated. The lack of HLA cell surface expression was likely to be due to blockage of peptide transport from the cytoplasm into the endoplasmic reticulum by ICP47. ICP47 is known to block the heterodimeric transporter associated with antigen processing (formed from TAP1 and TAP2). Western blotting with a polyclonal antibody to the C-terminus of TAP1 showed high expression of TAP1 in BeWo and JEG3, but not JAR cells, expression that was strongly upregulated by gamma-interferon. Gamma-interferon also upregulated the cell surface expression of HLA class I. TAP1 was strongly expressed in MC2 and MC3 extravillous cytotrophoblast cell lines immortalised with the SV40 large T antigen. The results suggest a role for non-classical HLA in the presentation of antigenic peptides to the immune system.
UI - 12006530
AU - Agarwal R; Strickland S; McNeish IA; Patel DC; Foskett M; Boultbee JE;
TI - Newlands ES; Seckl MJ Doppler ultrasonography of the uterine artery and the response to chemotherapy in patients with gestational trophoblastic tumors.
SO - Clin Cancer Res 2002 May;8(5):1142-7
AD - Department of Health Gestational Trophoblastic Disease Unit, Charing Cross Hospital Campus, Imperial College, London W6 8RF, United Kingdom.
PURPOSE: Increasing new blood vessel formation (neoangiogenesis) within tumors is an adverse prognostic factor for survival in several cancers. Neoangiogenesis is usually determined histopathologically and not in vivo. To assess neoangiogenesis in vivo, we have used Doppler ultrasonography (US) to measure the uterine artery pulsatility index (UAPI) in patients with gestational trophoblastic tumors (GTTs). Here, we assess whether the UAPI can provide independent prognostic information predictive of methotrexate resistance (MTX-R), a drug central to the management of GTT. EXPERIMENTAL DESIGN: All patients reviewed to determine their pretreatment Charing Cross Hospital (CXH) prognostic score, uterine volume, the lowest UAPI of either uterine artery, number of metastases, and human chorionic gonadotropin (hCG) concentration. Of the 164 patients for whom all data were available, 47 subsequently developed MTX-R, defined as a plateaued or rising hCG in two consecutive samples. RESULTS: UAPI, hCG, uterine volume, presence of metastases, and the overall CXH prognostic score were all predictive of MTX-R on univariate analysis. Moreover, the UAPI remained a significant independent predictor of MTX-R on multiple logistic regression analysis. After adjustment for the CXH prognostic score, the odds ratio for the risk of MTX-R in patients with a UAPI < or =1 compared with those with a UAPI >1 was 2.68 (95% confidence interval, 1.25-5.74; P = 0.01). The unadjusted odds ratio for the above comparison was 2.32 (95% confidence interval, 1.14-4.7; P = 0.02). CONCLUSIONS: The UAPI, as an indirect in vivo measure of functional tumor vascularity, independently predicts the response to chemotherapy in GTTs.
UI - 12183814
AU - Loukovaara M; Lehtovirta P
TI - [Trophoblastic diseases--a group of rare diseases]
SO - Duodecim 2001;117(24):2539-46; quiz 2546, 2571
AD - HUS:n naistensairaala Haartmaninkatu 2, 00290 Helsinki. email@example.com
UI - 12068171
AU - Kato HD; Terao Y; Ogawa M; Matsuda T; Arima T; Kato K; Yong Z; Wake N
TI - Growth-associated gene expression profiles by microarray analysis of trophoblast of molar pregnancies and normal villi.
SO - Int J Gynecol Pathol 2002 Jul;21(3):255-60
AD - Division of Molecular and Cell Therapeutics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Beppu City, Oita, Japan.
We used microarray analysis to investigate expression profiles of 589 known genes committed to cell growth control to characterize regulatory circuitry for cell proliferation in complete moles (CMs). CMs are characterized by hyperplastic trophoblast and have a high propensity to give rise to choriocarcinoma. Characteristic alterations in gene expression profiles were observed when compared with normal villi. Fifty-seven genes were significantly up-regulated in CMs and involved the Ras-Map kinase 3, Jak-STAT5, and Wnt signal pathways, implicating growth factor or cytokine-mediated signal pathways in the trophoblastic hyperplasia of CMs. Several genes associated with anti-apoptosis, cell structuring, and/or cell attachment were also up-regulated in CMs. In contrast, relatively fewer genes were down-regulated and these involved IGFBPs, versican, interleukin-1, tumor necrosis factor receptor, CD44, and RAD52. Genes identified in this study may elucidate regulation mechanisms of trophoblastic proliferation and mechanisms causing a pathological phenotype in CMs.
UI - 12233006
AU - Ulander VM; Ammala P; Sjoberg J; Lehtovirta P
TI - [Massive fetomaternal bleeding--an insidious and serious pregnancy complication]
SO - Duodecim 2002;118(6):621-4
AD - HUS:n naistenklinikka PL 140, 00029 HUS.
UI - 11963831
AU - Alex S; Panikkar B; Devi C; Balaram P
TI - Expression of nm23-H1 protein in relation to myometrial invasion in complete hydatidiform moles.
SO - J Soc Gynecol Investig 2002 Mar-Apr;9(2):111-5
AD - Division of Cancer Research, Regional Cancer Centre, Trivandrum, Kerala, India-695011.
OBJECTIVE: Although nm23-H1 protein expression has been related to invasion in many cancers, its expression and prognostic significance in complete hydatidiform moles has not yet been investigated. The search for biologic parameters in molar placentas, which are useful for identifying patients who show myometrial invasion of the tumor, is crucial. We examined the clinical significance of nm23-H1 expression in complete hydatidiform mole. METHODS: Sections of 105 cases of complete hydatidiform moles (including 25 cases of invasive mole) and 95 cases of gestational age--matched normal placentas were immunohistochemically stained with anti-nm23-H1 antibody, which recognizes the nm23-H1/NDP kinase A gene product. RESULTS: Expression of nm23-H1 was detected in the cytotrophoblasts and syncytiotrophoblasts of molar placentas and normal placentas, whereas it was not detected in stromal tissue. Expression of nm23-H1 showed a negative relation to invasion, suggesting its use as a potential marker of myometrial invasion in complete hydatidiform moles. CONCLUSION: nm23-H1 expression could be used as a marker for accurate evaluation of myometrial invasion in complete hydatidiform mole.
UI - 12152292
AU - Pietrzak K; Drabik M; Ziolkowska-Seta I; Bidzinski M; Tulimowski J
TI - [The clinical analysis and results of treatment of the patients with gestational trophoblastic disease]
SO - Ginekol Pol 2002 Apr;73(4):390-5
AD - Kliniki Nowotworow Narzadow Plciowych Kobiecych Centrum Onkologii Instytutu im. M. Sklodowskiej-Curie w Warszawie.
OBJECTIVES: The aim of this work was to establish the dependence between the results of treatment and clinical stage and prognostic factors of the patients with gestational trophoblastic disease. MATERIALS AND METHODS: The retrospective analysis of 1259 patients with Gestational Trophoblastic Disease (GTD) observed in years of 1977-1995 in the Maria Sklodowska-Curie Memorial Cancer and Institute of Oncology in Warsaw, Poland was made. Out of them 281 had recommendation for treatment. The mean age of the examined women was 34.5 years and treated patient 38.0 years. The clinical structure of the treated patients according to clinical stages: I--202 (72.1%), II low risk--17(6.1%), II high risk--4 (1.4%), III low risk--22 (7.9%), III high risk--26 (9.3%), IV--9 (3.2%). The clinical structure of the treated patients by histopathological type: hydatidiform mole 148 (52.7%), invasive mole 34 (12.1%), choriocarcinoma 93 (33.1%), without histopathological diagnosis 6 (2.1%). The distribution of the treated patients by antecedent pregnancy: hydatidifrom mole 166 (59.1%), spontaneous abortion 47 (16.7%), ectopic pregnancy 9 (3.2%) term delivery 59 (21%). RESULTS: Among 281 patients who received chemotherapy 79 of them underwent surgery. In the group of 281 treated patients, 267 (95%) are alive without the signs of disease, 11 (3.9%) died, 1 (0.4%) is alive with the symptoms of disease, 2 (0.7%) were lost of observation. CONCLUSIONS: 1. Among the observed patients with GTD 23% needed treatment. 2. The most common histopathological type of observed patients was hydatidiform mole. 3. General treatment of patients with GTD consists of chemotherapy. 4. The results of treatment should be seen as successful since 96.5% of patients survived 5 years. 5. Survival of patients with GTD depends on clinical stage and risk factors.
UI - 12152293
AU - Popiela A; Panszczyk M; Gabrys M
TI - [Choriocarcinoma with atypical clinical course. Case report]
SO - Ginekol Pol 2002 Apr;73(4):396-9
AD - II Kliniki Ginekologii AM we Wroclawiu.
Authors describe a case of choriocarcinoma with an atypical clinical course in 28-year old woman nine months after a normal pregnancy and labour. Diagnosis of the disease was very hard because endometrial biopsy did not show any suspected cells and two performed pregnancy tests were not positive. Diagnosis was confirmed after a hysterectomy. Authors conclude that every unclear vaginal bleeding during woman's reproductive years should be considered with a beta-HCG level measurement.
UI - 12196865
AU - Gerulath AH; Ehlen TG; Bessette P; Jolicoeur L; Savoie R; Society of
TI - Obstetricians and Gynaecologists of Canada; Gynaecologic Oncologists of Canada; Society of Canadian Colposcopists Gestational trophoblastic disease.
SO - J Obstet Gynaecol Can 2002 May;24(5):434-46
AD - Toronto, Ontario, Canada.
OBJECTIVE: To provide standards for the diagnosis and treatment of patients with hydatidiform mole and gestational trophoblastic tumours (GTT).OPTIONS: Prognostic factors useful for treatment decisions in GTT are defined with patients classified as low-, medium-, and high-risk groups.OUTCOMES: Improved mortality and morbidity.EVIDENCE: Evidence was gathered using Medline for relevant studies and articles from 1980 to 2001 with specific reference to diagnosis, treatment options, and outcomes. The quality of evidence of Recommendations has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on the Periodic Health Exam. RECOMMENDATIONS:1. Suction curettage is the preferred method of evacuation of the hydatidiform mole (III-C). Post-operative surveillance with hCG assays is essential (II-3B). 2. Low-risk patients with both non-metastatic and metastatic disease should be treated with single-agent chemotherapy, either methotrexate or dactinomycin (II-3B). 3. Medium-risk patients should usually be treated with multi-agent chemotherapy, either MAC or EMA (III-C); single-agent chemotherapy may also be used (III-C). 4. High-risk patients should be treated with multi-agent chemotherapy EMA/CO, with selective use of surgery and radiotherapy (II-3B). Salvage chemotherapy with EP/EMA and surgery should be employed in resistant disease (III-C). 5. Placental site trophoblastic tumour that is non-metastatic should be treated with hysterectomy (III-C). Metastatic disease should be treated with chemotherapy, most commonly EMA/CO (III-C).6. Women should be advised to avoid pregnancy until hCG levels have been normal for six months following evacuation of a molar pregnancy and for one year following chemotherapy for gestational trophoblastic tumour. The combined oral contraceptive pill is safe for use by women with GTT (III-C).VALIDATION: These guidelines have been reviewed and approved by the Policy and Practice Guidelines Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC), the Gynaecologic Oncologists of Canada (GOC), the Society of Canadian Colposcopists (SCC), and by Executive and Council of the SOGC.SPONSOR: The Society of Obstetricians and Gynaecologists of Canada.
UI - 10692252
AU - Halperin R; Peller S; Sandbank J; Bukovsky I; Schneider D
TI - Expression of the p53 gene and apoptosis in gestational trophoblastic disease.
SO - Placenta 2000 Jan;21(1):58-62
AD - Department of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin, Israel.
In order to understand the involvement of the p53 tumour suppressor gene in the pathogenesis of gestational trophoblastic disease (GTD), we investigated its genetic status, protein expression and its role in apoptosis in samples of complete and partial hydatidiform mole as compared with those of normal placenta. Direct sequencing of polymerase chain reaction (PCR) products of the coding and non-coding regions of the p53 gene demonstrated no mutations in any of the studied samples. Immunohistochemical studies revealed increased expression of the p53 protein predominantly in the nuclei of villous cytotrophoblasts. This over-expression of p53 was found in all samples of complete mole, in 50 per cent of partial mole samples and in about 30 per cent of normal placenta cases, although no significant difference in the staining intensity and pattern was observed. An in situ detection of DNA nicking (TUNEL) staining, demonstrating apoptosis, was also detected predominantly in villous cytotrophoblasts and in stromal areas. The per centage of apoptotic cells in all studied samples, determined by flow cytometry, demonstrated a significant increase in apoptotic cells in samples of complete and partial hydatidiform mole compared with those of normal placenta (P< 0.0003 and P< 0.004, respectively).In conclusion, the current study may provide a possible explanation to the pathogenesis of GTD, probably associated with extensive p53-dependent apoptosis to modulate excessive trophoblastic proliferation. Copyright 2000 Harcourt Publishers Ltd.
UI - 10692255
AU - Khan S; Katabuchi H; Araki M; Ohba T; Koizumi T; Okamura H; Nishimura R
TI - The molar vesicle fluid contains the beta-core fragment of human chorionic gonadotropin.
SO - Placenta 2000 Jan;21(1):79-87
AD - Department of Obstetrics and Gynecology, Kumamoto University School of Medicine, Honjo 1-1-1, Kumamoto-City, 860-8556, Japan.
The human chorionic gonadotropin (hCG) beta-core fragment (beta-CF) is a major molecular form of hCG beta subunit (hCGbeta) immunoreactivity in the urine of pregnant women and patients with trophoblastic disease. The majority of evidence supports the fact that the beta-CF is a degradative product of intact hCG and free hCGbeta in the kidneys. We found a beta-CF-like substance in the fluid of molar vesicles from a patient with complete hydatidiform mole. The molar fluid beta-CF (mbeta-CF) was indistinguishable from the beta-CF in the patient's urine (ubeta-CF) by immunoreactivity and by elution profile on gel chromatography. The binding study to lectins, however, showed that mbeta-CF contains a carbohydrate moiety that differs from that of ubeta-CF.Immunohistochemistry with anti-beta-CF antibody demonstrated a strong immunoreactivity in a large number of macrophages in the molar villous stroma. In vitro incubation of intact hCG with peritoneal macrophages showed a slow increase of intact hCG in the cell cytosol with the appearance of beta-CF-like substance in the cell supernatant. In conclusion, the source of beta-CF in molar fluid is likely to be macrophages existing in the villous stroma. Thus macrophages may ingest intact hCG and act as a local regulator of gonadotropic hormones. Copyright 2000 Harcourt Publishers Ltd.
UI - 10736255
AU - Bernus I; Mitchell AM; Manley SW; Mortimer RH
TI - Lack of membrane transport of l-thyroxine sulphate in the human choriocarcinoma cell line, JAr.
SO - Placenta 2000 Mar-Apr;21(2-3):283-5
AD - Conjoint Endocrine Laboratory, Clinical Research Centre, RBH Research Foundation and Division of Chemical Pathology, Queensland Health Pathology Service, Royal Brisbane Hospital Campus, Brisbane, Queensland, Australia. irenB@qimr.edu.au
We examined uptake of l -thyroxine sulphate (T(4)S) and possible interactions between T(4)S and thyroxine (T(4)) uptake in the choriocarcinoma cell line JAr. Cells were incubated with 50 p m(125)I-T(4)S in the absence (total uptake) and in the presence (non-specific uptake) of 10 microm T(4)S. Cells were also incubated at 37 degrees C for 2 min with 50 p m(125)I-T(4)in the presence of an increasing amount of unlabelled T(4)(0-10 microm) or T(4)S (0-30 microm). There was negligible total uptake of(125)I-T(4)S (1.14+/-0. 05 fmol/mg cellular protein, mean+/-sem) and no specific uptake after 120 min incubation. Minor inhibition of(125)I-T(4)uptake by T(4)S could be explained entirely by a low level of residual T(4)(0. 2 per cent) in the T(4)S preparation. These findings indicate that T(4)S does not share the T(4)membrane transporter. Copyright 2000 Harcourt Publishers Ltd.
UI - 10833370
AU - Fujisawa K; Nasu K; Arima K; Sugano T; Narahara H; Miyakawa I
TI - Production of interleukin (IL)-6 and IL-8 by a choriocarcinoma cell line, BeWo.
SO - Placenta 2000 May;21(4):354-60
AD - Department of Obstetrics and Gynecology, Oita Medical University, Hasama-machi, Oita, 879-5593, Japan.
To clarify the biological and pathological features of choriocarcinoma, we evaluated the in vitro production of cytokines by a choriocarcinoma cell line, BeWo. We measured the concentration of interleukin (IL)-6 and IL-8 in the culture media of BeWo cells after stimulation with various modulatory agents of cytokine expression by enzyme-linked immunosorbent assays. Northern blot analysis was used to examine the expression of IL-6 and IL-8 mRNA in these cells. A weak expression of IL-6 and IL-8 was detected in unstimulated BeWo cells by both methods. IL-6 transcription and secretion were dose-dependently enhanced by stimulation with IL-1beta, tumour necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1 and 12-O-tetradecanoyl phorbol-13-acetate (TPA). Forskolin, lipopolysaccharide and interferon-gamma had no effect on these cytokines production. The TNF-alpha-induced secretion of IL-6 was inhibited by dexamethasone. The TPA-induced production of IL-6 was inhibited by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine and sphyngosine, suggesting the involvement of a protein kinase C-dependent pathway. Levels of IL-8 mRNA and protein were also dose-dependently increased by stimulation with IL-1beta, TNF-alpha and TPA. In contrast to IL-6, the expression of IL-8 was not affected by TGF-beta1. It is suggested that, in addition to the production of steroidal and non-steroidal hormones, these cytokines may serve as part of a cytokine network that modulates the proliferation and angiogenesis of choriocarcinomas. Copyright 2000 Harcourt Publishers Ltd.
UI - 11170827
AU - Durand S; Dumur C; Flury A; Abadie P; Patrito L; Podhajcer O;
TI - Genti-Raimondi S Altered mitochondrial gene expression in human gestational trophoblastic diseases.
SO - Placenta 2001 Feb-Mar;22(2-3):220-6
AD - Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Pabellon Argentina, Ala Oeste, Ciudad Universitaria, 5000 Cordoba, Argentina.
To assess the molecular basis of phenotypic alterations present in the gestational trophoblastic diseases (GTDs) and to identify genes whose expression is specifically associated with these placental proliferative disorders we performed differential display (DD) techniques. This strategy resulted in the isolation of four mitochondrial transcripts downregulated in benign, as well as in malignant, trophoblastic diseases encoding the cytochrome oxidase subunit I (COX I), the ATPase subunit 6, the 12S ribosomal RNA (12S rRNA) and the transfer RNA for phenylalanine (tRNA(Phe)).This expression pattern was confirmed by Northern blot in normal early placenta (NEP), complete hydatidiform mole (CHM), persistent gestational trophoblastic disease (PGTD) and the human choriocarcinoma derived cell line JEG-3. Quantification of mitochondrial DNA by dot blot indicated that these changes in expression were not associated with a significant alteration in the number of mitochondrial genome. In addition, a reduction in the mitochondrial transcription factor A (mtTFA) mRNA level was observed in benign as well as in malignant trophoblastic diseases in correlation with the decrease in the mitochondrial transcript levels. Furthermore, Western blot analysis for COX-I showed a close parallelism with the expression level of the cognate RNA. Taken together, these data demonstrate that a significant change in mitochondrial transcription is associated with the phenotypic alteration present in GTDs. Copyright 2001 Harcourt Publishers Ltd.
UI - 11440542
AU - Uehara C; Ino K; Suzuki T; Kajiyama H; Kikkawa F; Nagasaka T; Mizutani S
TI - Upregulation of neutral endopeptidase expression and enzymatic activity during the differentiation of human choriocarcinoma cells.
SO - Placenta 2001 Jul;22(6):540-9
AD - Department of Obstetrics and Gynecology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Neutral endopeptidase (NEP)/CD10, a cell-surface peptidase degrading various bioactive peptides, is mainly present in syncytiotrophoblasts in the human placenta. However, the change in NEP expression upon trophoblast differentiation remains to be clarified. In the present study, we examined the expression of NEP in the differentiating trophoblast using the BeWo choriocarcinoma cell line as a model system. Under the normal culture conditions, NEP was very weakly expressed on most proliferating cytotrophoblastic BeWo cells, while a minority of the cell population (less than 5 per cent ), consisting of giant, multinucleated cells, clearly expressed NEP at the cell membrane. Treatment of BeWo cells with forskolin (FSK) for 48-72 h resulted in an 11- to 44-fold increase in the level of hCG secretion and induced cell fusion leading to the formation of multinucleated syncytiotrophoblasts, indicating functional and morphological differentiation. Fluorescence-activated cell sorting (FACS) analysis revealed that treatment with FSK significantly increased the cell-surface protein expression of NEP on differentiating BeWo cells. Consistently, there was a significant increase in the NEP enzymatic activity after FSK treatment. The level of hCG secretion from the FSK-treated cells was further enhanced when the cells were treated in the presence of the NEP inhibitor phosphoramidon. Immunohistochemical analysis of normal chorionic villi and choriocarcinoma tissues revealed the localization of NEP in syncytiotrophoblastic cells, as opposed to weak or negative staining in cytotrophoblastic cells. These data demonstrate that induction of choriocarcinoma cell differentiation is associated with an increase of NEP/CD10 expression at the cell surface, suggesting a role of this enzyme in regulating differentiated trophoblast functions such as hCG secretion. NEP/CD10 may also be a new cellular differentiation marker of both the normal and neoplastic trophoblast. Copyright 2001 Harcourt Publishers Ltd.
UI - 11597192
AU - Sebire NJ; Rees H; Paradinas F; Fisher R; Foskett M; Seckl M; Newlands E
TI - Extravillus endovascular implantation site trophoblast invasion is abnormal in complete versus partial molar pregnancies.
SO - Placenta 2001 Sep-Oct;22(8-9):725-8
AD - Department of Histopathology, Trophoblastic Disease Surveillance Unit, Charing Ross Hospital, London, UK. firstname.lastname@example.org
This study examines endovascular trophoblast invasion in pregnancies complicated by complete hydatidiform mole (CM), partial hydatidiform mole (PM) and non-molar abortions (HA). Two hundred consecutive cases from a supra-regional referral centre for suspected trophoblastic disease were examined histologically with particular regard to the presence or absence of endovascular trophoblast invasion of decidual vessels. There were 57 CM, 75 PM and 68 HA. The prevalence of normal endovascular invasion of decidual vessels was significantly lower in CM compared to all other clinical groups, amongst which there were no significant differences. Endovascular trophoblast was identified in about 80 per cent of HA and PM moles, compared to only around 25 per cent of CM (Z = -4.0, P< 0.0001). The majority of cases of complete mole demonstrated a similar appearance, of implantation site showing florid interstitial extravascular trophoblast invasion with surrounding of decidual vessels but without normal endovascular trophoblast invasion or 'plugging' seen. In many cases, there also appeared to be destruction of decidual vessels with interstitial haemorrhage and extensive fresh blood clot present in the histological sections. These findings may provide some explanation regarding the mechanism of clinical findings in molar pregnancy. Copyright 2001 Harcourt Publishers Ltd.
UI - 11718570
AU - Katsumata Y; Nomura S; Ino K; Iwanaga K; Kurosawa N; Ito T; Okada M;
TI - Tsujimoto M; Kikkawa F; Mizutani S Progesterone stimulates the expression of aminopeptidase A/angiotensinase in human choriocarcinoma cells.
SO - Placenta 2001 Nov;22(10):831-6
AD - Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Nagoya 466-8550, Japan.
In human placenta aminopeptidase A (APA), a principal enzyme that converts angiotensin II to angiotensin III, seems to be involved in angiotensin II metabolism during pregnancy. In this study, we investigated the possible effects of progesterone and estrogen on APA mRNA and protein levels in choriocarcinoma cells as a model for placenta. By RNase protection assay, progesterone induced higher APA mRNA levels than estrogen at the same concentration. Progesterone exhibited dose-dependent stimulation of APA mRNA, 1.8-fold increase at 10(-6) m for 24 h treatment. Progesterone at 10(-6) m increased APA mRNA levels within 12 h and in time-dependent fashion up to 24 h. Fluorescence-activated cell sorting analysis and measurements of APA activities revealed the induction of APA protein by progesterone. Expression of progesterone receptors (PR) and glucocorticoid receptors (GR) were determined in these cells by RT-PCR, which suggested that the progesterone's actions might be displayed through PR and/or GR. These findings may serve as a useful model to study the effects of progesterone on angiotensin II metabolism in placenta, although the physiological validity of these studies remains to be clarified. Copyright 2001 Harcourt Publishers Ltd.
UI - 6281754
AU - Lee JN; Wahlstrom T; Seppala M; Salem HT; Ouyang PC; Chard T
TI - Immunohistochemical demonstration of placental protein 5 in trophoblastic tumours.
SO - Placenta 1982 Jan-Mar;3(1):67-70
An immunoperoxidase technique was used for the detection of placental protein 5 (PP5) in tissue specimens from trophoblastic tumours. PP5 was detected in all of 15 cases of hydatidiform mole, in two out of six destructive moles and in one of seven choriocarcinomas. Though the biological importance of PP5 is not clear, its association with inactivation of plasmin suggests a role in the control of placental invasiveness.
UI - 6390422
AU - Fisher RA; Lawler SD
TI - The expression of major histocompatibility antigens in the chorionic villi of molar placentae.
SO - Placenta 1984 May-Jun;5(3):237-42
Frozen sections of chorionic villi from molar placentae, ranging in menstrual age from 9 to 19 weeks, were studied by an immunoperoxidase technique using the monoclonal antibody to HLA-A,-B,-C antigens W6/32. The distribution of class I HLA antigens in molar placentae was compared with that in normal placental tissue of comparable menstrual age. The results showed that the distribution of these antigens in molar placentae is similar to that seen in normal placentae. In both tissues, class I HLA antigens were absent from the syncytiotrophoblast and the cy