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PubMed2002

Expressions of p53, proliferating cell nuclear antigen, and Ki-67 in gestational trophoblastic diseases.

OBJECTIVE: This study was done to determine whether the expressions of p53, PCNA, and Ki-67 could differentiate spontaneous abortions with hydropic changes from gestational trophoblastic diseases. MATERIALS AND METHODS: Twenty partial hydatidiform moles, 21 complete hydatidiform moles, nine invasive hydatidiform moles, three choriocarcinomas and 19 first trimester hydropic spontaneous abortions were evaluated by means of immunohistochemical methods with antibodies to p53, PCNA, and Ki-67 in this study. RESULTS: The Ki-67, PCNA, and p53 immunoreactivity was significantly higher in the gestational trophoblastic disease group than in the spontaneous abortion group with hydropic changes. None of the three parameters provided reliable discrimination among gestational trophoblastic disease subgroups. CONCLUSION: Our findings suggest that expressions of Ki-67, proliferating cell nuclear antigen and p53 can be used to differentiate between spontaneous abortion with hydropic changes and gestational trophoblastic disease when all three markers are used together.

Abortion, Spontaneous↗
PubMed1981

[Current diagnosis and therapy of gestational trophoblastic tumors: experience with 24 patients].

Observation of 24 gestational trophoblastic tumors, i.e. 20 hydatidiform moles, 1 invasive hydatidiform mole, 1 non-metastatic and 2 metastatic choriocarcinomas, is reported. The diagnoses were based on case record data, clinical findings, echography and radioimmunoassay of human gonadotropin (HCG). The therapy was oriented towards maintaining fertility in reproductive women. For treatment with cytostatic drugs the patients were allocated to a low risk and a high risk group according to history, diagnosis and former therapy, and an appropriate mono- or combined therapy was started. 17 of 24 patients were cured by surgery in an initial therapy phase. 7 tumors were progressive, 6 of which responded to secondary surgical or cytostatic treatment. One patient died from metastases of choriocarcinoma. The total cure rate of 96% was rendered possible by regular follow-up including bimanual palpation, echography, HCG-assay and chest X-rays.

Adolescent↗
PubMed1980

[Immunological analysis of hydatidiform mole and invasive mole (author's transl)].

Thirty-two cases of hydatidiform mole without endometrial invasion of chorial tissue and 17 of invasive mole were studied to ascertain whether these two diseases can be differentiated by various immune parameters. All of hydatidiform 11 of invasive mole were sampled at a state of "mole in utero" (pre-evacuation), but 6 of invasive mole were at a post-evacuation state, respectively. The results were summarized in the following items; 1. Serum total protein, especially albumin decreased with no significant difference in both groups. Globulin fractionation (alpha 1, alpha 2, beta, gamma-globulin) showed no characteristic changes. 2. A variation of immunoglobin (IgG, IgM, IgA) was similar in both. 3. Beta 1 C (a component of complement) increased in two groups, but no difference was revealed. 4. Leucocytosis was observed, but lymphocytosis was not detected in both groups. 5. Active E-RFC slightly increased, although total E-RFC and EAC-RFC were within normal range. But these findings were not statistically different in both. 6. In vitro lymphocyte-PHA-response was fairly depressed without a significant difference in two groups. 7. Suppressive effect of serum on lymphocyte-response was also slightly strengthened, but a difference in both was not significant. 8. The results of immune skin tests (PHA, PPD, SK-SD, Candida) could not be debated with liquid numbers studied.

Blood Proteins↗
PubMedDate not supplied

HLA expression by trophoblast of invasive moles.

HLA expression by the trophoblast in invasive hydatidiform mole was analysed by immunoperoxidase staining. In the invading villi of an invasive mole, villous trophoblast, both syncytiotrophoblast and cytotrophoblast, failed to show a positive reaction for HLA-A, -B and -C and HLA-DR. By contrast, extravillous trophoblast showed an intense reaction for HLA-A, -B and -C. The distribution of HLA antigens in the invading villi was the same as in the non-invading villi, and the antigens were also indistinguishable from those noted in non-invasive hydatidiform moles. The histopathology of invasive mole may suggest that it is a malignant neoplasm. This immunohistochemical study, however, lends support to the current view that invasive mole is a variant of a benign hydatidiform mole rather than a form of malignant trophoblastic disease.

Female↗
PubMed1993

Immunohistochemical localization of inhibin-activin subunits in hydatidiform mole and invasive mole.

OBJECTIVE: To examine the cellular localization of each inhibin subunit in hydatidiform mole and invasive mole. METHODS: Tissues were collected and fixed in Bouin's solution and studied with the immunohistochemical technique avidin-biotin-peroxidase complex. RESULTS: In the villous trophoblasts of hydatidiform mole and invasive mole, distinct immunostaining for inhibin alpha-subunit was observed in proliferative syncytiotrophoblasts, but not in the cytotrophoblasts. Positive immunostaining for beta A- and beta B-subunits was observed in both syncytiotrophoblasts and cytotrophoblasts. In extravillous trophoblasts of the invasive mole, staining for beta A- and beta B-subunits was observed, whereas staining for alpha-subunit was not detected. CONCLUSION: Inhibin-activin subunits may be produced in the trophoblasts of hydatidiform mole and invasive mole, and inhibin and activin may play a role in trophoblastic proliferation and invasion.

Female↗
PubMed1991

Oral contraceptive use and gestational choriocarcinoma.

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.

Adolescent↗
PubMed1999

Mola invasiva--special form of GTD.

Invasive hydatidiform mole is a relative rare form of gestational trophoblastic disease (GTD). Most of hydatidiform moles remit after evacuation but some of them have the tendency to invade the myometrium. In some rare cases the trophoblastic tissue can be found in other tissues like lungs, vulva, vagina or broad ligament. The aim of the study was to demonstrate some of clinical, immunohistochemical and DNA analysis findings of a patient with a previous diagnosis of a complete hydatidiform mole.

Base Sequence↗
PubMed2005

[Study of gene differential display of hydatidiform moles].

OBJECTIVE: To screen the specific molecular maker of invasive hydatidiform moles (HM) by differential display analysis. METHODS: For dot hybridization, about 1.0 microg of each cDNA sample of invasive and non-invasive HM were labeled as probes using the Dig DNA labeling and Detection Kit (Boehringer Mannheim). The specific expression fragments of invasive HM recovered from PAGE gel were re-amplified by PCR, and the PCR products were dotted onto nylon membrane and hybridized by two probes of invasive and non-invasive HM cDNA respectively. Some fragments with a strong positive hybridization signal were cloned into the polylinker of lasmid PUC19 and were sequenced. The fragments' sequences were searched for homology in the NCBI data using the BLAST (Database: GenBank Human EST entries; Posted date:Aug 31, 2004; Number of letters in database: 1,697,659,032; Number of sequences in database: 3,677,722). RESULTS: The 20 fragments in 28 bands with specific expression in invasive HM were re-amplified, of which 13 showed positive hybridization signals, and 3 were cloned into the polylinker of lasmid PUC19. A fragment in the 3 was a new expressed sequence tag (EST) and the sequence was submitted to NCBI data (dbEST_Id: 10875704; GenBank_Accn: BM403211). CONCLUSION: There are more differences in gene expression between invasive and non-invasive HMs, and differential display analyses are of a potential significance to early diagnosis of invasive HM.

Adult↗
PubMed1980

Trophoblastic disease: analysis of 342 patients.

The registry for trophoblastic disease in Wakayama, Japan was formed and 342 cases were analyzed. The total number of trophoblastic disease was 342 during 6 years (1972-1977). The number of hydatidiform moles, invasive moles, choriocarcinoma and transitional moles was 278 (81.3%), 28 (8.2%), 18 (5.3%) and 12 (3.5%), respectively. The greatest number of hydatidiform moles occurred in the range 25-29 years inclusive. The percentage of patients with hydatidiform moles over 45 years of age was significantly high. The incidence of malignant complications (invasive moles and choriocarcinoma) of hydatidiform moles was 16.5% in 284 molar pregnancies. The frequency of malignant complications was remarkably high in women over 40 years of age. Thus the epidemiologic study of trophoblastic disease might turn up some important data and the importance should be emphasized.

Adolescent↗
PubMed1976

Hydatidiform mole metastasizing to the lung.

Pulmonary lesions developed in three patients with an invasive hydatidiform mole. At open thoracotomy the modules were found to contain molar tissue. Therapy with twice-weekly methotrexate induced complete clinical and biologic remission of the disease in all three patients.

Adolescent↗
PubMed1978

Selective expression of paternal human major histocompatibility antigens on the surface of hydatidiform mole cells.

The typing of human major histocompatibility antigens (HLA) of two cases of invasive hydatidiform mole showed that the fibroblast-like cells as well as trophoblasts from the mole selectively expressed paternal HLA haplotype specificity but not maternal HLA on the surface. This result was completely in agreement with the notion of androgenetic origin of hydatidiform mole from the aspects of HLA specificity. Immunological implication of this finding and development of chorionic tumor were discussed in the light of fetomaternal relationship and host immune surveillance against the tumor.

Epitopes↗
PubMed1986

Invasive partial mole.

A case of invasive partial hydatidiform mole requiring chemotherapy and hysterectomy in a 30-year-old white woman is presented. This is the first histologically and cytogenetically documented partial mole with persistent elevation of human chorionic gonadotropin (hCG) level and invasion of myometrium. There was no evidence of distant spread.

Adult↗
PubMed1994

[Lung metastasis after pelviscopic salpingectomy in therapy of tubal pregnancy].

UNLABELLED: A 34-year old VI gravida, II para underwent a pelviscopic salpingectomy of the left fallopian tube for treatment of a repeated ectopic pregnancy. Histology revealed an invasive hydatidiform mole. The declining beta-hCG titers after surgery were not further controlled. Seven months later a secondary amenorrhoea occurred again; beta-hCG levels increased steadily. We could not obtain trophoblastic tissue by operative pelvis-copy (excision of the tubal stump on the left side and tubal sterilisation on the right side) nor by curettage of the uterine cave. A lesion of the lung was interpreted as a metastatic lesion following malignant transformation of the invasive hydatidiform mole and disappeared under cytotoxic therapy containing methotrexate with an uneventful follow-up period of now 4 years. RECOMMENDATION: In order not to overlook the presence of persistent trophoblastic tissue and the possible development of a choriocarcinoma, beta-hCG serum titers should be measured until they disappear, following the surgical therapy of an ectopic pregnancy.

Adult↗
PubMed1994

Intrapartum uterine rupture in a primiparous patient previously treated for invasive mole.

BACKGROUND: Intrapartum rupture of the uterus in a primiparous patient is an exceedingly rare event. This case report describes uterine rupture in a woman with previous invasive hydatidiform mole. CASE: A 27-year-old primiparous woman with a history of gestational trophoblastic neoplasia treated successfully with chemotherapy experienced intrapartum uterine rupture with subsequent neonatal death. Magnetic resonance imaging of the uterus had shown evidence of myometrial invasion by the mole. Weakening of the uterine wall secondary to myometrial destruction is believed to have caused the uterine rupture. CONCLUSION: Many women will attempt to conceive following treatment for gestational trophoblastic neoplasia. It is important to determine whether there is any local invasion of the myometrium, as this can affect intrapartum management in subsequent pregnancies.

Adult↗
PubMed1969

Choriocarcinoma after hydatidiform mole. Studies related to effectiveness of follow-up practice after hydatidiform mole.

Chemotherapy, in conjunction with other methods of treatment, was used in 100 patients with invasive hydatidiform mole or choriocarcinoma following mole. When treatment was instituted within two to six months of the antecedent mole serious drug resistance was not encountered, drug toxicity was slight, the duration of treatment was comparatively short, and sustained remissions were obtained in 57 out of 60 patients. When the start of chemotherapy was delayed beyond six months drug resistance occurred in many instances, toxicity was often severe, the duration of treatment was much longer, and sustained remissions were obtained in 22 out of 40 patients.The practice of giving prophylactic chemotherapy to all patients with mole is not established as effective or safe. Differences in the social background to hydatidiform mole in different geographical areas may be such that conclusions based on evidence from one area are not necessarily applicable to another.Careful follow-up after mole remains essential, though present methods often fail to ensure recognition of choriocarcinoma while it is still curable. Standard qualitative and quantitative methods for detecting the continued excretion of chorionic gonadotrophin, though useful, are sometimes too insensitive. It is suggested that to supplement local arrangements some form of centralized or regionalized follow-up service based on notification of patients with hydatidiform mole, and making use of radioimmunoassays for chorionic gonadotrophin, could reduce deaths attributable to late diagnosis.

Adolescent↗
PubMed2002

Current understandings of the molecular genetics of gestational trophoblastic diseases.

Gestational trophoblastic disease (GTD) is a heterogeneous group of diseases characterized by abnormally proliferating trophoblastic tissues. This includes partial and complete hydatidiform moles, invasive mole, choriocarcinoma and placental site trophoblastic tumour. Cytogenetic studies revealed that hydatidiform moles contain either solely (as in complete moles) or an excess (as in partial moles) of paternal contribution to the genome. Genomic imprinting is believed to play a pivotal role in the pathogenesis of hydatidiform moles. However its precise role and mechanism remains poorly understood. Hydatidiform mole carries a potential of malignant transformation. Similar to other human cancers, malignant transformation in gestational trophoblastic tumours is likely a multistep process and involves multiple genetic alterations including activation of oncogenes and inactivation of tumour suppressor genes. In addition, expression of telomerase activity, altered expression of cell--cell adhesion molecules and abnormal expression of matrix metalloproteinases have also been reported in GTD. These represent disruption of the delicate balance and regulation of cellular processes including proliferation, differentiation, apoptosis and invasion. The significance of these alterations in the pathogenesis and malignant transformation of gestational trophoblastic diseases is reviewed in this paper.

Adult↗
PubMedDate not supplied

Expression of nm23-H1 protein in relation to myometrial invasion in complete hydatidiform moles.

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.

Chorionic Gonadotropin, beta Subunit, Human↗