NCI CANCERLIT^® Search: Gestational Trophoblastic Neoplasms - September 2001

Last Modified: November 1, 2001

Expression of adrenomedullin by human placental cytotrophoblasts and choriocarcinoma JAr cells.
Weekly intravenous methotrexate with folinic acid for nonmetastatic gestational trophoblastic neoplasia.
A study of human leukocyte antigen G expression in hydatidiform moles.
Choriocarcinoma and partial hydatidiform moles.
When trophoblastic disease is suspected.
Placental site trophoblastic tumor--past as prologue.
Placental site trophoblastic tumor: a 17-year experience at the New England Trophoblastic Disease Center.
Upregulation of neutral endopeptidase expression and enzymatic activity during the differentiation of human choriocarcinoma cells.
[Pregnancy of patients conceived within one year after chemotherapy for gestational trophoblastic tumor]

CancerMail from the National Cancer Institute

1
UI - 21394128
AU - Moriyama T; Otani T; Maruo T
TI - Expression of adrenomedullin by human placental cytotrophoblasts and choriocarcinoma JAr cells.
SO - J Clin Endocrinol Metab 2001 Aug;86(8):3958-61
AD - Department of Obstetrics and Gynecology, Kobe University School of Medicine, Kobe 650-0017, Japan.
Adrenomedullin is a multifunctional peptide expressed in a variety of tissues. This study was conducted to investigate the expression of adrenomedullin and its mRNA by human trophoblasts and the possible existence of adrenomedullin receptor in those cells. Human placentas in all three trimesters were obtained from patients undergoing therapeutic abortions and deliveries. Total RNA was extracted from placental trophoblastic tissues and JAr choriocarcinoma cells, and the expression of adrenomedullin mRNA was determined by RT-PCR. Immunohistochemical analysis was performed by the avidin/biotin immunoperoxidase method using a specific antibody to adrenomedullin. The secretion of adrenomedullin by JAr cells cultured in medium containing [35S]cysteine-[35S]methionine was determined by immunoprecipitation followed by PAGE. The presence of adrenomedullin receptor in JAr cells was examined using a binding assay with [125I]rat adrenomedullin. Adrenomedullin mRNA was expressed by human placental trophoblastic tissues in all three trimesters and by JAr cells. Immunohistochemical analysis revealed that adrenomedullin is expressed by cytotrophoblasts in placentas in all three trimesters, but not by syncytiotrophoblasts. The expression of adrenomedullin in the cytotrophoblast was most abundant in first trimester placenta and became less abundant during the course of pregnancy. JAr cells synthesized and secreted immunoreactive adrenomedullin. Binding assay with [125I]rat adrenomedullin demonstrated specific binding of adrenomedullin to JAr cells, indicating the existence of a specific receptor for adrenomedullin in trophoblastic cells. Adrenomedullin is transcribed and secreted by cytotrophoblastic cells that possess adrenomedullin receptor. Adrenomedullin may play a potential role as an autocrine/paracrine factor in the growth of cytotrophoblasts, especially in early gestation.

2
UI - 21423713
AU - Kwon JS; Elit L; Mazurka J; Moens F; Schmuck ML
TI - Weekly intravenous methotrexate with folinic acid for nonmetastatic gestational trophoblastic neoplasia.
SO - Gynecol Oncol 2001 Aug;82(2):367-70
AD - Division of Gynecologic Oncology, University of Toronto, Toronto, Canada.
OBJECTIVE: The objective of this study was to determine the complete response rate to weekly intravenous methotrexate at 100 mg/m(2) with folinic acid for patients with nonmetastatic gestational trophoblastic neoplasia. METHODS: From 1988 to 1999, 22 women with nonmetastatic gestational trophoblastic neoplasia were treated with weekly intravenous methotrexate with folinic acid at the Hamilton Regional Cancer Centre. Complete response was defined as the attainment of a serum beta-hCG level <5 IU/L for 3 consecutive weeks. Toxicity was graded according to the National Cancer Institute of Canada-Clinical Trials Group criteria for chemotherapy toxicity. RESULTS: There were 10 women who achieved complete response with weekly intravenous methotrexate alone (45.5%). Of the 12 who did not achieve complete response with methotrexate, 10 received actinomycin D and 2 received EMA as second-line chemotherapy. Patients successfully treated with methotrexate required a median of 6.5 cycles (including 2 cycles for consolidation) to achieve complete response. The only significant prognostic factor for failure with methotrexate was pretreatment beta-hCG (P = 0.01). CONCLUSIONS: Only a select group of patients with low pretreatment beta-hCG titers would be expected to achieve complete response with this regimen. Large randomized studies are required to determine the optimal treatment for nonmetastatic gestational trophoblastic neoplasia. Copyright 2001 Academic Press.

3
UI - 21409743
AU - Goldman-Wohl D; Ariel I; Greenfield C; Hochner-Celnikier D; Lavy Y; Yagel S
TI - A study of human leukocyte antigen G expression in hydatidiform moles.
SO - Am J Obstet Gynecol 2001 Aug;185(2):476-80
AD - Department of Obstetrics and Gynecology, Hadassah University Hospital, Jerusalem, Israel.
OBJECTIVE: Human leukocyte antigen G (HLA-G) is a nonclassic major histocompatibility gene normally expressed only in extravillous trophoblasts throughout pregnancy. It may be responsible in part for the successful evasion of the hemiallogenic trophoblasts from maternal immune surveillance. We investigated whether HLA-G is expressed in molar pregnancies. STUDY DESIGN: We examined 5 complete hydatidiform mole specimens and 5 partial hydatidiform mole specimens to determine whether HLA-G is expressed by immunohistochemistry and by RNA in situ hybridization analysis. RESULTS: We found that both the protein and RNA of HLA-G is expressed in complete and partial hydatidiform moles. CONCLUSION: HLA-G RNA and protein are expressed in molar pregnancies. HLA-G expression is independent of embryonic development and may therefore be an integral part of placental development. Furthermore, expression of HLA-G in the complete hydatidiform mole, a naturally occurring androgenote, confirms expression of the paternal allele of HLA-G. Imprinting of HLA-G is therefore unlikely to play a role in protecting fetal trophoblasts from maternal immune rejection.

4
UI - 20348852
AU - Seckl MJ; Fisher RA; Salerno G; Rees H; Paradinas FJ; Foskett M; Newlands ES
TI - Choriocarcinoma and partial hydatidiform moles.
SO - Lancet 2000 Jul 1;356(9223):36-9
AD - Department of Medical Oncology, Imperial College, London, UK. m.seckl@ic.ac.uk
BACKGROUND: Partial hydatidiform moles (PMs) rarely require chemotherapy and have never previously been proven to transform into choriocarcinoma, the most malignant form of gestational trophoblastic disease (GTD). Consequently, some have questioned whether women with PMs need human chorionic gonadotropin (hCG) follow-up. Here, we investigate whether PMs can transform into choriocarcinomas. METHODS: Patients with a PM who developed a subsequent choriocarcinoma were identified from our GTD database. The histology of both PM and ensuing choriocarcinoma was reviewed and flow cytometry used to verify the triploid status of the PMs. To determine whether the choriocarcinoma arose from the PM, DNA from the PM and choriocarcinoma in each patient was compared using microsatellite polymorphisms. FINDINGS: Of the 3000 patients with PM, 15 required chemotherapy for persisting GTD. This was identified as choriocarcinoma in three cases. In one patient, the local pathologist could not differentiate between a PM or a hydropic abortion and neither central histological review nor hCG follow-up were obtained. This patient nearly died before the diagnosis of choriocarcinoma was made. Fortunately, the local pathologists correctly diagnosed PM in the two other patients who were then registered for hCG follow-up. Some months later, the hCG was rising and repeat uterine evacuation revealed choriocarcinoma. The PM was confirmed to be triploid in all three cases and genetic analysis showed that the subsequent choriocarcinomas contained identical single maternal and two paternal alleles at several independent loci. INTERPRETATION: Our results show that PMs can transform into choriocarcinoma. All patients with suspected PM should be reviewed centrally and, if confirmed, need hCG follow-up.

5
UI - 20505800
AU - Poller DN
TI - When trophoblastic disease is suspected.
SO - Lancet 2000 Oct 21;356(9239):1443-4

6
UI - 21411770
AU - Shih IM; Kurman RJ
TI - Placental site trophoblastic tumor--past as prologue.
SO - Gynecol Oncol 2001 Sep;82(3):413-4

7
UI - 21411771
AU - Feltmate CM; Genest DR; Wise L; Bernstein MR; Goldstein DP; Berkowitz RS
TI - Placental site trophoblastic tumor: a 17-year experience at the New England Trophoblastic Disease Center.
SO - Gynecol Oncol 2001 Sep;82(3):415-9
AD - Division of Gynecologic Oncology, Brigham and Womens Hospital, Boston, Massachusetts 02115, USA.
OBJECTIVE: We reviewed cases of placental site trophoblastic tumors from the New England Trophoblastic Disease Center (NETDC) database from 1982-1999 in an effort to identify prognostic factors for recurrent disease. METHODS: A chart review was performed utilizing patients identified from the NETDC database. Data obtained included patient age at diagnosis, antecedent pregnancy, duration and extent of disease, presenting symptoms, pre- and posttreatment hCG levels, diagnostic and therapeutic procedures, treatment and outcome of patients. Statistical analysis was performed using Student's t test and chi(2) test when appropriate. RESULTS: Thirteen patients were identified. All ultimately underwent hysterectomy although initial treatment of 1 patient was uterine resection. There were 5 recurrences (43%)--3 among the 9 patients who had no metastases on presentation (33%) and 2 of 3 patients who presented with metastases (66%). The 5 patients who recurred were among 8 who had received peri- or postoperative chemotherapy (62.5%). Treatment of recurrences included continued or alternate chemotherapy, radiotherapy, and/or excision of locally recurrent disease. Follow up time averaged 56.2 months (range 12-182 months). One of the 4 patients receiving chemotherapy < or =1 week after hysterectomy recurred, whereas all 4 patients who received chemotherapy 3 weeks or more after hysterectomy recurred. Uterine tumor volume was significantly greater, 154.1 cm(3), in patients with initial metastases versus 42.3 cm(3) in patients without initial metastases (P = 0.04). Mitotic index (P = 0.04) was significantly increased in patients who developed recurrent disease. CONCLUSION: High mitotic index appears to be an adverse prognostic indicator for recurrence. Hysterectomy remains the mainstay of treatment. Chemotherapy is indicated for patients with metastases and may be indicated when the mitotic index is >5 mitoses/10 HPF. Radiation treatment may play a role in recurrent disease but must be evaluated on a case-by-case basis. Copyright 2001 Academic Press.

8
UI - 21334646
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.

9
UI - 21371105
AU - Zhu L; Yang X; Song H
TI - [Pregnancy of patients conceived within one year after chemotherapy for gestational trophoblastic tumor]
SO - Zhonghua Fu Chan Ke Za Zhi 1999 Oct;34(10):618-20
AD - Peking Union Medical College, Beijing 100730.
OBJECTIVE: To explore the risk of pregnancy in patients conceived within one year after successful chemotherapy for gestational trophoblastic tumor. METHODS: 22 patients conceived within one year after chemotherapy were followed up and analysed about abnormal pregnant result, wastage rate and the time of interval between chemotherapy and pregnancy. RESULTS: Among 22 cases, 9 cases were full term birth, 6 cases were wastage. The wastage rate was 27.3%. The wastage rate of these patients conceived within half a year was higher than one year (P < 0.05). 1 repeated hydatidiform mole and one post term choriocarcinoma occurred in 22 patients. They both were conceived within 5 months after chemotherapy. CONCLUSIONS: Preservation of fertility is feasible in patients suffering from choriocarcimona and invasive mole. But these patients should practise contraception at least half a year after chemotherapy, and it's better to advise patients to take contraception for one year.