The purpose of this study was to evaluate the significance of telomerase activity in gestational trophoblastic disease and the association of telomerase activity in complete hydatidiform mole and subsequent development of persistent gestational trophoblastic tumor. By using the standard telomerase repeat assay, we examined telomerase activity in 2 normal placentas, 31 complete hydatidiform moles, 7 invasive moles, 5 choriocarcinoma tissues and choriocarcinoma cell line (JEG-3). Telomerase activity was detected in 13 of 15 (86.7%) complete hydatidiform mole patients who eventually had chemotherapy for the treatment of persistent gestational trophoblastic tumor. All of the 9 patients with metastatic disease (FIGO Stage III) had telomerase activity in their initial molar tissue. In contrast, telomerase activity was evident in only two of 16 (12.5%) complete hydatidiform mole patients with spontaneous remission. While telomerase activity was not detected in normal placentas, high level of telomerase activity was detected in all of 7 invasive moles, 5 choriocarcinoma tissues and choriocarcinoma cell line (JEG-3). The presence of telomerase activity in a complete hydatidiform mole is associated with the development of persistent gestational trophoblastic tumor, such as invasive mole and choriocarcinoma.
Cell Line ; Choriocarcinoma ; Drug Therapy ; Female ; Gestational Trophoblastic Disease* ; Humans ; Hydatidiform Mole ; Hydatidiform Mole, Invasive ; Molar ; Placenta ; Pregnancy ; Remission, Spontaneous ; Telomerase* ; Telomere ; Trophoblastic Neoplasms

Mutations in the tumor suppressor p53 gene are the most frequently observed genetic lesions in human cancers. It seems that wild type p53 does significant role on growth and differentiation of normal cells, Mutations and allelic loss of the p53 gene are thought to be a cause of tumor development and to be correlated with the prognostic factors in various human cancers such as breast, ovary and lung cancer. Mutant p53 proteins have a prolonged half-life and can be detected by immunohistochemistry. In case of GTD(gestational trophoblastic disease), although the mutation of p53 gene mutation was revealed to be very rare, the overexpression of p53 in immunohistochemical staining has been reported in wide range of discrepancy and its role or prognostic significance in GTD is uncertain. This study is performed to define the status of p53 overexpression in GTD and to evaluate the correlations between p53 overexpression and prognostic factors of GTD. THE RESULTS WERE AS FOLLOWS: 1. p53 overexpression was detected in none of normal placental tissue, in 58.3%(14/24) of hydatidiform mole, in 15%(6/8) of invasive mole, in 75%(3/4) of choriocarcinoma, and in 100%(1/1) of placental site trophoblastic tumor, and showed significant difference between normal placenta and GTD. We could not find any difference of the p53 overexpression between benign group(H-mole) of GTD and malignant one(invasive mole, choriocarcinoma, and placental site trophoblastic tumor) 2. In H-mole, low-risk group showed significantly higher prevalence of p53 overexpression than high-risk group did. In malignant group, there is no difference in the prevalence of p53 overexpression between early(FIGO stage I) and late(II- IV)stage-diseases, but the prevalence of p53 overexpression of low-risk group is slightly higher than that of high-risk group although we failed to find statistical significance. In conclusion, the high prevalence of p53 overexpression in GTD suggests that p53 may have a certain role in the pathogenesis of GTD or at least represent generalized DNA damage or genetic instability of GTD. And the higher prevalence of p53 overexpression in low-risk group suggests that accumulation of wild-type p53 may be related with favorable prognosis in GTD.
Breast ; Choriocarcinoma ; DNA Damage ; Female ; Genes, p53 ; Gestational Trophoblastic Disease* ; Half-Life ; Humans* ; Hydatidiform Mole ; Hydatidiform Mole, Invasive ; Immunohistochemistry ; Loss of Heterozygosity ; Lung Neoplasms ; Ovary ; Placenta* ; Pregnancy ; Prevalence ; Prognosis ; Trophoblastic Tumor, Placental Site ; Trophoblasts

Background: Administration of chemotherapy to prevent postmolar gestational trophoblastic neoplasia was first implemented in the 1960’s. However, its use has remained controversial. Objectives: This study aimed to describe the effect of chemoprophylaxis in preventing progression of hydatidiform mole to gestational trophoblastic neoplasia among patients managed in a tertiary hospital in Davao City from 2011 to 2015. Materials & Method: This retrospective cross-sectional study evaluated 123 cases of hydatidiform mole who were managed at a tertiary hospital in Davao City from the years 2011 to 2015. The patients’ charts were retrieved to get the clinicodemographic profile, progression to gestational trophoblastic neoplasia, and occurrence of adverse effects secondary to chemoprophylaxis. Patients with rising or plateauing beta human chorionic gonadotropin titer were identified within the 3-year period from molar evacuation. Collected data were analyzed using frequency and percentage distribution. Results: The mean age of the patients was 30.5 years, 24% of whom were noted in women more than 40 years of age. The average age of gestation on admission was 14.89 weeks. All patients had a histopathologic diagnosis of complete mole and at least one risk factor for developing postmolar gestational trophoblastic neoplasia. Patients did not experience any significant side effect to chemoprophylaxis. None of the patients developed gestational trophoblastic neoplasia within the 3-year period of monitoring. Conclusion The administration of chemoprophylaxis to patients diagnosed with hydatidiform mole may be effective against the development of postmolar gestational trophoblastic neoplasia.
Pregnancy ; Female ; Gestational Trophoblastic Disease ; Hydatidiform Mole ; Neoplasms ; Chemoprevention

Persistent tumor, usually non-metastatic, develops in approximately 4% of patients with a partial mole, and chemotherapy is required to achieve remission. Following evacuation of hydatidiform mole, careful hCG monitoring is mandatory since it is the most reliable and sensitive method for the early detection of gestational trophoblastic disease. In carefully selected patients in whom the risk of developing gestational trophoblastic disease is significant or when the availability of hCG testing is suboptimal, chemoprophylaxis has been shown to decrease the risk of gestational trophoblastic tumor. We report here a case of patient, 23- year-old woman who experienced unusual course after the evacuation of a partial mole and markedly elevated serum beta-hCG levels. The patient developed persistent metastatic gestational trophoblastic disease and was successfully treated with 3 courses of EMA-CO.
Chemoprevention ; Drug Therapy ; Female ; Gestational Trophoblastic Disease* ; Humans ; Hydatidiform Mole* ; Pregnancy ; Trophoblastic Neoplasms

OBJECTIVETo explore the role of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of MMP-2 (TIMP-2) in the pathogenesis, development and prognosis of gestational trophoblastic disease (GTD).

METHODSIn situ hybridization and immunohistochemistry were utilized for MMP-2/TIMP-2 mRNA and protein detection in normal chorion of women with early gestation, hydatidiform mole, invasive mole, or choricarcinoma.

RESULTSThe results revealed that specific staining for mRNA and protein of MMP-2 and the expression of TIMP-2 was reduced in normal chorion of early gestation. In GTD ranging from hydatidiform mole, invasive mole to choricarcinoma, MMP-2 expression tended to increase while TIMP-2 expression underwent an invert change. The positivity rate of MMP-2 and TIMP-2 in gestational trophoblastic tumor group was higher than that of the normal chorion of early gestation group and hydatiform mole group (P<0.05 and P<0.001, respectively).

CONCLUSIONA disrupted balance between the activation and inhibition of MMP-2 plays a critical role in the pathogenesis, progression and metastasis of GTD.

Choriocarcinoma ; genetics ; metabolism ; Female ; Gestational Trophoblastic Disease ; genetics ; metabolism ; Humans ; Hydatidiform Mole ; genetics ; metabolism ; Hydatidiform Mole, Invasive ; genetics ; metabolism ; Immunohistochemistry ; In Situ Hybridization ; Matrix Metalloproteinase 2 ; biosynthesis ; genetics ; Pregnancy ; Tissue Inhibitor of Metalloproteinase-2 ; biosynthesis ; genetics ; Trophoblasts ; metabolism ; Uterine Neoplasms ; genetics ; metabolism

OBJECTIVE: To evaluate the clinical characteristics and the outcome of the management for gestational trophoblastic disease (GTD) patients diagnosed at our hospital and to report the current situation of GTD in Korea. METHODS: Between January, 1991, and December, 2000, One hundred and eleven women were diagnosed as GTD and managed in our hospital. Patients were classified according to clinical diagnosis and their medical records were investigated. RESULTS: Cases of benign, malignant nonmetastatic, malignant metastatic low risk and malignant metastatic high risk GTDs were 62, 36, 2 and 11 respectively. The mean age (year), gravidity and parity (number) of GTD patients were 33.3+/-9.9 (range: 19-54), 3.2+/-3.0 (range: 0-16) and 1.7+/-1.8 (range: 0-7) overall. About 75% of GTD patients were women in their 20s and 30s, and 85% occurred in patients with parity of 3 or less. The most common prior gestational event was abortion (37.1%) for molar pregnancy and molar pregnancy (61.2%) for persistent gestational trophoblastic tumor (PGTT). The progression rate of molar pregnancies to PGTT was 38.0%. MTX (16.3%) was mainly used as a single agent, and EMACO (28.6%) or MAC (22.4%) were primarily used for multidrug chemotherapy for the treatment of PGTT. In the treatment of PGTT, overall remission rate was 95.9% (n=47/49). CONCLUSION: The trends for GTD in Korea revealed significant changes, not only a decrease in the incidence of GTD, but also an improvement in the outcome of the management. There is a necessity of further community-based surveys for GTD.
Diagnosis ; Drug Therapy ; Female ; Gestational Trophoblastic Disease* ; Gravidity ; Humans ; Hydatidiform Mole ; Incidence ; Korea ; Medical Records ; Parity ; Pregnancy ; Trophoblastic Neoplasms

OBJECTIVE: The purpose of this study is to reevaluate the prognostic factors by investigating the clinical and biological parameters concerned malignant gestational trophoblastic tumor in patients with hydatidiform mole. METHODS: From March 1995 to February 2000, 41 patients admitted to department of the Obstetrics and Gynecology, Yonsei University College of Medicine who were diagnosed with pathologically-proven gestational trophoblastic disease were selected. Parameters such as age, gravida, parity, presence of theca lutein cyst, ratio of uterine size to gestational age, hCG level, DNA ploidy, S-phase fraction were compared between malignant gestational trophoblastic tumor group and spontaneous remission group. RESULTS: Considering the clinical prognostic factors, the patients were divided into two age groups; the first group consisted of those older than 40 years of age and the second control group consisted of those under 40. The number of patients older than 40 in the spontaneous remission group and malignant gestational trophoblastic tumor group were 4(15.4%) and 7(46.7%), respectively, showing a significantly higher number in the group over 40years. Other parameters such as gravida, parity, presence of theca lutein cyst, ratio of uterine size to gestational age, hCG level, DNA ploidy, S-phase fraction showed no statistically significant difference between the two groups. CONCLUSION: The progression rate from hydatidiform mole to malignant gestational trophoblastic tumor was significantly higher in patients over 40 years of age. Therefore, more aggressive therapeutic approach should be considered in such patients.
DNA ; Female ; Gestational Age ; Gestational Trophoblastic Disease ; Gynecology ; Humans ; Hydatidiform Mole* ; Lutein ; Obstetrics ; Parity ; Ploidies ; Pregnancy ; Remission, Spontaneous ; Trophoblastic Neoplasms* ; Trophoblasts*

PURPOSE: p53 and bcl-2 expressions are known as important cell survival factors and their levels of expression are related with patients prognosis in various human malignancies. But there are few data about p53 and bcl-2 expression and their role in the genesis of gestational trophoblastic disease (GTD). The aims of this study are to describe p53 and bcl-2 expression in normal trophoblast and hydatidifonn mole (HM), and to identify the role of p53 and bcl-2 in the genesis of gestational trophoblastic tumor (GlTI from HM. MATERIALS AND METHODS: Paraffin-embedded tissue sections from 32 cases of HM and 9 cases of normal early pregnancy placentas were obtained. Of 32 HM patients, 15 cases were cured after molar evacuation (group A), and 17 cases progressed to GT1' (group B). p53 and bcl-2 immunohistochemical stainings were done and their reactivity were graded. The positive rates of p53 and bcl-2 overexpression among normal placenta, group A, and group B were compared and analyzed. RESULTS: p53 mutant gene overexpression was more frequently detected in HM (68%) than in normal placentas (22%)(p<0.05). bcl-2 was overexpressed in 31% of HM and 11% of normal placenta, but the difference was statistically insignificant (P > 0.05). The difference in bcl-2 and p53 expression between group A and group B was not observed (P>0.05). There was no inverse relationship between p53 and bcl-2 expression in group A, and group B (P>0.05). CONCLUSIONS: p53 gene mutation may play a mle in the process of HM development, but p53 and bcl-2 were not associated with the genesis of GTI' from H-mole. More studies are needed to identify the molecular process in the progression of the GTD.
Cell Survival ; Female ; Genes, bcl-2* ; Genes, p53 ; Gestational Trophoblastic Disease ; Humans ; Hydatidiform Mole ; Molar ; Placenta ; Pregnancy ; Prognosis ; Trophoblastic Neoplasms ; Trophoblasts*

Epithelioid trophoblastic tumor is a rare type of gestational trophoblastic disease that is distinct from placental site trophoblastic tumor and choriocarcinoma, and epithelioid trophoblastic tumor has features resembling a carcinoma. We report here on an epithelioid trophoblastic tumor that was discovered as a solitary pulmonary nodule in the lung of a 50-year-old woman. The patient had suffered from a hydatidiform mole 20 years previously. Wedge resection of the lung was done and this showed a 1.9x1.5 cm sized, relatively well defined mass composed of mononuclear tumor cells admixed with hyaline-like material and necrosis. The tumor cells were positive for EMA, Cam5.2, alpha-inhibin, PLAP and hCG. After consulting the gynecologic department, a 7.5x6.5 cm sized mass was discovered in the uterine fundus. Hysterectomy was then done. The tumor cells were same to those of the lung mass. The lung mass is considered to be metastasis from the epithelioid trophoblastic tumor of the uterus. She has been an uneventful clinical course for three years.
Biomarkers ; Choriocarcinoma ; Female ; Gestational Trophoblastic Disease ; Humans ; Hydatidiform Mole ; Hysterectomy ; Inhibins ; Keratins ; Lung ; Middle Aged ; Necrosis ; Neoplasm Metastasis ; Pregnancy ; Solitary Pulmonary Nodule ; Trophoblastic Neoplasms ; Trophoblastic Tumor, Placental Site ; Trophoblasts ; Uterus

This study is designed to evaluate the clinical characteristics and the outcomes of the management of gestational trophoblastic disease diagnosed at our hospital. With a retrospective review of hospital record from 1989 to 1998, we analysed 54 cases of gestational trophoblastic disease by the clinical characteristics and the outcomes of management. The results are as follows 1. The incidence of the gestational trophoblastic disease compared with delivery is one per 341 deliveries and is decreasing with time(from one per 252 deliveries at 1989 to one per 694 deliveries at 1998). 2. The most frequent age is 20-29 years old(61,1%). 3, The most frequent gravity and parity is 0-2 times(68.5%) and 0-1 time(79.6%) respectively. 4. The symptoms and signs are amenorrhea(94.4%), vaginal bleeding(74,1%), abdominal pain( 33.3%), hyperemesis gravidarum(25.9%), excessive uterine enlargement(24.1%), anemia(18.5%), hyperthyroidism(7.4%), theca lutein ovarian cyst(3.7%), and preeclampsia (1.9%). 5. We divided the patients by the uterine size for gestational age; large for date 50%, normal for date 44.4%, and small for date 5.6%. 6. The antecedent pregnancies of patients with persistent gestational trophoblastic tumor are hydatidiform mole 87.5%, abortion 12.5% in middle risk group and hydatidiform mole 66.7%, term pregnancy 22.2%, abortion 11,1% in high risk group. 7. We divided the patients with persistent gestational trophoblastic tumor by the FIGO staging system; stage I 70.6%, stage II 5.9%, stage III 11.8%, stage IV 11,8%. 8. The regimens of treatment are consisted of D & E only(59.3%), D & E with prophylactic chemotherapy(9.3%), D & E with chemotherapy(25.9%), and D & E with chemotherapy and hysterectomy(5.6%). Complete remissions are shown in 100% of D & E only and D & E with prophylactic chemotherapy, in 85.7% of D & E with chemotherapy, and in 33.3% of D & E with chemotherapy and hysterectomy. Dividing the patients with persistent gestational trophoblastic tumor by the WHO prognostic scoring system, complete remissions are shown in 75% of middle risk group and in 77.8% of high risk group. 9. The duration of chemotherapy for complete remission is 2.5 cycles & 77.5 days in middle risk group and 4 cycles & 130.1 days in high risk group. 10. The subsequent pregnancies after complete remission of gestational trophoblastic disease are term delivery 81%, spontaneous abortion 9.5%, induced abortion 4.8%, and preterm delivery 4.8%.
Abortion, Induced ; Abortion, Spontaneous ; Drug Therapy ; Female ; Gestational Age ; Gestational Trophoblastic Disease* ; Gravitation ; Hospital Records ; Humans ; Hydatidiform Mole ; Hysterectomy ; Incidence ; Lutein ; Parity ; Pre-Eclampsia ; Pregnancy ; Retrospective Studies ; Trophoblastic Neoplasms