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

Gestational trophoblastic disease comprises a spectrum of interrelated conditions originating from the placenta. Malignant gestational trophoblastic disease refers to lesions that have the potential for local invasion and metastasis. This compromises many histological entities including hydatidiform moles, invasive moles, gestational choriocarcinomas, and placental site trophoblastic tumors. Before the advent of sensitive assays for human chorionic gonadotropin (hCG) and efficacious chemotherapy, the morbidity and mortality from gestational trophoblastic disease were substantial. Currently, with sensitive quantitative assays for beta-hCG and current approaches to chemotherapy, most women with malignant trophoblastic disease can be cured. We present a case of malignant gestational trophobalstic tumor with serum beta-hCG concentration over 1million IU/L that metastaze to the lungs and have a hyperthyroidism, but negative urine hCG testing. We report a case with a brief review of literatures.
Choriocarcinoma ; Chorionic Gonadotropin ; Drug Therapy ; Female ; Gestational Trophoblastic Disease ; Humans ; Hydatidiform Mole, Invasive ; Hyperthyroidism ; Lung ; Mortality ; Neoplasm Metastasis ; Placenta ; Pregnancy ; Trophoblastic Tumor, Placental Site ; 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

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

Gestational trophoblastic disease (GTD) is a condition of uncertain etiology, choriocarcioma, or placental-site hydatidiform moles, invasive moles, choriocarcinoma, and placental-site trophoblastic tumors. It arises from the abnormal proliferation of trophoblastic tissue and spreads beyond the uterus hematogenously. The early diagnosis of GTD is important to ensure timely and successful management and the preservation of fertility. We report the unusual case of a metastatic choriocarcinoma that formed bullae on the lung surface and presented as recurrent pneumothorax in a 38-year-old woman with elevated beta-human chorionic gonadotropin (hCG) levels. She underwent thoracoscopic wedge resection of the involved lung and four subsequent cycles of consolidation chemotherapy. No other evidence of metastatic disease or recurrent pneumothorax was noted during 22 months of follow-up. GTD should be considered in the differential diagnosis of spontaneous pneumothorax in reproductive-age women with an antecedent pregnancy and abnormal beta-hCG levels.
Adult ; Choriocarcinoma* ; Chorionic Gonadotropin ; Consolidation Chemotherapy ; Diagnosis, Differential ; Drug Therapy ; Early Diagnosis ; Female ; Fertility ; Follow-Up Studies ; Gestational Trophoblastic Disease ; Humans ; Hydatidiform Mole, Invasive ; Lung ; Neoplasm Metastasis* ; Pneumothorax* ; Pregnancy ; Trophoblastic Tumor, Placental Site ; Trophoblasts ; Uterus

Epithelioid trophoblastic tumor (ETT) is a very rare variant of gestational trophoblastic disease (GTD) which arises in reproductive age women with prior gestational history. Although abnormal vaginal bleeding is the most common symptom of ETT, there are no reported pathognomonic symptoms of ETT because of its rarity. ETT is similar to placental site trophoblastic tumor in terms of its slow growing characteristic and microscopic findings. Therefore, it could be misdiagnosed as placental site trophoblastic tumor or other types of GTD. Unlike other types of GTD, primary treatment of ETT is surgical resection because of its chemo-resistant nature. Accordingly, immunohistochemical staining is essential for accurate diagnosis and appropriate treatment. Here, we report a case of a 42-year-old hysterectomized woman with pelvic masses who suffered from abdominal pain. Through laparotomy, tumors were resected completely and they were diagnosed as ETT through immunohistochemical stain. This report provides more evidence about its clinical features, diagnosis, and treatment including a brief review of the literature.
Abdominal Pain ; Adult ; Diagnosis ; Female ; Gestational Trophoblastic Disease ; Humans ; Laparotomy ; Trophoblastic Neoplasms* ; Trophoblastic Tumor, Placental Site ; Trophoblasts* ; Uterine Hemorrhage

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

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

Gestational trophoblastic neoplasia (GTN) represents the malignant end of the gestational trophoblastic disease spectrum and includes the more common types, invasive mole (IM) and choriocarcinoma (CC) and the rare types, placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT). This is a case of a 42-year-old, G2P2 (2002) patient who complained of left lower quadrant pain and a 1 year history of amenorrhea. Urine pregnancy test done just prior to the surgery revealed positive result. Pre-operative diagnosis was abdominopelvic mass mass probably Sarcoma, ovarian new growth probably benign, right. Patient underwent exploratory laparotomy, adhesiolysis, bilateral internal iliac artery ligation, total hysterectomy with bilateral salpingo-oophorectomy, targeted biopsy, appendectomy, JP drain insertion under epidural anesthesia. Final histopathologic and immunohistochemical diagnosis is Epithelioid Trophoblastic Tumor. Differential diagnoses, diagnostics, and therapeutic options are presented, with focus on the description of sonographic features.
Trophoblastic Tumor, Placental Site ; Gestational Trophoblastic Disease

Placental site trophoblastic tumor (PSTT) with uterine arteriovenous malformation (AVM) is a rare and potentially catastrophic occurrence. A high index of suspicion and immunohistochemistry secured the diagnosis. The use of appropriate imaging modalities led to the identification of the extent of the disease. Sequential planned management from neoadjuvant intensive chemotherapy, bilateral uterine artery embolization, and laparotomy, and coordinated among different medical disciplines resulted to a successful definitive treatment. Due to its relatively chemoresistant nature, hysterectomy is the mainstay of treatment. Adjuvant platinum-based intensive chemotherapy has been shown to improve overall survival in patients with metastatic disease and those with poor prognostic factors. This case of PSTT with a typical clinical profile was noteworthy due to the development of a significant AVM, a rare complication of PSTT. This case report included a review of treatment experiences as well as peculiarities that set PSTT apart from the more common gestational trophoblastic diseases.
Gestational Trophoblastic Disease ; Trophoblastic Tumor, Placental Site