OBJECTIVE: To explore the genetic etiology of recurrent hydatidiform mole (RHM) and provide accurate guidance for reproduction. METHODS: Peripheral venous blood samples of the probands with RHM and members from 5 unrelated pedigrees were collected. Genomic DNA was extracted by using routine method, and whole exome sequencing was carried out to detect variants of RHM-associated genes including NLRP7 and KHDC3L. Sanger sequencing and real-time quantitative PCR (RT-qPCR) were used to validate the candidate variants and delineate their parental origin. RESULTS: Homozygous or compound heterozygous variants of the NLRP7 gene were identified in four patients from three pedigrees, which included a homozygous deletion of exon 1 to 4 of NLRP7 in patient P1 and her elder sister, compound heterozygous variants of NLRP7 c.939delG (p.Q314Sfs*6) pat and c.1533delG (p.N512Tfs*4) mat in patient P2, and compound heterozygous variants of NLRP7 c.2389_2390delTC (p.A798Qfs*6) pat and c.2165A>G (p.D722G) mat in patient P4. All variants were interpreted as pathogenic or likely pathogenic according to the American College of Medical and Genomics (ACMG) guidelines. Among these, NLRP7 exons 1 to 4 deletion, c.939delG (p.Q314Sfs*6), c.1533delG (p.N512Tfs*4) and c.2389_2390delTC (p.A798Qfs*6) were unreported previously. CONCLUSION Variants of the NLRP7 gene probably underlay autosomal recessive RHM in the three pedigrees, and definitive molecular diagnosis is beneficial for accurate genetic counseling. Above finding has also enriched the spectrum of the NLRP7 variants underlying RHM.
Adaptor Proteins, Signal Transducing/genetics* ; Aged ; China ; Female ; Homozygote ; Humans ; Hydatidiform Mole/pathology* ; Mutation ; Pedigree ; Pregnancy ; Sequence Deletion

Invasive mole is a benign gestational trophoblastic disease that arises from the myometrial invasion of any gestational event via direct extension through tissue or vascular structures. Invasive mole (and other gestational trophoblastic diseases) may present with life-threatening complications including uterine perforation, excessive bleeding, acute hemoperitoneum, and abdominal pain. We report a case of invasive mole presenting as abdominal distention in a 51-year-old perimenopausal woman (gravida 12, para 12, abortion 0). The patient was admitted to the gynecology clinic with a giant uterine mass filling the pelvic and abdominal cavity. To our knowledge, this is the first case in the literature of a gestational trophoblastic neoplasia presenting with uterine mass of 28 weeks' gestational size in this age group. Interestingly, complications such as uterine rupture or invasion of the adjacent structures (such as parametrial tissues or blood vessels) had not developed in our patient despite the considerable enlargement of the uterus.
Abdominal Cavity ; Abdominal Pain ; Female ; Gestational Trophoblastic Disease ; Gynecology ; Hemoperitoneum ; Hemorrhage ; Humans ; Hydatidiform Mole, Invasive* ; Hysterectomy ; Middle Aged ; Pathology* ; Pregnancy ; Trophoblasts ; Uterine Perforation ; Uterine Rupture ; Uterus

Gestational trophoblastic tumors (GTTs) are malignant lesions that often cause abnormal genital bleeding and may present with hemoptysis, intraperitoneal bleeding or acute neurologic deficits. GTTs are generally highly chemosensitive with more favorable outcomes than other comparable malignancies. Here we report a rare case of invasive mole (FIGO stage IV, WHO score16) presenting with renal subcapsular hematoma due to bleeding renal metastasis. The patient had a pretreatment β-human chorionic gonadotrophin (β-HCG) level of 462 047 mIU/ml and received combined chemotherapy with etoposide, methotrexate, actinomycin-D, cyclophosphamide and vincristine with also adjuvant surgeries including hysterectomy and nephrectomy. The patient recovered well and the tumor has remained in complete remission for one year and a half.
Antineoplastic Combined Chemotherapy Protocols ; Female ; Hemorrhage ; etiology ; Humans ; Hydatidiform Mole, Invasive ; complications ; Kidney ; pathology ; Pregnancy ; Uterine Neoplasms ; complications

OBJECTIVETo explore the role of the hydatidiform mole-related gene F10 in the tumorigenicity of choriocarcinoma cell lines JEG-3 in nude mice.

METHODSChoriocarcinoma JEG-3 cell lines with stable F10 gene over-expression and F10 gene silencing were established using cell transfection and RNA interference techniques, respectively. Thirty SPF nude mice (4-5 weeks old) were equally randomized into F10 over-expression group, control group, and F10 gene-silenced group for subcutaneous injection of 0.2 ml cell suspension (5 × 10⁷ cells) of F10 gene over-expressing JEG-3 cells, non-treated JEG-3 cells, and F10 gene-silenced JEG-3 cells, respectively. The mice were observed and weighed every 3-4 days, and the tumor formation time was recorded to draw the tumor growth curve and calculate the tumor formation rate.

RESULTSThe tumor formation rates were 100% in all the 3 groups. No significant difference was found in the tumor formation time among the F10 over-expression, F10-silenced and control groups (6.2 ± 0.78 vs 7 ± 2.49 vs 6.3 ± 0.67 days; F=0.781, P=0.468). A significantly greater tumor growth rate was noted in the F10 over-expression group compared with the other two groups (P<0.05), and the growth rate was significantly slower in F10-silenced group than in the control group (P<0.05). The subcutaneous tumor weight at 5 weeks after JEG-3 cell injection differed significantly among F10 over-expression, F10-silenced and control groups (571.1 ± 221.10 vs 136.2 ± 66.25 vs 354.5 ± 116.23 mg; F=21.199, P=0.000).

CONCLUSIONF10 gene plays a role in the regulation of choriocarcinoma JEG-3 cell proliferation and might enhance its tumorigenicity in nude mice.

Animals ; Cell Line, Tumor ; Cell Proliferation ; Choriocarcinoma ; pathology ; Female ; Gene Expression ; Gene Expression Regulation, Neoplastic ; Genes, Neoplasm ; Humans ; Hydatidiform Mole ; genetics ; Mice ; Mice, Nude ; Pregnancy ; Transfection ; Uterine Neoplasms ; pathology

OBJECTIVETo investigate the clinical utility of short tandem repeats(STR) genotyping technique for diagnosis of partial hydatidiform moles (PHM).

METHODSTen cases with the original diagnosis of PHM and six cases diagnosed as "favour PHM" or "abnormal villous, PHM not excluded" were selected for the study. The clinical information and follow-up data were reviewed. Histopathologic features were evaluated along with p57 immunohistochemistry. After DNA extraction from each sample, genotyping was performed by AmpFlSTR(®) Identifiler™ PCR kit to amplify 15 STR polymorphism loci plus the amelogenin gender-determining in a single robust PCR.

RESULTSThe age of patients ranged from 18 to 49 years (mean=29 years, median=29 years). Two villous populations (7/16), irregular villous contour (13/16), at least moderate trophoblastic hyperplasia (2/16), cistern formation (8/16), syncytiotrophoblastic knuckles (14/16), trophoblastic pseudoinclusions (6/16) and nucleated fetal red blood cells (8/16) were presented in these cases. Of the cases in the study, STR genotyping identified 4 monospermic complete hydatidiform moles (MCM), 3 dispermic partial hydatidiform moles (DPM) and 9 hydropic abortions (HA). The misdiagnosis rate was 13/16 only relied on morphology evaluation. Immunostaining of p57 showed 3/4 of MCM were focally positive (<5%-20%+), 1/4 of MCM were diffusely positive (70%+), 3/3 of DPM were diffusely positive (≥50%+), 7/9 of HA were diffusely positive (≥50%+), and 2/9 of HA were focally positive (10%+).

CONCLUSIONSCombination of histomorphologic evaluation and p57 immunostaining is insufficient for a definitive diagnosis of PHM. STR genotyping offers an accurate diagnosis of PHM.

Abortion, Spontaneous ; Adolescent ; Adult ; Cyclin-Dependent Kinase Inhibitor p57 ; metabolism ; Female ; Genotype ; Genotyping Techniques ; Humans ; Hydatidiform Mole ; diagnosis ; genetics ; Immunohistochemistry ; Microsatellite Repeats ; Middle Aged ; Polymerase Chain Reaction ; Pregnancy ; Trophoblasts ; pathology ; Uterine Neoplasms ; diagnosis ; genetics ; Young Adult

Adaptor Proteins, Signal Transducing ; genetics ; Animals ; Female ; Fertilization ; Humans ; Hydatidiform Mole ; genetics ; pathology ; Karyotyping ; Male ; Mosaicism ; Mutation ; Pregnancy ; Spermatozoa ; Uterine Neoplasms ; genetics ; pathology

Twin pregnancy with mosaic partial hydatidiform mole (PHM) and survival of two healthy fetuses following in vitro fertilization and embryos transfer (IVF-ET) is a rare situation and is considered a challenge for management. A 32-year-old Chinese woman conceived twin pregnancy following IVF-ET. At 22 weeks' gestation, an additional intrauterine echogenic mass with features of PHM were shown by successive ultrasound examinations. At 35 weeks' gestation, two live male infants and two placentas were delivered by caesarean section (CS). Histologic examination of the abnormal placenta confirmed mosaic PHM. Genetic study showed the abnormal placental mosaicism (expressed in molar-69XXY and normal vili-46XY), co-existing with a hypospadia new-born (46XY) in one amniotic sac. However, the other one was normal. Serial serum β-hCG levels showed a declining trend and serum β-human chorionic gonadotropin (hCG) were undetectable at 6 months after delivery. The case demonstrated that it is possible to prolonged gestation by PHM under close surveillance during the entire pregnancy.
Adult ; Female ; Fertilization in Vitro ; Humans ; Hydatidiform Mole ; genetics ; Infant, Newborn ; Male ; Mosaicism ; Placenta ; metabolism ; pathology ; Pregnancy ; Pregnancy, Twin ; genetics

OBJECTIVETo investigate the role of p57 and p53 immunohistochemistry in the differential diagnosis of hydropic abortion, partial hydatidiform mole and complete hydatidiform mole.

METHODSImmunohistochemical stains (EnVision method) for p57 and p53 were performed in tissue samples of normal placenta chorionic villi (n=10), abortion chorionic villi (n=12), partial hydatidiform (n=23) and complete hydatidiform moles (n=20).

RESULTSThe expression of p57 was predominantly localized in the nuclei of villous cytotrophoblasts and stromal cells. The positive rates of p57 in normal placenta, hydropic abortion and partial hydatidiform mole were 10/10, 12/12, and 100% (23/23), respectively, with no significant difference among the groups (P>0.05). However, none of the complete hydatidiform moles analyzed exhibited p57 positivity in cytotrophoblasts and stromal cells. There was a significant difference between partial and complete hydatidiform moles (P<0.05). The expression of p53 was observed in the nuclei of cytotrophoblastic cells and intermediate trophoblasts. No p53 expression was seen in normal placenta and only 1 of 12 hydropic abortion showed p53 positivity. The positive rates of p53 expression in partial and complete hydatidiform mole were 60.9% (14/23) and 85.0% (17/20) respectively. It was significantly higher in partial hydatidiform mole than that in hydropic abortion. A significant difference was also found between partial and complete hydatidiform moles (P<0.05).

CONCLUSIONSOur findings confirm that p57 immunohistochemistry assists the differential diagnosis of complete hydatidiform mole from partial hydatidiform mole. Expression of p53 may be helpful in distinguishing partial hydatidiform mole from hydropic abortion.

Abortion, Spontaneous ; diagnosis ; metabolism ; pathology ; Cyclin-Dependent Kinase Inhibitor p57 ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Hydatidiform Mole ; diagnosis ; metabolism ; pathology ; Immunohistochemistry ; Pregnancy ; Stromal Cells ; metabolism ; Trophoblasts ; metabolism ; Tumor Suppressor Protein p53 ; metabolism ; Uterine Neoplasms ; diagnosis ; metabolism ; pathology

Abortion, Induced ; Adult ; Female ; Fetus ; embryology ; Humans ; Hydatidiform Mole ; pathology ; Pregnancy ; Pregnancy Complications, Neoplastic ; pathology ; Pregnancy, Twin ; Uterine Neoplasms ; pathology

OBJECTIVETo study the function of F10 gene, a novel hydaditiform mole-related gene.

METHODSA549 cell line was transfected with the F10 gene of forward or reverse sequence or with the empty vector, respectively. The cellular mRNA was extracted after 24 h of transfection to screen for the differentially expressed genes among the 3 transfected and the control cells using differential display-polymerase chain reaction (ddPCR).

RESULTSThe bands representing differentially expressed genes were amplified from the cells, and the products were linked to T-Vector for sequence analysis. Several genes were screened by Blasting and their expressions were confirmed by fluorescent quantitative PCR.

CONCLUSIONF10 gene is functionally related to cell proliferation and apoptosis.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Epithelial Cells ; metabolism ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Hydatidiform Mole ; genetics ; Hydatidiform Mole, Invasive ; genetics ; Lung Neoplasms ; genetics ; pathology ; Oncogenes ; genetics ; Pregnancy ; Transfection ; Uterine Neoplasms ; genetics