LINE-1 Methylation Patterns as a Predictor of Postmolar Gestational Trophoblastic Neoplasia

Objective. To study the potential of long interspersed element-1 (LINE-1) methylation change in the prediction of postmolar gestational trophoblastic neoplasia (GTN).Methods. The LINE-1 methylation pattern from first trimester placenta, hydatidiform mole, and malignant trophoblast specimens were compared. Then, hydatidiform mole patients from 11999 to 2010 were classified into the following 2 groups: a remission group and a group that developed postmolar GTN. Specimens were prepared for a methylation study. The methylation levels and percentages of LINE-1 loci were evaluated for their sensitivity, specificity, and accuracy for the prediction of postmolar GTN.Results. First, 12 placentas, 38 moles, and 19 malignant trophoblast specimens were compared. The hydatidiform mole group had the highest LINE-1 methylation level (p= 0.003) and theuCuC of LINE-1 increased in the malignant trophoblast group (p≤ 0.001). One hundred forty-five hydatidiform mole patients were classified as 103 remission and 42 postmolar GTN patients. The %mCuC and %uCmC of LINE-1 showed the lowestpvalue for distinguishing between the two groups (p< 0.001). The combination of the pretreatmentβ-hCG level (≥100,000 mIU/mL) with the %mCuC and %uCmC, sensitivity, specificity, PPV, NPV, and accuracy modified the levels to 60.0%, 92.2%, 77.4%, 83.8%, and 82.3%, respectively.Conclusions. A reduction in the partial methylation of LINE-1 occurs early before the clinical appearance of malignant transformation. The %mCuC and %uCmC of LINE-1s may be promising markers for monitoring hydatidiform moles before progression to GTN.

Malignant disease in pregnancy

Cancer in pregnancy is rare, affecting less than 1 in 1000 live births. It may be specific to pregnancy (gestational trophoblastic disease) or incidental to it, the less infrequent conditions being melanoma, lymphoma, and cervical malignancy. Gestational trophoblastic disease—a group of conditions that arise in the fetal chorion during various types of pregnancy: histologically they are categorized as (1) partial or complete hydatidiform mole, (2) gestational choriocarcinoma, or (3) placental site trophoblastic tumour. The most common of these conditions is molar pregnancy, when villi are present in association with malignant trophoblast in gestational choriocarcinoma....

Choriocarcinoma – postdisease ultrasonographic findings

This is a case report of consequences that malignant gestational trophoblastic disease (GTD) can cause on reproductive health protruding into uterine wall and damaging uterine tissue. Transvaginal Doppler ultrasound examination can be of great value in detecting molar tissue, protrusion of malignant trophoblast in uterine wall, and neovasularization in malignant tissue. It is expected to measure a low resistance index in a field of neovascularization, because neovascularization in malignancy is not rare and those vessels do not have muscular stratum. This case is an example of possible irreversible serious and large damages that can be seen after successful treatment of GTD. They are warning on possible high degree of malignancy in GTD as well as on possible serious impact on reproductive health.

Human placental cytotrophoblasts produce the immunosuppressive cytokine interleukin 10.

The mechanism by which the mammalian mother accepts the implanting fetus as an allograft remains unexplained, but is likely to be the result of a combination of factors. Mononuclear cytotrophoblasts, the specialized fetal cells of the placenta that invade the uterus, play an important role. These cells express HLA-G, an unusual major histocompatibility complex class I-B molecule, and secrete cytokines and pregnancy-specific proteins that can regulate immune function. We investigated whether cytotrophoblasts secrete interleukin 10 (IL-10), a cytokine that potently inhibits alloresponses in mixed lymphocyte reactions. Cytotrophoblasts from all stages of pregnancy produced IL-10 in vitro, but neither placental fibroblasts nor choriocarcinoma (malignant trophoblast) cell lines did so. Spontaneous IL-10 production averaged 650, 853, and 992 pg/10(6) cells in the first, second, and third trimesters of pregnancy, respectively. IL-10 secretion dropped approximately 10-fold after the first 24 h of culture, and was paralleled by a decrease in messenger RNA. IL-10 messenger RNA was detected in biopsies of the placenta and the portion of the uterus that contains invasive cytotrophoblasts, suggesting that this cytokine is also produced in vivo. IL-10 secreted by cytotrophoblasts in vitro is bioactive, as determined by its ability to suppress interferon gamma production in an allogeneic mixed lymphocyte reaction. We conclude that human cytotrophoblast IL-10 may be an important factor that contributes to maternal tolerance of the allogeneic fetus.

Sad Fetus Syndrome - Gestational Trophoblastic Disease Concurrent with a Living Fetus or Fetuses

The term gestational trophoblastic disease is used to indicate a group of both benign and malignant trophoblast, including molar degeneration of villi, hydatid mole, invasive mole and choriocarcinoma.This study shows a new classification of trophoblastic disease existing with a living fetus or fetuses. Benign hydatid mole is the initial stage of the disease continuum, whereas highly malignant choriocarcinoma is the final stage of this spectrum.