Development Of Persistent Trophoblastic Disease Research Articles

The Contribution of QF-PCR and Pathology Studies in the Diagnosis of Diandric Triploidy/Partial Mole.

Objective: the aim of our study was to assess the contribution of quantitative fluorescent polymerase chain reaction (QF-PCR) and pathology studies in the diagnosis of diandric triploidies/partial hydatidiform moles. Methods: this study included all fet al triploidies diagnosed by QF-PCR in chorionic villi or amniotic fluid in the 2 centers of BCNatal in which a maternal saliva sample was used to establish its parental origin. Pathology studies were performed in products of conception and concordance between a partial hydatidiform mole diagnosis and the finding of a diandric triploidy was assessed. Results: among 46 fetal triploidies, found in 13 ongoing pregnancies and in 33 miscarriages, there were 26 (56%) diandric triploidies. Concordant molecular (diandric triploidy) and pathology results (partial mole) were achieved in 14 cases (54%), while in 6 cases (23%) pathology studies were normal, and in the remaining 6 cases (23%) pathology studies could not be performed because miscarriage was managed medically. Conclusions: diandric triploidy is associated with partial hydatidiform mole and its diagnosis is crucial to prevent the development of persistent trophoblastic disease. QF-PCR analysis in chorionic villi or amniotic fluid provides a more accurate diagnosis of the parental origin of triploidy than the classical pathology studies.

Medical termination of a partial hydatidiform mole and coexisting fetus during the second trimester: A case report.

Partial hydatidiform mole and coexisting fetus (PHMCF) is a rare condition that presents a dilemma for physicians and the parents of the fetus, particularly when PHMCF is detected during the second trimester of pregnancy. The present study reports a case of PHMCF terminated by induction of labor via administration of Rivanol at 17 weeks. Follow-up measurements of serum β-human chorionic gonadotropin (β-HCG) levels, as well as imaging studies, indicated the presence of persistent trophoblastic disease (PTD) and lung metastases. The patient was therefore admitted for three courses of chemotherapy. Subsequently, the metastases receded and β-HCG levels decreased to within the normal range. The patient demonstrated no disease recurrence for 1 year. Following a review of the relevant literature, to the best of our knowledge, all PHMCF cases terminated by medical induction of labor during the second trimester resulted in the development of PTD and lung metastases. However, three cases of PHMCF that were terminated by caesarean section during the third trimester did not develop PTD or metastases. The present study therefore hypothesized that medical termination may not be a safe therapeutic strategy for the treatment of PHMCF during the second trimester, and that pregnancy should be allowed to continue empirically.

Pre-evacuation hCG glycoforms in uneventful complete hydatidiform mole and persistent trophoblastic disease

Objective To investigate whether the glycoform distribution patterns of human chorionic gonadotropin (hCG) obtained by chromatofocusing in pre-evacuation serum are different for patients who will eventually develop into persistent trophoblastic disease in case of complete hydatidiform mole pregnancy as compared to those patients for whom trophoblastic tissue will regress uneventfully. Methods Pre-evacuation blood samples were collected from women with complete hydatidiform mole with uneventful spontaneous regression after molar evacuation ( n = 32), from women with complete hydatidiform mole who developed persistent trophoblastic disease after evacuation of their mole ( n = 28) and, as a control group, from women during the first trimester of normal pregnancy ( n = 22). The serum specimens were subjected to chromatofocusing, and hCG was determined in the fractions collected in the pH range 7.0–3.0. Results Receiver operating characteristics (ROC) analysis revealed that 36% of complete hydatidiform mole patients with post-molar persistent trophoblastic disease development had different hCG glycoform profiles at 97% specificity (pH interval 6.3–5.1, hCG cutoff 9.9%). There was a significant difference between complete hydatidiform mole with and without persistent trophoblastic disease for the cumulative percent amounts of hCG in the pH interval 6.3–5.1 ( p < 0.0003). Conclusion In 36% of the patients with complete hydatidiform mole with subsequent development of persistent trophoblastic disease, typical glycoform profiles for hCG are observed in pre-evacuation serum samples. This result suggests that hCG glycoform profiles are of potential use in the prediction of persistent trophoblastic disease.

Clinical utility of hyperglycosylated hCG in serum taken before hydatidiform mole evacuation to predict persistent trophoblastic disease

Human chorionic gonadotropin (hCG) is widely used in the management of hydatidiform mole and persistent trophoblastic disease (PTD). Studies on hyperglycosylated human chorionic gonadotropin (invasive trophoblast antigen, ITA) in PTD are limited. In serum samples taken before evacuation of molar pregnancies we measured the concentrations of free hCG beta-subunit (free hCGbeta), "total" hCG (hCG+hCGbeta) and ITA, and determined whether ITA, the two other hCG analytes, or the calculated ratios of hCGbeta/hCG+hCGbeta, hCGbeta/ITA and hCG+hCGbeta/ITA could predict the later development of PTD.A retrospective study based on blood specimens collected in the Dutch Central Registry for Hydatidiform Moles. The study group comprised 97 patients with hydatidiform moles who did not develop PTD after mole evacuation and 33 patients who did develop PTD.Serum samples from 130 patients with hydatidiform mole with or without PTD were assayed using specific (radio)immunoassays for free hCGbeta, total hCG, and ITA. From these analytes we also calculated the ratios hCGbeta/hCG+hCGbeta, hCGbeta/ITA, and hCG+hCGbeta/ITA. To predict the development of PTD from these analytes and parameters we performed receiver-operating characteristic (ROC) curve analysis, resulting in areas under the curve (AUCs) that represented the diagnostic accuracy which was rated in a range from excellent (AUC >0.9 or <0.1) to poor (AUC 0.4-0.6).The diagnostic accuracy of ITA was moderate (0.618) and not different from that of free hCGbeta (0.610) and hCG+hCGbeta (0.622).ITA as well as the other analytes and parameters in serum taken prior to evacuation from patients with molar pregnancies cannot be used to predict the subsequent development of persistent trophoblastic disease.

Clinical Utility of Hyperglycosylated hCG in Serum Taken before Hydatidiform Mole Evacuation to Predict Persistent Trophoblastic Disease

Human chorionic gonadotropin (hCG) is widely used in the management of hydatidiform mole and persistent trophoblastic disease (PTD). Studies on hyperglycosylated human chorionic gonadotropin (invasive trophoblast antigen, ITA) in PTD are limited. In serum samples taken before evacuation of molar pregnancies we measured the concentrations of free hCG beta-subunit (free hCGbeta), "total" hCG (hCG+hCGbeta) and ITA, and determined whether ITA, the two other hCG analytes, or the calculated ratios of hCGbeta/hCG+hCGbeta, hCGbeta/ITA and hCG+hCGbeta/ITA could predict the later development of PTD. A retrospective study based on blood specimens collected in the Dutch Central Registry for Hydatidiform Moles. The study group comprised 97 patients with hydatidiform moles who did not develop PTD after mole evacuation and 33 patients who did develop PTD. Serum samples from 130 patients with hydatidiform mole with or without PTD were assayed using specific (radio)immunoassays for free hCGbeta, total hCG, and ITA. From these analytes we also calculated the ratios hCGbeta/hCG+hCGbeta, hCGbeta/ITA, and hCG+hCGbeta/ITA. To predict the development of PTD from these analytes and parameters we performed receiver-operating characteristic (ROC) curve analysis, resulting in areas under the curve (AUCs) that represented the diagnostic accuracy which was rated in a range from excellent (AUC >0.9 or <0.1) to poor (AUC 0.4-0.6). The diagnostic accuracy of ITA was moderate (0.618) and not different from that of free hCGbeta (0.610) and hCG+hCGbeta (0.622). ITA as well as the other analytes and parameters in serum taken prior to evacuation from patients with molar pregnancies cannot be used to predict the subsequent development of persistent trophoblastic disease.

Methylation status and expression of E-cadherin and cadherin-11 in gestational trophoblastic diseases

The clinical significance of cadherins in gestational trophoblastic diseases (GTD) is not fully understood. In this study, the expression of E-cadherin and cadherin-11 in 12 normal placentas, 32 cases of hydatidiform mole (HM) including 15 complete HMs and 17 partial HMs, and five choriocarcinomas was investigated by immunohistochemistry and correlated with follow-up of HMs. Cases with available frozen blocks were further analyzed by western blot and semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Methylation of E-cadherin was investigated by methylation-specific PCR in six normal first trimester placentas, 19 HMs and their associated deciduas. E-cadherin expression was localized to cytotrophoblast and intermediate trophoblast whereas cadherin-11 was expressed in syncytiotrophoblast, intermediate trophoblast, and decidua. Immunoreactivity of E-cadherin was reduced in choriocarcinoma and complete HM when compared with that in normal first trimester placenta (P&lt; 0.01,P= 0.04). Hypermethylation of E-cadherin was demonstrated in three complete HMs with the lowest level of E-cadherin. Compared with normal first trimester placenta, immunoreactivity of cadherin-11 was higher in complete HM (P= 0.02), but lower in choriocarcinoma (P= 0.02). Such differential expression was confirmed by western blot and semiquantitative RT-PCR. No obvious association was observed between the development of persistent trophoblastic disease with the expression of E-cadherin and cadherin-11.

Expression of human telomerase reverse transcriptase, the catalytic subunit of telomerase, is associated with the development of persistent disease in complete hydatidiform moles

Objective: This study was undertaken to determine the putative role of telomerase activity and human telomerase reverse transcriptase (hTERT) expression in the development of persistent disease in patients with a diagnosis of complete hydatidiform mole. The ribonucleoprotein telomerase has been shown to have a major role in the process of cellular immortality and carcinogenesis. The reactivation of this enzyme that occurs in the development of malignancies appears to be limited by the regulation of its catalytic subunit hTERT. Compared with their somatic counterparts, most human malignancies demonstrate telomerase activity, and this activity is dependent on the cellular presence of hTERT. The role of telomerase in the pathogenesis of complete hydatidiform moles is not clearly understood. Moreover, the role of hTERT in trophoblastic disease, as well as in the development of persistent trophoblastic disease, has yet to be elucidated. Study Design: Telomerase activity and hTERT expression were analyzed in the initial uterine evacuation specimen of 54 complete hydatidiform moles by use of the telomeric repeat amplification protocol assay and reverse transcription–polymerase chain reaction methods. The results were compared and then correlated with the development of persistent trophoblastic disease. Results: Among the 54 patients who were examined with a diagnosis of complete hydatidiform mole, persistent trophoblastic disease requiring postevacuation chemotherapy developed in 6. In the remaining 48 patients, spontaneous remission of the disease occurred after uterine evacuation. Both telomerase activity and hTERT expression were detected in all 6 cases of persistent disease on the initial molar tissue sampled. Among the 48 nonpersistent moles, telomerase activity was detected in 29 (60%) and hTERT expression was demonstrated in 26 (54%). The detection of hTERT expression was significantly associated with the presence of persistent disease ( P = .035). Moreover, the absence of hTERT expression in molar tissue obtained from uterine evacuation demonstrated a 100% negative predictability in determining cases of complete mole that were nonpersistent. Conclusions: Compared with telomerase activity, the expression of hTERT is significantly associated with the development of persistent disease in complete hydatidiform moles. The absence of hTERT expression in the initial tissue sample from complete moles may have potential clinical value in determining patients who will eventually undergo spontaneous remission after uterine evacuation. (Am J Obstet Gynecol 2001;184:1441-6.)

Expression of nm23-H1 in Hydatidiform Mole and Its Relationship with the Development of Postmolar Disease

The aim of the present study was to investigate the expression of nm23-H1 in human placenta, hydatidiform mole and choriocarcinoma cells. Nm23-H1 protein was localized in the cytotrophoblast, but not in the syncytiotrophoblast. In the hydatidiform mole cases with subsequent spontaneous remission, nm23-H1 mRNA levels were significantly lower than those in first-trimester placentas. However, its levels were elevated in the hydatidiform mole cases that progressed to persistent gestational trophoblastic disease and were comparable to those of first-trimester placentas, and they were further elevated in choriocarcinoma cells. The present data suggest an association of nm23-H1 for the proliferation activity of trophoblast, and its increased expression may influence the development of persistent trophoblastic disease.

Telomerase activity in gestational trophoblastic disease.

AIMS: To investigate the pattern of telomerase activity in hydatidiform mole as compared with normal placenta and choriocarcinoma, and to determine the prognostic significance of telomerase activity in hydatidiform mole....

Serum and tissue vascular endothelial growth factor levels in hydatidiform mole

Using a specific and sensitive enzyme immunoassay for vascular endothelial growth factor (VEGF), we measured the circulating levels of VEGF in patients with hydatidiform mole as well as in maternal serum during normal pregnancy. VEGF levels in maternal serum were elevated at 7 weeks and then fell to a plateau. Serum VEGF levels were increased in patients with hydatidiform mole above the normal pregnant levels, while no differences were seen related to the development of persistent trophoblastic disease. By semi-quantitative RT-PCR in molar tissue for VEGF and placenta growth factor, a member of VEGF family, neither of the mRNA levels have no relation to the development of persistent trophoblastic disease. These observations suggest serum VEGF levels will be of value as a new circulating marker of hydatidiform mole.

Preevacuation Serum CA 125 in Complete Hydatidiform Mole

Studies on CA 125 in hydatidiform mole are limited. The objective of this study was to measure the preevacuation serum CA 125 level in patients with complete hydatidiform mole and to determine whether it could predict the later development of persistent trophoblastic disease. Preevacuation serum CA 125 levels were immunoradiometrically measured in 69 patients with histologically confirmed complete hydatidiform mole. The mean (range) serum CA 125 level was 63.7 (10.5–404.7) U/ml. Using 35 U/ml as the cutoff point, the elevated CA 125 levels were observed in 53.6% (37/69) of the patients. The mean serum CA 125 level of patients who later developed persistent trophoblastic disease was not significantly higher than that of those who had benign course (78.9 vs 52.6 U/ml,P> 0.05). In conclusion, the preevacuation serum CA 125 level was elevated in about half of patients with complete hydatidiform mole and it could not be used to predict the subsequent development of persistent trophoblastic disease.

Acute pulmonary edema associated with molar pregnancies: A high-risk factor for development of persistent trophoblastic disease

Acute pulmonary edema associated with molar pregnancies: A high-risk factor for development of persistent trophoblastic disease