Beta Subunit Of Chorionic Gonadotropin Research Articles

Gonadal germ cell tumors in children and adolescents.

Pediatric germ cell tumors (GCT) are rare tumors: 80% are benign, 20% malignant (2-3% of all malignant pediatric tumors). The gonadal sites (ovary and testis) account for 40% of cases.Ovarian GCTs:Represent 30% of GCTs and 70% of neoplastic ovarian masses, being the most common ovarian neoplasms in children and teenagers. Benign and immature forms (teratomas) constitute about 80% of all ovarian GCTs, malignant forms represent 20% increasing during adolescence. The most common malignant entity in children is the yolk sac tumors (YST); dysgerminoma is frequent during adolescence and being bilateral in 10% of cases. Presentation is similar in malignant and benign lesions; abdominal pain (70-80%) and lower abdominal mass are common symptoms. Evaluation of alpha-fetoprotein (αFP) or beta subunit of human chorionic gonadotropin (βHCG) is essential to address the nature of the tumors: Their elevation means presence of malignancy. Surgery includes intraoperative staging procedures and requires ovariectomy or ovarosalpingectomy for malignant lesions, but may be conservative in selected benign tumors. Since malignant GCTs are very chemosensitive, primary chemotherapy is recommended in metastatic or locally advanced tumors.Testicular GCT:Represent 10% of pediatric GCT, and about 30% of malignant GCT with two age peaks: Children <3 years may experience mature teratoma and malignant GCTs, represented almost exclusively by YST, while adolescents may also show seminomas or other mixed tumors. The main clinical feature is a painless scrotal mass. Surgery represents the cornerstone of the management of testicular GCTs, with an inguinal approach and a primary high orchidectomy for malignant tumors, while a testis-sparing surgery can be considered for benign lesions. A retroperitoneal lymph node (LN) biopsy may be necessary to define the staging when the involvement of retroperitoneal LN is uncertain at imaging investigations.Conclusion:Patients with gonadal malignant GCTs fare better than those with extragonadal mediastinal germ cell tumors (MGCTs) and survival rate exceeds 90% in localized forms. Chemotherapy has significantly improved the outcome of malignant forms since the introduction of platinum based regimens. The surgical procedure has to be performed in agreement with the ongoing protocols.

First trimester aneuploidy screening program for preeclampsia prediction in a portuguese obstetric population.

Objective. To evaluate the performance of a first trimester aneuploidy screening program for preeclampsia (PE) prediction in a Portuguese obstetric population, when performed under routine clinical conditions. Materials and Methods. Retrospective cohort study of 5672 pregnant women who underwent routine first trimester aneuploidy screening in a Portuguese university hospital from January 2009 to June 2013. Logistic regression-based predictive models were developed for prediction of PE based on maternal characteristics, crown-rump length (CRL), nuchal translucency thickness (NT), and maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-subunit of human chorionic gonadotropin (free β-hCG). Results. At a false-positive rate of 5/10%, the detection rate for early-onset (EO-PE) and late-onset (LO-PE) PE was 31.4/45.7% and 29.5/35.2%, respectively. Although both forms of PE were associated with decreased PAPP-A, logistic regression analysis revealed significant contributions from maternal factors, free β-hCG, CRL, and NT, but not PAPP-A, for prediction of PE. Conclusion. Our findings support that both clinical forms of EO-PE and LO-PE can be predicted using a combination of maternal history and biomarkers assessed at first trimester aneuploidy screening. However, detection rates were modest, suggesting that models need to be improved with additional markers not included in the current aneuploidy screening programs.

Human Chorionic Gonadotropin Beta Subunit Genes CGB1 and CGB2 are Transcriptionally Active in Ovarian Cancer

Human chorionic gonadotropin beta subunit (CGB) is a marker of pregnancy as well as trophoblastic and nontrophoblastic tumors. CGB is encoded by a cluster of six genes, of which type II genes (CGB3/9, 5 and 8) have been shown to be upregulated in relation to type I genes (CGB6/7) in both placentas and tumors. Recent studies revealed that CGB1 and CGB2, originally considered as pseudogenes, might also be active, however, the protein products of these genes have not yet been identified. Our study demonstrates the presence of CGB1 and CGB2 transcripts in ovarian carcinomas. While CGB1 and CGB2 gene activation was not detected in normal ovaries lacking cancerous development, our study demonstrates the presence of CGB1 and CGB2 transcripts in 41% of analyzed ovarian cancer cases.

Evaluación del índice de riesgo del primer trimestre en casos de embarazo múltiple con presencia de un feto perdido

Background and purposeTo justify an accurate assessment of the first-trimester combined screening test, in special cases of twin pregnancies with a vanishing twin; because the increase in such cases specially is being seen in pregnant women undergoing in vitro fertilization techniques. Patients and methodsWe report a case of biamniotic bichorionic twin pregnancy with loss of the first fetus at week 12. Prenatal screening was asked in wich it couldn’t been estimated the risk index for the first trimester screening test. Discussion and conclusionsThe risk index is not calculable due to the loss of one fetus. The levels of the free fraction of the beta subunit of human chorionic gonadotropin (β-hCG) in serum are not affected but there is a significant increase in the levels of pregnancy associated plasma protein-A (PAPP-A), which depends on the time since fetal loss; so the serum levels cannot be regarded neither as an isolated fetus or as 2. Therefore to assess the risk of the first-trimester combined screening test, it is recommended to estimate the fetal nuchal translucency thickness (NT) and β-hCG, or just only NT, also considering the median multiples (MoM) within the normal limits.

Frequency of Live Deliveries Despite at Least One Human Chorionic Gonadotropin Beta Subunit Failing to Double in Two Days

A previous study at our infertility center evaluated 158 consecutive pregnancies. There were 22 slow rising beta-hCG levels with at least one serum level which did not double in 2 days up to a 10,000 mIU/mL. There were 16 of the 22 pregnancies that showed fetal viability at 8 weeks but not at 12. The other 6 failed to show fetal viability at 8 weeks.

L’élévation du taux de bêta-HCG doit-elle être un critère d’exclusion des essais thérapeutiques ? À propos d’un cas de sécrétion paranéoplasique associée à un adénocarcinome bronchique

We report the case of a 55-year-old woman with pulmonary adenocarcinoma and bone metastases who was diagnosed with paraneoplastic secretion of the beta subunit of human chorionic gonadotropin (beta-HCG) while being screened for inclusion in a clinical trial. Immunohistochemistry analysis of a bone biopsy revealed strong staining of cancer cells with anti-beta HCG antibodies. Serial measurements of circulating Beta HCG seemed to be influenced by antineoplastic treatments, although they were not strictly associated with tumour evolution assessed by CT scans. Little is known about paraneoplastic secretion of beta HCG, although it has been found in 12% to 24% of non-small cell lung cancers. Usefulness of serial measurements of beta HCG for monitoring NSCLC has yet to be demonstrated, but its use as a criterion for inclusion in clinical trials needs to be questioned.

Ectopic pregnancy after right annessiectomy and left tubal ligation: case report

Objective. We report an unusual case of ectopic pregnancy in a woman with right annessiectomy and left tubal ligation. Case report. A 35-year old woman underwent laparotomy right annessiectomy and left tubal ligations, because of a mature cystic teratoma attached to the right annex. She arrived in emergency three years later with lower abdominal pain, amenorrhea and a positive level of beta hCG (Beta subunit of human chorionic gonadotropin). An urgent videolaparoscopy was performed, with a left salpingectomy with the removal of the ectopic pregnancy in the distal remain tube. The pathologic report confirmed the diagnosis of ectopic pregnancy. The patient’s postoperative recovery was normal. Conclusion. The analysis of the literature/published data shows that the partial salpingectomy increases the risk of ectopic pregnancy, so total salpingectomy is the preferred option over partial salpingectomy, in order to reduce the risk of recurrent ectopic pregnancy.

Second trimester screening for trisomy 21 using ADAM12-S as a maternal serum marker

To investigate the value of a disintegrin and metalloproteinase 12 secreting form (ADAM12-S) as a maternal serum marker in second trimester screening for trisomy 21 (Down syndrome, DS), and to develop an appropriate prenatal DS screening protocol. Serum samples were collected from 53 pregnant women carrying a trisomy 21 fetus and 621 pregnant women with matched gestational age and weight carrying a healthy fetus. ADAM12-S concentrations were determined with a time-resolved fluorescence immunoassay (TRFIA). Curve fitting by weighted regression and other statistical methods were conducted, and the model was optimized for prenatal trisomy 21 screening program in second trimester. ADAM12-S alone or in combination with other two- or three-combination test was selected as a serum marker for prenatal second-trimester screening of trisomy 21 by calculation of detection rate (DR) and false positive rate (FPR). By comparison, the median multiple of the median (MoM) value of ADAM12-S in DS pregnancy group was higher than that of the control group (P< 0.01). When FPR = 5%, the DR of ADAM12-S was 28.3%, and the positive and negative likelihood ratios were 5.66 and 0.75, respectively. The DR of three-combination test of ADAM12-S, alpha-fetoprotein (AFP) and free beta subunit of human chorionic gonadotropin (β-HCG) has increased to 52.80% from 39.62% of the conventional two-combination test (AFP and free β-HCG). For women with a risk between 1/300 and 1/1000 by two-combination test for DS, the DR has increased from 39.62% to 47.12%, but FPR only increased by 0.8% after adding ADAM12-S as a maternal serum marker. Considering the increased DR of pregnancies with a risk between 1/300 and 1/1000 in second trimester, ADAM12-S may provide a feasible maternal serum maker when combined with AFP and free β-HCG. The cost-effectiveness ratio is reasonable.

Role of first-trimester free beta subunit of human chorionic gonadotropin (β-HCG) and pregnancy-associated plasma protein-A (PAPP-A) as markers for intrauterine fetal growth restriction

Intrauterine growth restriction (IUGR) is a major determinant of perinatal morbidity and mortality. Standard diagnostic methods like sonography are accurate, but they can not be employed as the screening tools. Lately, it has been proposed that there might be an association between IUGR and placental dysfunction; hormones such as human chorionic gonadotropin-beta subunit (β-HCG) and pregnancy-associated plasma protein-A (PAPP-A) may be good early indicators of unwanted outcomes. This study is aimed at evaluating the possible association of serum free β-HCG and PAPP-A levels in the first trimester with IUGR in chromosomaly normal pregnancies. In this cohort study, 1440 normal singleton pregnancies were evaluated in Tabriz Alzahra Teaching Hospital during a 17-month period. Serum free β-HCG and PAPP-A levels were measured in women at 10 to 14 weeks of pregnancy by enzyme linked immunosorbent assay (ELISA). All the women were followed up to determine the time of delivery and to be categorized as with or without IUGR. Serum free β-HCG and PAPP-A levels were compared between the groups. The rate of IUGR was 4.4%. The mean serum levels of free β-HCG and PAPP-A were 2.6±2.7 (range: 0.1 to 10.8, median: 0.9) M.O.M (multiples of the median) 2.4±2.6 (range: 0.1 to 8.9, median: 0.9) MoM, respectively. The median serum β-HCG was 1 and 0.9 MoM in cases with normal and IUGR pregnancies, respectively (p=0.587). The median serum PAPP-A was significantly lower in patients with IUGR (0.7 vs. 0.9 MoM; p=0.044). The optimal cut-off point for PAPPA was 0.79 MoM with sensitivity and specificity of 51 and 54%, respectively. This study showed that low level of serum PAPP-A but not β-HCG during the first trimester is associated with IUGR. Key words: Fetal growth restriction, human chorionic gonadotropin-beta subunit, pregnancy-associated plasma, protein-A.

Recent advances in diagnostics of trophoblastic disease

Gestational trophoblastic disease (GTD) is a term used for a group of pregnancy-related tumours, overwhelmingly affecting women of childbearing age. These tumours are rare, and they appear when trophoblastic cells start to grow out of control. In these conditions production of beta subunit of human chorionic gonadotropin (hCG) is evident. Hydatidiform moles, partial or complete, are in most cases benign featured by villous hydrps, scalloping effect, hyperplastic trophoblastic pseudoinclusions and syncytiotrophoblastic sprouts. Invasive mole is an aggressive trophoblastic lesion with myometrial and/or vascular invasion. Choriocarcinoma, placental site trophoblastic tumor and epitheloid trophoblastic tumor are clearly malignant tumors with proliferation of intermediate trophoblast, with metastatic potential. Tumor-like trophoblastic conditions are placental site nodul and exaggerated placental site which are proliferative lesions and reactive processes and are not considered as true tumor lesions. In all of these conditions vaginal bleeding is the most common symptom followed by elevation of serum beta hCG. GTD has to be confirmed histologically with extensive sampling of the material. Follow up is necessary in all women with GTD and it is rutinley done by measurement of serum levels of hCG. Since GTDs are proliferative conditions of different trophoblastic tissues, pathologists should be well histologicly educated about normal pregnancy stages and its abnormalities in order of adequate diagnosing these rare conditions.

Validation of a new multiplex assay against individual immunoassays for the quantification of reproductive, stress, and energetic metabolism biomarkers in urine specimens

Measuring multiple hormones simultaneously in a single assay saves sample volume, labor, time, reagents, money, and consumables. Thus, multiplex arrays represent a faster, more economically and ecologically sound alternative to singleton assays. To validate a new, commercially available multiplex female array produced by Quansys Biosciences against individual immunoassays for the quantification of six hormones in urine samples from women in different reproductive stages. Urine samples were analyzed using the new Quansys multiplex female hormone array and compared with well-established individual immunoassays for adiponectin, free cortisol, c-peptide, estrone-3-glucuronide (E₁G), follicle stimulating hormone beta-subunit (FSH-beta), and human chorionic gonadotropin beta-subunit (hCG-beta). Correlations between assays were assessed using Pearson correlation, linear regression and Bland-Altman analysis. The temporal profiles of free cortisol, E1G, FSH-beta, and hCG-beta were also compared. The multiplex array was highly correlated with the individual immunoassays for five of the tested hormones (Pearson's correlation coefficient ≥ 0.75), and yielded temporal patterns of hormone profiles consistent with the individual immunoassays for free cortisol, E₁G, FSH-beta, and hCG-beta. The Quansys multiplex female hormone array is a valid alternative method to individual immunoassays for the quantification of stress, reproductive and energetic hormones and metabolites in human urine samples and can be used to examine the dynamic interactions between these hormones.

CGB and GNRH1 expression analysis as a method of tumor cells metastatic spread detection in patients with gynecological malignances

BackgroundMetastasis is a common feature of many advanced stage cancers and metastatic spread is thought to be responsible for cancer progression. Most cancer cells are localized in the primary tumor and only a small population of circulating tumor cells (CTC) has metastatic potential. CTC amount reflects the aggressiveness of tumors, therefore their detection can be used to determine the prognosis and treatment of cancer patients.The aim of this study was to evaluate human chorionic gonadotropin beta subunit (CGB) and gonadoliberin type 1 (GNRH1) expression as markers of tumor cells circulating in peripheral blood of gynecological cancer patients, indicating the metastatic spread of tumor.MethodsCGB and GNRH1 expression level in tumor tissue and blood of cancer patients was assessed by real-time RT-PCR. The data was analyzed using the Mann-Whitney U and Spearman tests. In order to distinguish populations with homogeneous genes' expression the maximal likelihood method for one- and multiplied normal distribution was used.ResultReal time RT-PCR results revealed CGB and GNRH1 genes activity in both tumor tissue and blood of gynecological cancers patients. While the expression of both genes characterized all examined tumor tissues, in case of blood analysis, the transcripts of GNRH1 were found in all cancer patients while CGB were present in 93% of patients. CGB and GNRH1 activity was detected also in control group, which consisted of tissue lacking cancerous changes and blood of healthy volunteers. The log-transformation of raw data fitted to multiplied normal distribution model showed that CGB and GNRH1 expression is heterogeneous and more than one population can be distinguished within defined groups.Based on CGB gene activity a critical value indicating the presence of cancer cells in studied blood was distinguished. In case of GNRH1 this value was not established since the results of the gene expression in blood of cancer patients and healthy volunteers were overlapping. However one subpopulation consists of cancer patient with much higher GNRH1 expression than in control group was found.ConclusionsAssessment of CGB and GNRH1 expression level in cancer patients' blood may be useful for indicating metastatic spread of tumor cells.

Impact of type 1 diabetes and glycemic control on fetal aneuploidy biochemical markers

To determine the influence of type 1 diabetes mellitus (T1DM) on the first trimester serum markers of fetal aneuploidy; pregnancy-associated plasma protein-A (PAPP-A) and free beta subunit of human chorionic gonadotropin (free β-hCG) and to evaluate the influence of glycemic control on these parameters in the pregnant diabetic women. Retrospective study. Data were extracted from electronic obstetric and laboratory databases at two Danish University Hospitals. Based on 36 415 pregnancies without T1DM (non-T1DM) and 331 pregnancies with T1DM; β-hCG and PAPP-A were obtained at 8+0 to 14+2 gestational weeks. Medians for PAPP-A and free β-hCG were generated and multiple of the normal gestation-specific median (MoM) values were calculated for each separate pregnancy. After adjustment for maternal weight, ethnicity and smoking status, MoM values were compared across the T1DM and non-T1DM groups, respectively. Additionally, the relationship between PAPP-A MoM and HgbA1C was examined in 348 T1DM pregnancies by Spearman's rank correlation. MAIN OUTCOME MEASURES. Difference in biochemical marker levels between T1DM and non-T1DM. PAPP-A was 0.86 MoM in T1DM pregnancies and 1.01 MoM in non-T1DM pregnancies, p < 0.0001. Conversely, free β-hCG was not altered in T1DM pregnancies (T1DM 0.99 MoM, non-T1DM 0.98 MoM; p=0.14). There was a significant inverse correlation between HgbA1C and PAPP-A (rho=-0.12, p=0.02). In T1DM pregnancies, PAPP-A MoM values were lower than in non-T1DM pregnancies. This suggests that correction should be considered in first trimester biochemical screening for fetal aneuploidy in T1DM women.

Cell specific patterns of methylation in the human placenta

Epigenetic processes, such as DNA methylation, are known to regulate tissue specific gene expression. We explored this concept in the placenta to define whether DNA methylation is cell-type specific. Cytotrophoblasts and fibroblasts were isolated from normal midtrimester placentas. Using immunocytochemistry, we demonstrated 95% purity for cytotrophoblasts and 60-70% for fibroblasts. We compared DNA methylation profiles from cytotrophoblasts, fibroblasts and whole placental villi using bisulfite modified genomic DNA hybridized to the Illumina Methylation27 array. Euclidean cluster analysis of the DNA methylation profiles showed 2 main clusters, one containing cytotrophoblasts and placenta, the other fibroblasts. Differential methylation analysis identified 442 autosomal CpG sites that differed between cytotrophoblasts and fibroblasts, 315 between placenta and fibroblasts and 61 between placenta and cytotrophoblasts. Three candidate methylation differences were validated by targeted pyrosequencing assays. Pyrosequencing assays were developed for CpG sites less methylated in cytotrophoblasts than fibroblasts mapping to the promoter region of the beta subunit of human chorionic gonadotropin 5 (CGB5), as well as 2 CpG sites mapping to each of 2 tumor suppressor genes. Our data suggest that epigenetic regulation of gene expression is likely to be a key factor in the functional specificity of cytotrophoblasts. These data are proof of principle for cell-type specific epigenetic regulation in placenta and demonstrate that the methylation profile of placenta is mainly driven by cytotrophoblasts.

Gastric cancer with choriocarcinoma and yolk sac tumor components: Case report

Choriocarcinoma- and yolk sac tumor-like differentiation have rarely been reported in gastric cancers. We report a case of gastric adenocarcinoma, concurrently possessing choriocarcinoma and yolk sac tumor components, of a 74-year-old man. A hemorrhagic, 11 × 8 × 3 cm, tumor with ulceration was located in the body and pre-pylorus of the stomach. Histological examination of the resected specimens demonstrated intermingled proliferation of three different components, namely, adenocarcinoma, choriocarcinoma and yolk sac tumor, which were immunoreactive for carcinoembryonic antigen (CEA), beta-subunit of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP), respectively. Gastric cancers with germ cell tumor components are uncommon and this is the second reported case of gastric cancer with choriocarcinoma and yolk sac tumor components.

Prospective experience with contingent screening strategy for Down syndrome in Estonia

The purpose of this study was to establish the first-trimester screening for Down syndrome (DS) in Estonia and to evaluate the potential of a contingent screening in the population of pregnant women. A prospective cohort study included non-selected pregnancies during the programme of first-trimester screening for DS in a 4-year period at a single centre. The following screening tests were evaluated: measurement of nuchal translucency (NT) and serum screening [pregnancy-associated plasma protein A and free beta subunit of human chorionic gonadotropin (fβ-HCG)]; results were given as combined screening. After first-trimester screening, contingent screening protocol was used, and women were divided into three groups: high risk, low risk and an intermediate risk group. In the last group, a second-trimester triple test (AFP; total HCG and uE3) was also performed. The study group consisted of 3,194 non-selected pregnancies. In 1,387 (43.4%) women, first-trimester serum screening showed low risk (risk ≤ 1:5,000), and no future testing was performed, in 30 (0.9%) women screening test showed high risk (risk ≥ 1:50) and a diagnostic test was offered, and in 1,777 (55.7%) women repeated risk calculation in the second trimester was done. During the study period, there were 17 cases of trisomy 21, of which 15 (88.3%) were detected with the described screening programme. In conclusion, two-step contingent sequential screening is a better choice for Down syndrome screening in Estonia instead of previously used second-trimester screening, and it offers the advantage of earlier diagnosis.

Identification of universal mRNA markers for noninvasive prenatal screening of trisomies

The discovery of placental transcripts in peripheral blood of pregnant women prompted us to investigate which was the most appropriate biological specimen, between plasma and serum, to easily detect them and to exploit hPL (human placental lactogen), betahCG (human chorionic gonadotrophin beta-subunit), LOC90625, and TFPI2 (tissue factor pathway inhibitor 2) levels in order to establish whether an abnormal variation degree of presence of these placental transcripts are likely to be associated to specific fetal trisomies. RNA was extracted from plasma and serum samples of 255 pregnant women bearing euploid fetuses, 17 bearing fetuses affected by trisomy 21 and 10 with fetuses affected by trisomy 18. Placental transcript analysis was performed by real time RT-PCR using relative quantification. Results obtained from euploid samples showed that fetal transcripts were more abundant in plasma than in serum samples. Euploid samples had a placental transcript abundance distinguishable from those with trisomy 21 but not from those with trisomy 18. In particular, high betahCG abundance and advanced maternal age were significantly associated with trisomy 21 pregnancy. Plasma was the most suitable tool to be employed in the detection and dosage of placental transcripts. betahCG transcript together with maternal age could be a potential marker for noninvasive prenatal screening of fetal trisomy 21.

Chorangiocarcinoma: A Case Report and Review of the Literature

Chorangiocarcinoma is the name designated to a chorangioma with trophoblastic proliferation manifesting increased proliferative activity. Only 3 such cases have been published so far. Other studies challenged this entity by demonstrating that proliferation of the trophoblast around chorangioma is a common phenomenon. We present a case of a unique vascular lesion in a term placenta with a malignant trophoblastic component. Microscopic examination of a well-demarcated placental mass revealed a chorangioma with multiple nodules composed of pleomorphic cells displaying focal multinucleation, large areas of necrosis, and high mitotic activity. Immunohistochemical stains of these cells were strongly positive for pancytokeratin and the beta subunit of human chorionic gonadotropin and focally positive for HSD3B1. There was no invasion of the basement membrane, and no free-floating tumor cells in the intervillous space. No evidence of metastasis was found on follow-up of the mother and newborn. It is concluded that the tumor presented herein, displaying a histologically unequivocal malignant trophoblastic component in a benign chorangioma, is a true chorangiocarcinoma, and should be included within the category of gestational neoplasia as a tumor closely related to choriocarcinoma.

Fusion of Villous Trophoblast can be Visualized by Localizing Active Caspase 8

Villous cytotrophoblast differentiation and subsequent fusion with the overlying syncytiotrophoblast depend on multiple factors such as growth factors, cytokines, hormones, protein kinases, transcription factors, structural membrane proteins and proteases. Caspase 8, an aspartate-specific cysteine protease, is mainly known for its role in programmed cell death, but was also demonstrated to be crucial for villous trophoblast differentiation. This study aimed to localize active caspase 8 in the villous trophoblast layer of human first trimester placenta. To this end, immunofluorescence double staining was performed, using a monoclonal rabbit antibody against cleaved caspase 8 in combination with antibodies against cytokeratin 7, chorionic gonadotropin beta subunit (βhCG), β-actin, placental protein 13 (PP13), α-fodrin and Ki-67. Immunofluorescence revealed cleaved caspase 8 in one out of 422 villous cytotrophoblasts resting on the basement membrane, in one out of 759 perinuclear regions within the syncytiotrophoblast and in few trophoblasts located between these two layers. Double staining of cleaved caspase 8 and Ki-67 antigen revealed that caspase 8 is activated only in cytotrophoblasts which have left the cell cycle. The staining suggests that caspase 8 is activated in villous cytotrophoblasts just prior to fusion of these cells and escorts the nuclei from the mononucleated to the syncytial state.

Clinical parameters predicting therapeutic response to surgical management in patients with chemotherapy-resistant gestational trophoblastic neoplasia

Objective Several studies have reported that surgical management of chemotherapy-resistant gestational trophoblastic neoplasia (GTN) is a useful adjunct to chemotherapy. We investigated the pretreatment predictive factors of therapeutic response in response to surgical management combined with chemotherapy. Methods The study involved 61 patients with chemotherapy-resistant GTN who underwent surgery between January 1996 and January 2007. Responses to the combination therapy with surgery and chemotherapy were assessed after the end of treatment. Statistical analyses were performed to identify preoperative clinical factors associated with response of chemotherapy-resistant GTN. Results After the end of combination therapy, 47 (77.0%), 4 (6.6%), 1 (1.6%), and 9 (14.8%) of 61 patients showed complete response (CR), partial remission (PR), stable disease (SD), and progressive disease (PD), respectively. Univariate analysis found that predictors of response were age ( p = 0.022), antecedent pregnancy ( p = 0.022), site of metastasis ( p = 0.026), and preoperative serum human chorionic gonadotropin-beta subunit (β-hCG) level ( p = 0.027). All patients with treatment failure had 2 or more of unfavorable factors, including age older than 35 years, antecedent non-molar pregnancy, distant metastasis outside of lungs and uterus, and preoperative serum β-hCG level greater than 10 IU/L. Conclusions The data suggest that age older than 35 years, antecedent non-molar pregnancy, distant metastasis outside of lungs and uterus, and a preoperative serum β-hCG level greater than 10 IU/L are important clinical predictors of treatment failure to surgery. They may benefit in the selection of salvage surgery as well as the assessment of individual prognosis.