Intensified therapies improve survival and identification of novel prognostic factors for placental-site and epithelioid trophoblastic tumours.

BACKGROUND: Placental-site trophoblastic (PSTT) and epithelioid trophoblastic tumours (ETT) are the rarest malignant forms of gestational trophoblastic disease (GTD). Our prior work demonstrated that an interval of ≥48 months from the antecedent pregnancy was associated with 100% death rate, independent of the stage. Here, we assess whether modified treatments for these patients have increased survival and identify new prognostic factors. METHODS: The United Kingdom GTD database was screened to identify all PSTT/ETT cases diagnosed between 1973 and 2014. Data and survival outcomes from our prior patient cohort (1976-2006) were compared to our new modern cohort (2007-2014), when intensified treatments were introduced. RESULTS: Of 54,743 GTD patients, 125 (0.23%) were diagnosed with PSTT and/or ETT. Probability of survival at 5 and 10 years following treatment was 80% (95% CI 72.8-87.6%) and 75% (95% CI 66.3-84.3%), respectively. Univariate analysis identified five prognostic factors for reduced overall survival (age, FIGO stage, time since antecedent pregnancy, hCG level, mitotic index) of which stage IV disease (HR 6.18, 95% CI 1.61-23.81, p = 0.008) and interval ≥48 months since antecedent pregnancy (HR 14.57, 95% CI 4.17-50.96, p < 0.001) were most significant on multivariable analysis. No significant differences in prognostic factors were seen between the old and new patient cohort. However, the new cohort received significantly more cisplatin-based and high-dose chemotherapy, and patients with an interval ≥48 months demonstrated an improved median overall survival (8.3 years, 95% CI 1.53-15.1, versus 2.6 years, 95% CI 0.73-4.44, p = 0.·005). CONCLUSION: PSTT/ETT with advanced FIGO stage or an interval ≥48 months from their last known pregnancy have poorer outcomes. Platinum-based and high-dose chemotherapy may help to improve survival in poor-prognosis patients.

Comparison of two assays measuring human chorionic gonadotrophin serum concentrations in pregnancy termination and trophoblastic or non-trophoblastic tumours.

BACKGROUND: Differences in human chorionic gonadotrophin (hCG) results provided by the commercial immunoassays reflect the heterogeneity of antibodies and the use of suboptimal standards. As a consequence, the principal forms of hCG and metabolites are differentially detected and the hCG tests are not suited for the same clinical applications. Conflicting results are available in the literature regarding which hCG variants are recognized by the Roche Elecsys hCG + ß test. The aim of our study was to compare the hCG concentrations provided by the Siemens Immulite 2000 test and the Roche test as well as to assess the concordance between both assays. METHODS: In this purpose, 152 samples obtained from women and 44 samples from men were analysed by both tests during the follow-up of pregnancy termination, gestational trophoblastic disease and malignancies. The intermediate precision of the Roche test was also investigated on a pool with a low hCG concentration. RESULTS AND CONCLUSIONS: The hCG concentrations measured with the Roche test were slightly lower compared with the Siemens assay; mean biases of -34.2% and -8% were respectively obtained for hCG values ≤100 UI/L and higher than 100 UI/L. The overall agreement between both assays was 96.1% for women and 97.7% for men. By using an upper reference limit of 3.2 UI/L for women and 1.6 UI/L for men, the Roche test demonstrated a respective concordance of 98.7% and 100%. This test also yielded an excellent precision with a coefficient of variation of 2.8% at a mean hCG concentration of 7 UI/L.

Pulmonary mass diagnosed as extrauterine epithelioid trophoblastic tumor.

Pulmonary extrauterine epithelioid trophoblastic tumors (ETTs) are extremely rare. A 26-year-old nonsmoking woman with a history of a suspected subclinical miscarriage presented with a large mass in the right lower lobe that was confirmed to be a pulmonary extrauterine ETT using immunohistochemical stains. When a nonsmoking fertile woman presents with a pulmonary mass and an elevated serum ß-human chorionic gonadotrophin in the absence of gynecologic disease, pulmonary extrauterine ETT should be considered.

May platelet count be a predictor of low-risk persistent gestational trophoblastic disease?

PURPOSE: The aim of this paper was to determine whether platelet count could be used as an early marker to predict low-risk persistent trophoblastic disease (PTD) from complete hydatidiform mole (CHM). METHODS: This study included 27 PTD, 30 CHM, and 30 healthy pregnant women. All patients were evaluated with respect to age, gestational age, parity, BMI, and platelet count. All women had low-risk disease using FIGO and WHO scoring systems. RESULTS: There were no significant differences in terms of age, gestational age, parity, BMI between the groups (P > 0.05, for all). Platelet levels were lower in patients with low-risk PTD compared with CHM and healthy pregnant group (P = 0.001 and P < 0.0001, respectively). Platelet levels were also found to be lower in patients with CHM than in healthy pregnancies (P = 0.006). There was a negative relationship between platelet count and low-risk PTD (r = 0.47, P < 0.0001) in the study. The receiver operating characteristic curve analysis revealed a high diagnostic value for platelet count with respect to low-risk PTD with an area under curve of 0.80 (95% confidence interval = 0.89-0.90), sensitivity = 77% and specificity = 75%. CONCLUSION: Platelet count was significantly decreased in low-risk PTD compared with CHM and healthy pregnant controls. Platelet count can be used as a reliable marker for the early detection of low-risk PTD.

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.

External validation of serum hCG cutoff levels for prediction of resistance to single-agent chemotherapy in patients with persistent trophoblastic disease.

Van Trommel et al have previously shown that serum human chorionic gonadotropin (hCG) cutoff levels can provide early prediction of resistance to first-line methotrexate (MTX) in patients with persistent trophoblastic disease (PTD). In this study, we validate this approach of prediction of resistance to single-agent chemotherapy in an independent and larger cohort of PTD patients using a different hCG assay. Receiver operating characteristics (ROC) curves were constructed to determine hCG cutoff levels and sensitivity between patients cured on single-agent chemotherapy (control group) and patients requiring change to combination chemotherapy (study group). Receiver operating characteristics analysis identified an hCG cutoff value of 737 IU l(-1) that enabled us to predict the subsequent development of single-agent chemotherapy resistance in 52% of patients before their fourth MTX course at 97.5% specificity. This would have enabled an earlier switch to combination chemotherapy reducing the MTX exposure by an average of 2.5 courses. The present findings confirm that serum hCG cutoff levels predict resistance to single-agent therapy earlier than traditional methods. Change to combination chemotherapy should be considered for patients whose serum hCG levels exceed these hCG cutoff values. For patients not exceeding the hCG cutoff levels, static or rising hCG levels should still be included in the criteria for change of chemotherapy.

Dedifferentiated endometrioid adenocarcinoma with trophoblastic components and elevated serum alfa-fetoprotein: A case report and literature review.

RATIONALE: Dedifferentiated endometrioid adenocarcinoma (DEAC) consisted of a combination of undifferentiated and differentiated carcinoma is more aggressive than other conventional endometrioid adenocarcinomas. PATIENT CONCERNS: A 33-year-old woman with atypical vaginal bleeding was refereed to our hospital. She had an endometrial biopsy in a local clinic which showed differentiated endometrioid carcinoma with trophoblastic components. High levels of ß-Human chorionic gonadotropin (ß-hCG) and alfa-fetoprotein (AFP) were detected in the patient's serum. INTERVENTIONS: The patient underwent total hysterectomy with bilateral salpingo-oophorectomy, total omentectomy and systemic pelvic lymphadenectomy in our center. DIAGNOSIS: Pathological investigation indicated that the tumor had well differentiated and undifferentiated adenocarcinoma as well as trophoblastic components. OUTCOMES: Serum ß-hCG and AFP dropped significantly after operation. But three weeks later, the patient had developed pulmonary metastases and elevation of serum ß-hCG. She died of the disease five months after surgery. LESSONS: DEAC with trophoblastic differentiation seems to follow an aggressive course with early metastasis and poor clinical prognosis. However, due to small number of cases, further studies are necessary.

Lowered reference limits for hCG improve follow-up of patients with hCG-producing tumors.

BACKGROUND: Human Chorionic Gonadotropin (hCG) is produced by germ cell tumors, but can also be elevated in benign conditions such as primary hypogonadism, where hCG is produced by the pituitary gland. In our experience, the reference limits for hCG (Elecsys hCG+ß-assay, Roche Diagnostics), were unnecessarily high and did not reflect levels encountered in clinical practice. We wanted to establish new reference limits to increase the clinical utility of the hCG-assay. METHODS: We analysed hCG in serum samples from a healthy adult population and in a cohort of testicular cancer survivors. The gonadotropins LH and FSH were measured in the cohort and in a selection of the reference population to assess gonadal function. RESULTS: We found low hCG levels for all men and women <45years (97.5 percentiles 0.1 and 0.2IU/L, respectively) from the healthy population (n=795) having normal FSH and LH. Due to assay limitations, we suggest a common reference limit of <0.3IU/L. For the age group ≥45, the 97.5 percentiles in the healthy population were 0.5IU/L for men and 6.0IU/L for women. In all subjects from both the reference population and the cohort (n=732), hCG levels exceeding the reference limit could be fully explained by reduced gonadal function indicated by elevated LH and FSH levels. CONCLUSION: The Elecsys hCG+ß-assay should have lower reference limits than recommended by the manufacturer, with important implications for tumor follow-up. Elevated hCG is rare with intact gonadal function, both in a normal population and among survivors of testicular cancer, and should lead to further investigations when encountered in clinical practice.

[Syndrome of persistent low levels of human chorionic gonadotrophin (hCG)]. / Syndrom perzistujících nízkých hladin humánních choriových gonadotropinu (hCG) etiologie, klasifikace, diagnostika, postupy.

OBJECTIVE: To analyze the syndrome of persistent low levels of hCG in terms of its etiology, classification, diagnosis, and management. DESIGN: Retrospective analysis. SETTING: Center for Trophoblastic Disease in Czech Republic, Institute for Care of Mother and Child, Prague, Institute of Postgraduate medical education, IPVZ, Prague METHODS: An analysis of the syndrome of persistent low levels of hCG recorded in CTN in 29 women in the years 1979-2005 by the immunoluminesence method which can quantitatively assess variable levels of hCG in blood and urine. A comparison was made of our findings with results of a similar studies having been done in England and USA. RESULTS: Persistent low levels of hCG (PLL) can be differentiated according to cause. 1. PLL-F False positive, also known as Phantom hCG, often caused by heterogenous antibodies. 2. PLL-H Of hypophysial origin, mainly in perimenopause and menopause. 3. PLL-Q Quiescent with trophoblastic disease in history, of trophoblastic origin. 4. PLL-U Undetermined, in history without trophoblastic disease, but in the past with physiological or pathological pregnancy. Assuming also to be of trophoblastic origin. All types of PLL lead in practice to the wrong diagnosis of trophoblastic disease and to a high percentage (40-80%) of needless chemotherapy and operations. In no case of PLL did chemotherapy or operations have an effect on PLL and thus are contraindicated. PLL-Q and PLL-U require continuous clinical and laboratory monitoring and repeated examinations with sophisticated visualization methods. The percentage of developing malignant trophoblastic tumors after PLL-Q and PLL-U is unclear. Extreme incidence was established in 7-25%. PLL-Q and PLL-U are considered as a marker of persistent trophoblastic invasion. Its detection by visualization methods in any organ localization before it turns into a limited solid tumor is excluded by it microscopic dissociative structure. CONCLUSION: The syndrome of persistent low levels of hCG (PLL) lately affects all gynecological and obstetrical workplaces. According to cause it can be divided into: 1. PLL false positive, 2. PLL of hypophysial origin, 3.PLL quiescent with trophoblastic disease in the history, 4. PLL undetermined, in history without trophoblastic disease. In the last two items mentioned above we assume to be of trophoblastic origin. Their morphological base is persistent trophoblastic invasion. The syndrome of PLL often leads to the wrong diagnosis of trophoblastic disease and to needless chemotherapy and operations. In this work was described the diagnosis of PLL, its classification, cause, and management. The percentage of PLL turned into malignant trophoblastic disease is unknown and ranges from 7-25% and requires monitoring in an accredited, national center for trophoblastic disease.

Low-risk persistent gestational trophoblastic disease: outcome after initial treatment with low-dose methotrexate and folinic acid from 1992 to 2000.

PURPOSE: We have simplified the treatment of gestational trophoblastic disease (GTD) in order to reduce the number of patients exposed to potentially carcinogenic chemotherapy. Patients who score 0 to 8 on the Charing Cross scoring system are classified as low-risk and receive methotrexate (MTX) and folinic acid (FA), whereas those who score higher than 8 are classified as high-risk and receive the etoposide, methotrexate, and dactinomycin (EMA)/cyclophosphamide and vincristine (CO) regimen. PATIENTS AND METHODS: Between 1992 and 2000, 485 women with GTD were commenced on MTX/FA at Charing Cross Hospital, London, United Kingdom. If patients developed MTX resistance or toxicity, treatment was altered according to the level of beta human chorionic gonadotropin (hCG). If serum hCG was < or = 100 IU/L, patients received dactinomycin; if hCG was greater than 100 IU/L, patients received EMA/CO. RESULTS: The median duration of follow-up was 4.7 years. Overall survival was 100% and the relapse rate was 3.3% (16 of 485 patients). hCG values normalized in 324 (66.8%) of 485 patients with MTX alone, whereas 161 (33.2%) of 485 patients required a change in treatment, 11 because of MTX toxicity and 150 because of MTX resistance. Sixty-seven patients changed to dactinomycin, of whom 58 achieved normal hCG values, and nine required third-line chemotherapy with EMA/CO. hCG values normalized in 93 (98.9%) of 94 patients who changed directly to EMA/CO from MTX. CONCLUSION: Single-agent dactinomycin has activity in patients with low-risk GTD who develop MTX resistance and whose hCG is low. Simplifying the stratification of GTD into two classes (low- and high-risk) does not compromise overall outcome and may reduce the risk of second tumors.

Monoclonal antibodies to the free beta-subunit of human chorionic gonadotropin define three distinct antigenic domains and distinguish between intact and nicked molecules.

The present study was designed to characterize monoclonal antibodies (mAbs) specific for the free beta-subunit of hCG (free hCG beta), to develop two-site immunoradiometric assays (m-IRMAs) specific for free hCG beta, and to study the reactivities of various molecular forms of hCG beta in these assays. We attempted first to delineate the antigenic regions present specifically on the free hCG beta by studying the binding pattern of seven mAbs directed preferentially to hCG beta, designated FBT11, P8E, P10F, HB2, P5D, P5H, and INN-64. Competitive inhibition experiments performed by RIA demonstrated the specificity of these mAbs for the free hCG beta as noncross-reacting with the beta-subunit of human (h) LH beta. m-IRMAs were used to analyze the arrangement of epitopes on hCG beta. Experiments performed with the seven mAbs used either as capture antibodies or radiolabeled indicators confirmed the specificity of the seven mAbs for the free hCG beta, and that mAbs FBT11, P8E, and P10F bound to equine LH beta (eLH beta), but did not bind to a fragment of hCG beta called the beta-core fragment (beta CF). These antibodies defined an antigenic domain identified as A. In contrast, mAb HB2 bound neither to eLH beta (e beta) nor to beta CF and was directed to domain B (e beta negative, beta CF negative). Finally, mAbs P5D, P5H, and INN-64 bound to beta CF, but did not bind to eLH beta, and defined a third domain identified as C (e beta negative, beta CF positive). Collectively, these results demonstrate that at least six antigenic domains are present on the free hCG beta and that a limited set of amino acids was shared among these domains; domains A, B, and C are present only on the free beta-subunit, while three other domains recognized by mAbs FB19, FBT10, and 518B7 are present on both free hCG beta and hCG. Thus, most of the surface of the hCG beta appears to be antigenic and accessible to antibody binding. Three different m-IRMAs specific for free hCG beta were then constructed using either mAb FBT11 (domain A) or HB2 (domain B). The study of the reactivities of various molecular forms of hCG beta in these assays demonstrated that the recognition of hCG beta forms nicked at position 43 (beta 43), 44, and/or 51 (beta 44/51) varied between assays.(ABSTRACT TRUNCATED AT 400 WORDS)

Radioimmunoassay of the serum free beta-subunit of human chorionic gonadotropin in trophoblastic disease.

We developed a RIA specific for the free beta hCG employing anti-beta hCG monoclonal antibody 1D12. This RIA was highly sensitive to free beta hCG; the minimum detectable concentration was 0.4 ng/ml. alpha hCG, LH, beta LH, and FSH had little effect in the assay; the cross-reactivity of hCG was about 4%. Using this RIA, we measured serum free beta hCG concentrations in 38 normal pregnant women and 72 untreated patients with 3 types of trophoblastic disease: hydatidiform mole (n = 15), invasive mole (n = 29), and choriocarcinoma (n = 28). All of these samples were simultaneously assayed for hCG by RIA. In normal pregnant women, serum hCG changed as pregnancy progressed, but serum free beta hCG was not detected at any time. In contrast, serum free beta hCG was measurable in the majority of patients with trophoblastic disease. Strong correlations were found between the concentration of free beta hCG and that of hCG in each type of trophoblastic diseases. The mean free beta hCG to hCG ratio was lowest for hydatidiform mole and highest for choriocarcinoma, and the difference between the ratios in these 2 groups was statistically significant. Serial measurements in 7 patients with trophoblastic disease failed to reveal remarkable changes in the free beta hCG to hCG ratio throughout their clinical course. We conclude that the production of free beta hCG increases with the immaturity of the trophoblastic cell, and the degree of differentiation of trophoblastic cells may be reflected by the free beta hCG to hCG ratio.

Histological origins of discordant chorionic gonadotropin secretion in malignancy.

Serum hCG, alpha hCG, and beta hCG levels were measured using monoclonal antibodies in women with trophoblastic disease (n = 138) and germ cell neoplasia (n = 123). Elevated serum beta hCG levels were present initially in the majority of the trophoblastic disease patients. By 12 weeks postevacuation raised serum beta hCG levels were detected in 42% of patients with malignant disease compared to 12% of patients with benign disease. No significant relationship was found between the initial alpha hCG levels and malignancy or resistance to chemotherapy. Increased serum free subunit levels did not distinguish between choriocarcinoma or benign hydatidiform moles, but increasing beta hCG to hCG ratios identified patients with high risk disease requiring multiagent chemotherapy. In nongestational malignancy, increased subunit levels occurred in fewer patients and to a lesser extent. Higher beta hCG and alpha hCG levels coincided with a histology of proliferating intermediate and cytotrophoblast cells, respectively, while high hCG levels occurred in association with syncytial proliferation. A histological mechanism for hCG synthesis is proposed, whereby mRNA for hCG subunits in syncytium depends on supplies of presynthesized mRNA introduced by fusion from differentiating cytotrophoblasts. Abnormalities in the extent and rate of differentiation would result in imbalanced subunit secretion.

Early pregnancy human chorionic gonadotropin (hCG) isoforms measured by an immunometric assay for choriocarcinoma-like hCG.

Human chorionic gonadotropin (hCG) exhibits molecular heterogeneity in both its protein and carbohydrate moieties. This communication describes changes in hCG isoforms detected directly in clinical samples. These isoforms, quantified in blood or urine specimens, show a progression of change throughout normal pregnancy. Early pregnancy produces a type of hCG that resembles, in terms of immunoreactivity, a major form of hCG excreted in choriocarcinoma. The isoforms predominate for the first 5-6 weeks of gestation and then diminish, being replaced with the hCG isoforms which predominate throughout the remainder of pregnancy. The alteration in hCG isoform content occurs in both blood and urine. The progression of isoforms is best delineated by calculating the change in the ratio of the two forms, as many hCG assays either do not detect or fail to discriminate among these isoforms. An analogous pattern of hCG isoforms was observed in patients with in vitro fertilization pregnancies. hCG isolated from the pituitary displayed binding characteristics similar to those of the hCG derived from normal pregnancy urine. The early pregnancy hCG isoforms appear to have a differential expression in normal pregnancy as opposed to pregnancies which will not carry to term, suggesting that a determination of the relative balance of hCG isoforms may have diagnostic application in predicting pregnancy outcome.

Epithelioid trophoblastic tumor: morphological and immunohistochemical study of three lung lesions.

Epithelioid trophoblastic tumor (ETT) is a term proposed for an unusual variant of trophoblastic tumor that is closely related to choriocarcinoma but shows monomorphic growth of highly atypical trophoblastic cells instead of the typical dimorphic pattern of choriocarcinoma. We report here 3 cases of ETT, all of which were lung lesions probably originating from uterine trophoblastic disease. The antecedent pregnancies of the 3 cases were hydatidiform mole, invasive mole, and term pregnancy, respectively. The tumors were composed of highly atypical mononucleate cells, which mainly involved alveolar spaces, forming nests with central eosinophilic necrosis. Multinucleate giant cells were found within the nests, but they were fewer in number than in typical choriocarcinoma. The tumors were not associated with extensive hemorrhage or necrosis, except for 1 case, in which the ETT was combined with typical dimorphic choriocarcinoma. Immunohistochemically, multinucleate giant cells and occasional mononucleate tumor cells showed positivity for human chorionic gonadotropin. Staining for human placental lactogen was positive in rare multinucleate giant cells, and in 1 case, tumor cells showed diffuse positivity for placental alkaline phosphatase. Because ETT has a remarkably epithelioid appearance in cytological and architectural features, differentiation from the epithelial malignancies is problematic. Trophoblastic markers are frequently expressed in nontrophoblastic tumors, and reactivity for those markers alone is not sufficient for exclusion of other tumors. Rather, evidence of ETT comes from a combination of morphological features, immunohistochemical study, and clinical history.

Mixed lymphocyte reaction in gestational trophoblastic disease: presence of a specific plasma inhibitor of the response to paternal alloantigens.

One-way wife-husband and wife-unrelated donor mixed lymphocyte reactions (MLR) were performed for 17 patients with malignant gestational trophoblastic disease (MGTD) and 17 normal pregnant subjects in the first trimester. The response of patients with MGTD to the husbands' lymphocytes did not differ significantly from the response to donors' lymphocytes when the MLR was performed in pooled human serum. Autologous plasma from patients with MGTD suppressed the MLR to husbands' lymphocytes but not that to donors' lymphocytes. Plasma from pregnant subjects in the first trimester did not suppress the wife-husband MLR. It is postulated that the specific plasma blocking activity may contribute to the failure to reject the trophoblastic tumours.

Serum 17 alpha-hydroxyprogesterone in patients with gestational trophoblastic neoplasms.

Serum 17alpha-hydroxprogesterone (17-OHP), progesterone (P), and human chorionic gonadotropin (hCG) levels were measured by specific radioimmunoassay in 19 patients undergoing laparoscopy or laparotomy with either unevacuated molar pregnancy or nonmetastatic gestational trophoblastic neoplasms (GTN), in 10 normal pregnant patients at equivalent gestational age (7-21 weeks), and in 4 patients with metastaic GTN following hysterectomy and bilateral salpingo-oophorectomy. All patients with theca lutein cysts had significantly elevated serum 17-OHP levels compared to those in 1) normal pregnancy, 2) patients with GTN and normal-size ovaries, 3) patients with metastatic GTN in the absence of ovaries (P less than 0.02). Levels of serum 17-OHP but not P correlated with the degree of ovarian enlargement (r = 0.87, P less than 0.05). Serum P concentrations in patients with theca lutein cysts, although higher than the levels in cases of GTN with normal-size ovaries, were not significantly different from the levels in normal pregnancy (P greater than 0.05). Serum hCG levels in patients with theca lutein cysts, though higher than the normal pregnancy levels (P less than 0.05), were not significantly different from those in cases of GTN with normal-size ovaries and GTN without ovaries (P greater than 0.05). Under the conditions studied, no correlation was observed between serum hCG and P levels in our cases of GTN. Increased serum 17-OHP level in a patient with GTN suggests the presence of theca lutein cysts.

Serum testosterone and dihydrotestosterone in patients with trophoblastic disease.

Serum testosterone (T) and dihydrotestosterone (DHT) were measured by radioimmunoassay in 14 patients with unaborted hydatidiform mole and in 16 patients with normal pregnancy of similar gestational age. Serum human chorionic gonadotropin (hCG) was measured by the radioreceptor assay in patients with hydatidiform mole. Serum T ranged from 0.27 to 5.39 ng/ml with a mean +/- SE of 2.21 +/- 0.45 ng/ml in patients with hydatidiform mole mole and from 0.20 to 2.40 ng/ml with a mean +/- SE of 0.80 +/- 0.14 ng/ml in patients with normal pregnancy, the difference being statistically significant (P = less than 0.005). Similarly, patients with molar pregnancies had a significantly higher (P = less than 0.005) serum DHT (range: 0.09 to 0.62 ng/ml; mean +/- SE: 0.29 +/- 0.05 ng/ml) than patients with normal pregnancies (range: 0.04 to 0.28 ng/ml; mean +/- SE 0.12 +/- 0.02 ng/ml). There was no significant correlation between uterine size or serum hCG and serum T or DHT. The possible sources of the elevated serum T and DHT and the lack of hirsutism or virilization in patients with trophoblastic disease are discussed.

Evaluation of prognostic factors and staging in gestational trophoblastic tumor.

OBJECTIVE: To evaluate factors influencing survival and compare current classification systems in women treated for malignant gestational trophoblastic tumor. METHODS: A consecutive series of 454 women treated between 1968-1992 was reviewed retrospectively to identify potential clinical prognostic factors using univariate analysis of life tables. All patients were evaluated using clinical classification, World Health Organization, and recently modified International Federation of Gynecology and Obstetrics (FIGO) staging systems, applied retrospectively. Multivariate Cox regression analysis was used to model potential independent prognostic factors within subsets of the patient population. RESULTS: Factors identified by univariate analysis as potential prognostic influences included age, duration of disease, type of antecedent pregnancy, clinicopathologic diagnosis, site of metastases, number of metastatic sites and foci, tumor size, and prior therapy. The pre-therapy hCG level was not significantly associated with survival (P < .04). Multivariate Cox modeling consistently identified prior therapy, type of antecedent pregnancy, number of metastatic sites, and duration of disease as independent prognostic factors. Clinicopathologic diagnosis and hCG level were of borderline significance only in some models of the total patient population. All classification systems were able to identify low- and high-risk subsets of patients with approximately equal efficiency. The addition of FIGO substages enhanced discrimination between prognostic groups in patients with stage III disease. CONCLUSIONS: Existing systems for the classification of malignant gestational trophoblastic tumor are based in part on factors that are not independently prognostic, such as hCG level or tumor size. These systems discriminate between low- and high-risk patients with approximately equal efficiency. The clinical classification system is currently preferred for determining initial therapy in women with malignant gestational trophoblastic tumors.

Use of an immunoradiometric assay and a radioimmunoassay for the detection of free beta-human chorionic gonadotropin.

An immunoradiometric assay and a radioimmunoassay (RIA) were used to quantitate human chorionic gonadotropin (hCG) in the sera of ten pregnant women at term and of six women with gestational trophoblastic neoplasia. The two techniques show good correlation (Pearson correlation coefficient .96) in the assay of pregnancy serum. Because only the RIA, and not the immunoradiometric assay, measures the free beta-subunit of hCG, a comparison of the results obtained by the two immunoassay methods permits a semi-quantitative assessment of the free beta-subunit. The numerical results may not reflect the actual concentration of free beta-subunit in that two different immunoassay methods are used.