Choriocarcinoma Research Articles

The prognosis of gestational trophoblastic neoplasia patient with residual lung tumor after completing treatment

Objective. To analyze retrospectively the prognosis of gestational trophoblastic neoplasia (GTN) patients who achieved normal β-hCG titer after completing treatment but remained with residual lung tumor. Method. A total of 1130 GTN patients were hospitalized at Peking Union Medical College Hospital from January 1985 to January 2004. Among these patients, 901 achieved complete remission (CR); 152 achieved normal blood β-hCG titer after the completion of treatment but remained with residual lung tumor (defined as partial remission). Retrospective analyses were carried out on the 152 patients. Statistical analysis was used to compare the recurrent rate of the CR patients with the progression rate of the 152 patients. Result. 17 of the 152 patients lost follow-up. Of the rest 135 patients followed up from 14 to 110 months, 83 showed no significant changes as to their residual tumors; 46 patients' residual tumors diminished or disappeared; and the other 6 patients got progression of disease (PD), with β-hCG level going up 6–8 months after completing treatment. There is no significant statistical difference ( P > 0.05) between the recurrent rate of the 901 CR patients and the progression rate of the 152 patients. There is also no significant statistical difference ( P > 0.05) between the recurrent rate of the CR patients with lung metastasis and the progression rate of the 152 patients. Conclusion. After achieving normal β-hCG titer, patients whose lung tumor stayed unchanged even following several additional courses of chemotherapy should be considered as CR patients. Follow-ups should be strictly carried out on these patients, especially at around 6 months after the completion of treatment, and particularly for high-risk and drug-resistant choriocarcinoma (CC) patients.

Ovarian nongestational choriocarcinoma mixed with various epithelial malignancies in association with endometriosis

Background Ovarian choriocarcinoma (CC) is rarely encountered as compared to uterine CC. Furthermore, ovarian CC coexisting with surface epithelial tumor is very rare. Case A 50-year-old postmenopausal woman, gravida 0, was admitted to our hospital with abdominal pain and distention due to a complex ovarian tumor. The laboratory data showed high serum level of CA125, neuron specific enolase (NSE), and hCG β-subunit C-terminal peptide (hCG-β-CTP). Total abdominal hysterectomy, right salpingoophorectomy, and lymph node dissection were performed. The right ovary revealed a cystic tumor with two solid parts: larger part, endometrioid adenocarcinoma and small cell carcinoma; smaller part, predominantly CC and focally clear cell adenocarcinoma. CA125 was rapidly decreased after first operation, but hCG-β-CTP levels repeated distinctive fluctuations and NSE abruptly increased during the last few months before death. The patient died 10 months after the first operation. Conclusion Only four cases of ovarian nongestational CC coexisting with surface epithelial tumor have been reported. This is the first reported case of admixture of CC with three epithelial malignancies. We assume that endometrioid and clear cell adenocarcinomas arose at different sites as tumorigenic factors in association with endometriosis, and the former may have been dedifferentiated into small cell carcinoma and the latter to CC. Coexistence of CC with small cell carcinoma is considered to be responsible for relative chemoresistance leading to poor prognosis.

A Case of Primary Choriocarcinoma of the Lung

A primary choriocarcinoma of the lung is extremely rare, and difficult to distinguish from a metastatic choriocarcinoma considering that the lung is also one of the most frequent site s of metastasis. We report a 28-year-old woman patient who was initially misdiagnosed with an ectopic pregnancy and was operated on under the impression of an unidentified malignancy of the lung, which was finally proven to be a chorio carcinoma of the lung. A pelvic examination by a gynecologist, pelvic magnetic resonance imaging and whole body fluorodeoxyglucose positron emission tomography-computed tomography was performed in order to rule out a metastatic choriocarcinoma of the lung. After a curative operation, her serum β-human chorionic gonadotropin (HCG) level, which was highly elevated in the initial evaluation, had decreased dramatically to the normal range. She is currently being followed up regularly without any evidence of recurrence or elevation of her β-HCG level. (Tuberc Respir Dis 2006; 61: 578-584)

Adrenal Choriocarcinoma with Spontaneous Rupture and Hemoperitoneum: Report of a Case

We present a case with an 8×8×4 cm tumor of the right adrenal gland, which was revealed by abdominal ultrasonography and computed tomography (CT). Hemoperitoneum with hypovolemic shock, due to the adrenal tumor rupture, occurred during the patient's hospitalization. Laparotomy was performed for hemostasis. The major bleeder was located in the perforation hole of the right adrenal tumor. The tumor and the right kidney were excised in toto and the pathology turned out to be choriocarcinoma. Adjuvant chemotherapy with etoposide, methotrexate, actinomycin-D, cyclophosphamide, and vincristine (EMA/CO) was given to the patient. There was no recurrence of choriocarcinoma one year after the operation and the patient's serum, β-hCG remained normal.

Gene expression-based classification of nonseminomatous male germ cell tumors

Male adult germ cell tumors (GCTs) comprise two major histologic groups: seminomas and nonseminomas. Nonseminomatous GCTs (NSGCTs) can be further divided into embryonal carcinoma (EC), teratoma (T), yolk sac tumor (YS), and choriocarcinoma (CC) on the basis of the lineage differentiation that they exhibit. NSGCTs frequently present as mixed tumors consisting of two or more histological subtypes, often limiting correlative studies of clinical and molecular features to histology. We sought to develop a molecular classifier that could predict the predominant histologic subtype within mixed NSGCT tumor samples. The expression profiles of 84 NSGCTs (42 pure and 42 mixed) and normal age-matched testes were obtained using Affymetrix microarrays. Using prediction analysis for microarrays, we identified 146 transcripts that classified the histology of pure NSGCTs samples with 93% accuracy. When applied to mixed NSGCTs, the classifier predicted a histology that was consistent with one of the reported components in 93% of cases. Among the predictive transcripts were CGB (high in CC), LCN2 (high in T), BMP2 (high in YS), and POU5F1 (high in EC). Thus, the expression-based classifier accurately assigned a single predominant histology to mixed NSGCTs, and identified transcripts differentially expressed between histologic components with relevance to NSGCT differentiation.

The role of KiSS-1 and matrix metalloproteinase-9 in regulation of invasion of trophoblasts

To explore the role of metastasis-related gene KiSS-1 and matrix metalloproteinase (MMP)-9 in regulation of invasion of trophoblasts. RT-PCR and Western blotting were used to detect the MMP-9 and KiSS-1 expression levels in the placental tissues obtained from 90 cases of normal pregnant women undergoing artificial abortion, induction of labor with water bag or selective cesarean section among which 30 cases were in the first trimester, 30 in second-trimester and 30 cases of term pregnancy, and in the placental tissues of 40 cases of preeclampsia (15 cases of mild and 25 cases of severe preeclampsia) undergoing cesarean section, and tissues of 90 cases of hydatidiform mole, 9 cases of invasive mole and 8 cases of choriocarcinoma, all undergoing surgery. The expression levels of MMP-9 mRNA and protein were higher in first-trimester [A value 0.391 +/- 0.215, (36 +/- 7) microg/100 microg total protein] and then decreased gradually with the progress of gestation. The expression levels of MMP-9mRNA and protein in the term placental samples were significantly lower than those of first-trimester (both P < 0.01). The expression levels of KiSS-1mRNA and metastin in normal placenta increased along with the progress of gestation (both P < 0.01). The KISS-1 mRNA expression level and MMP-9 protein expression level in the placental tissue of preeclampsia were 0.09 +/- 0.06 (A value) and (9.6 +/- 4.3) microg/100 microg total protein respectively, both significantly lower than those of the term placenta (both P < 0.01). The expression levels of MMP-9 mRNA and protein in the tissues of gestational trophoblastic disease were significantly higher than those in the first-trimester placenta (both P < 0.01). The expression level of KISS-1 mRNA and metastin in the tissues of hyddatidiform mole and invasive mole were both significantly lower than those in the first trimester placenta (P < 0.05, P < 0.01). The expression of KiSS-1mRNA and metastin in the tissues of choriocarcinoma could not be detected. The expression of the invasion-related gene, MMP-9, is positively related with, while the invasion suppressor gene, KiSS-1, is negatively related with the invasive ability of trophoblasts. The interaction of these two genes plays an important role in regulation of the invasion of trophoblasts.

Expression pattern of the AP-1 family of transcription factors in Gestational Trophoblastic Diseases (GTD)

The human placenta is an endocrine tissue with a unique capacity for rapid, but tightly controlled proliferation and invasion. Gestational trophoblastic diseases (GTD) are placental pathologies with endocrine activity and partially malignant potential and include hydatidiform moles (HM), placental site nodules (PSN) and tumors such as placental site trophobastic tuor (PSTT) and choriocarcinomas (CC). The AP-1 family of transcription factors (activating protein-1) is composed of the cellular homologs of the Jun and Fos oncoproteins, immediately involved in cellular proliferation, differentiation and invasion processes as well as in the regulation of endocrine genes. We have recently described the expression pattern of the AP-1 factors in the normal human placenta. Their systematic expression in GTD has not been studied so far. For this reason in the present study we investigated the expression pattern of AP-1 family in GTD and compared it to the expression in normal placenta by using immunohistochemistry with specific polyclonal antibodies against all members of the AP-1 family (JunB, JunD, c-Jun, c-Fos, FosB, Fra1, Fra2). Immunohistochemistry was performed on nomal human placentas (positive control) and on 20 cases of GTD including four choriocarcinomas, one PSTT, one PSN and fourteen hydatidiform moles. In the normal placenta and in hydatidiform molar samples most AP-1 factors (especially c-Jun, JunD and Fra2) were expressed in the intermediate (extravillous) trophoblast. In addition, in molar lesions strong expression was found in trophoblast proliferating from the surface of villi. There was only weak expression of JunB and Fra2 in small fractions of villous cyto- and sycytiotrophoblast nuclei. In choriocarcinomas, PSN and especially in PSTT there was a strong expression for c-Jun, JunD, Fra1 and Fra2. The specific localization to extravillous trophoblast and their expression pattern in GTD indicates that the AP-1 family of transcription factors is probably implicated in regulating proliferation and invasion of trophoblast.

Gestational trophoblastic tumors in Norway, 1968-1997: patient characteristics, treatment, and prognosis.

The aim of this study was to give an overview of the Norwegian population of gestational trophoblastic tumors (GTT), diagnosed during 1968-1997 and treated with chemotherapy at the Norwegian Radium Hospital (NRH), with regard to patient characteristics, treatment, and prognosis. The cases were grouped according to a modified version of the WHO scoring system. Staging was performed retrospectively according to the systems adopted by FIGO. Survival estimates were calculated by the method described by Kaplan and Meier. Cox regression models were used to find the best classification system with regard to prognosis (disease-free survival). A total of 141 cases, 106 invasive moles (IM) and 35 choriocarcinomas (CC), were diagnosed in Norway and treated with chemotherapy at the NRH in the period 1968-1997. Altogether, 56% of the patients were assigned to the low-risk category, 20% to the medium-risk category, and 15% to the high-risk category. Most cases were classified into the clinical stages I (69%) and III (23%). The overall 5-year survival rate was 96%. A more favorable prognosis was seen in patients diagnosed in the 1980s and 1990s compared with those diagnosed in the 1970s (P = 0.04). Five patients had progressive disease and died from the disease. Nine patients relapsed. The prognosis (disease-free survival) was more favorable for IM compared with CC (P < 0.01). The FIGO classification system seemed to be a better predictor of disease-free survival than the WHO scoring system. This study showed that the prognosis of patients with GTT improved in the 1980s and 1990s in Norway, and that the FIGO system might be the best predictor of disease-free survival.

Human chorionic gonadotrophin reduces matrix metalloproteinases expression in JEG-3 choriocarcinoma cell line

Objective To uncover the effect of human chorionic gonadotrophin (hCG) on the invasion of choriocarcinoma cells.Methods The effect of hCG on the expression of matrix metalloproteinases (MMPs) in JEG\|3 choriocarcinoma cell line was investigated by applying the method of reverse transcription polymerase chain reaction (RT\|PCR). Results The results showed that, among the 18 types of MMPs only MMP\|8,\|10, \|12,\|19 were found to be expressed by JEG\|3 cells. After the incubation with 25 IU/ml hCG for 50hours, the expression of these 4 types of MMPs were all significantly reduced. Conclusion The invasiveness of JEG\|3 choriocarcinoma cell line was associated with the expression of MMP\|8, \|10, \|12, \|19, high levels of hCG could reduce the invasion of choriocarcinoma cells by inhibiting MMPs expression.

Choriocarcinoma cells modulate the cytokine production of decidual large granular lymphocytes in coculture.

How do major histocompatibility complex (MHC) I positive/negative choriocarcinoma (CC) cells affect the production of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-10 (IL-10), interleukin-4 (IL-4), and granulocyte-macrophage colony-stimulating factor (GM-CSF) by decidual CD56++ cells (large granular lymphocytes [LGL]), LGL-depleted decidual cells (WASH) and unseparated decidual cells (DEC) in cocultures? Decidual tissue was obtained by legal abortions. CD 56++ LGL were isolated in a magnetic cell separator. Cytokines were measured by ELISA. Differences were analyzed for significance by Wilcoxons test. We found a significant increase of IL-10 in LGL/JEG-3 and of TNF-alpha in LGL/JAR cocultures compared to noncocultured decidual cells. There was a significant increase of IL-10 and TNF-alpha and a significant decrease of GM-CSF in WASH and DEC cocultures with both JEG-3 and JAR. IFN-gamma was only found in 3/11 cases of LGL/JAR cocultures. No IL-4 was found in any experiment. MHC class I positive/negative CC modulate the cytokine production of decidual LGL in different ways.

Trophoblastic neoplasia—A Workshop Report

Gestational trophoblastic disease (GTD) represents a unique spectrum of disease that includes hydatidiform moles (HM) [complete, partial (PM) and invasive moles (IM)], choriocarcinoma (CC), persistent trophoblastic disease (PTD) and placental site trophoblastic tumour (PSTT). Different histopathological entities, biochemical features and cytogenetic status can define these diseases. These issues were the topics of the workshop on GTD, which was conducted by Hiroaki Soma (Saitama, Japan) and Brent Dubeshter (Rochester, New York). Most of the information available concerning the epidemiology of GTD continues to be poorly understood, because until now, geographical variations in the incidence of GTD only were being reported. For example, most reports of HM in developing countries come from data based in individual hospitals. Therefore, little information is available to account for the differences in the incidence of GTD in different countries and regions. Since the setting up of the Trophoblastic Disease Committee by the Japan Society of Obstetrics and Gynecology in 1956, the Committee has gradually made progress in promoting research on this disease. Registration records for GTD patients in every district have been collected annually in Japan since 1974 and have been based upon the population statistics. In the Introduction, presented by Hiroaki Soma, recent trends reflecting the incidence of antecedent pregnancies in choriocarcinoma patients registered from 1994 to 1997 collated by the Trophoblastic Disease Committee in Japan, demonstrated dramatic changes. The percentage of antecedent pregnancy for choriocarcinoma was preceded not by hydatidiform moles (16 per cent), but by normal birth (42 per cent), because of a significant decrease in the reported number of patients with hydatidiform moles in Japan. In comparison, a large number of hydatidiform moles have occurred in South Vietnam, which was associated with the war. In contrast, although the epidemiology of gestational trophoblastic disease in Himalayan mountain people is still unknown, an incidence of gestational trophoblastic disease in Nepal, based on reports from two hospitals, ranged from 2.64 to 7.07 per 1000 pregnancies and from 3.02 to 8.4 per 1000 deliveries. To date, there has been a considerable difference in the management of gestational trophoblastic disease between

False-Positive Human Chorionic Gonadotropin Levels

Choriocarcinoma is a rare but curable malignancy. Diagnosis depends on serum human chorionic gonadotropin (hCG) levels. Occasionally, elevated serum hCG levels can persist when a woman does not have choriocarcinoma, putting such women at risk for needless treatment. These authors studied 12 …

Detection of the alpha-subunit of inhibin in trophoblastic neoplasia

Placental trophoblasts are the primary source of serum inhibin during pregnancy. We sought to characterize inhibin immunolabeling in trophoblastic neoplasms and compare the results with those for established markers of trophoblastic differentiation. Formalin-fixed, paraffin-embedded tissues from three normal term placentas, 13 hydatidiform moles (HM), five choriocarcinomas (CC) (three gestational, one testicular, one mediastinal), and five placental site trophoblastic tumors (PSTT) were immunolabeled with antibodies to the alpha-subunit of inhibin, hPL, and β-hCG. Additionally, six firsttrimester placentas were immunolabeled with antibody to inhibin alone. Trophoblastic subpopulations were assessed for the number of positive cells (1% to 24% = 1+, 25% to 49% = 2+,50% to 74% = 3+, 75% to 100% = 4+). Immunolabeling in term placenta and HM was similar, because β-hCG was the most sensitive marker (4+) of syncytiotrophoblasts followed by inhibin (3–4+) and hPL (2–3+). Immunolabeling of syncytiotrophoblasts in CC was similar to that in term placenta and HM, except for negative hPL staining in two cases. In HM, inhibin labeling of intermediate trophoblasts (2–3+) was less than that for hPL (3–4+). In CC, inhibin and hPL labeling of intermediate trophoblasts was more variable with negative hPL reactivity in two cases. Inhibin and hPL did not stain cytotrophoblasts. In PSTT, inhibin immunolabeling was a better marker than hPL in two cases, inferior in two, and similar in one. Inhibin labeling of syncytiotrophoblasts was less than that for β-hCG, but did not have the often marked background staining that was present with β-hCG. Immunolabeling of trophoblast subpopulations for inhibin was similar between first-trimester placenta, term placenta, and HM. We conclude that inhibin is a useful immunohistochemical marker of trophoblastic neoplasia and should be included in the antibody panel with β-hCG and hPL.

Expression of CDKI P27 Kip1 in malignant and non-malignant trophoblastic cells

Summary The cyclin-dependent kinase inhibitors (CDKIs) inhibit the kinase activities of the cyclin and CDK complexes and block transitions of the cell cycle. As a negative regulator of the cell cycle, CDKI P27 kip1 regulates the decision of cell cycle to enter into S-phase or arrested in G1-phase by blocking G1 cyclin dependent kinase activities. Evidence suggests that P27 kip1 may be involved in tumorigenesis and acts as a tumor suppressor gene. In this study, the expression of P27 kip1 in complete hydatidiform mole (CHM), invasive mole (IM) and choriocarcinoma (CC) was investigated as well as in normal chorionic villi by immunohistochemistry. Decreased expression of P27 kip1 was observed in malignant trophoblastic neoplasms with a positive rate of 21.43%, which is less than that in normal chorionic villi (80%) and in CHM (73.33%) (P kip1 in those CHMs with large uterus size for gestational date was lower than that in those with a normal or small uterus for date (42.86% vs 100%). (P kip1 may be involved in the tumorigenesis of gestational trophoblastic neoplasm as a negative regulator of cell cycle, and the expression level of P27 kip1 in trophoblastic cells may be a prognostic factor for CHM.

The differential diagnosis of choriocarcinoma and placental site tumour

Choriocarcinoma (CH), the first human neoplasm to be monitored by a tumour marker and cured by chemotherapy, presents unique diagnostic problems because of its rarity and because criteria used to define malignancy in other neoplasms, such as vascular invasion, cellular pleomorphism, mitoses and even metastases, are intrinsic features of normal trophoblast. In no other neoplasm is the context in which trophoblast is found as important or more important than its appearance. It follows that clinico-pathological correlation is essential. Finding abundant pleomorphic trophoblast after a complete mole (CM), often means persistence of the mole with no chorionic willi in the sample, but finding abundant pleomorphic trophoblast after a normal term pregnancy is almost certainly due to CH or to a new pregnancy. Placental site trophoblastic tumour (PSTT) is a chenoresistant form of trophoblastic tumour with less tendency for vascular invasion or metastases but, in most cases, only curable if it can be eradicated by surgery. CH and PSTT look different and behave in different ways, but in some cases they merge into each other. The main diagnostic problems encountered are: firstly, the differentiation of CH and PSTT from the abundant trophoblast, usually seen in early gestation; secondly, the differentiation of CH and PSTT from persistent trophoblast after a molar or non molar pregnancy; thirdly, the differentiation between CH with a predominantly cytotrophoblastic component and PSTT; and fourthly, the differentiation between CH, PSTT and trophoblastic metaplasia in non-gestational carcinomas.

Forty-five year's experience of the treatment of choriocarcinoma and invasive mole

Our work was begun in 1949, through many yera's effort, several chemicals (such as 6 MP, 5 FU and others) were found to be effective for the treatment of choriocarcinoma (C.C.) and invasive mole (I.M.). From 1959 through 1985, 1500 patients were consecutively treated. The mortality rate of CC was reduced from > 90% to < 20%. No more death occurred in IM. All Survivors followed up for 10–38 years showed no evidence of residual disease. 80% of the young patients treated with chemotherapy alone conceived after recovery. The pregnancy outcome showed no deviation from that of the general population. All children are growing up normally many married and gave birth to normal third generations. The results indicated that chemotherapy with 5 FU achieves not only a complete remission, but also a cure, even with wide-spread metastases. The results of choriocarinoma and invasive mole treated with mainly 5 FU were reported. The clinical experience in the management of metastases at different sites were also summarized.

947 - Treatment of resistant choriocarcinoma of the uterus

947 - Treatment of resistant choriocarcinoma of the uterus

Primary germ cell tumors of the mediastinum

Yolk sac tumor (YST), embryonal carcinoma (EC), choriocarcinoma (CC), and combined germ cell tumors (CGCTs) of the mediastinum are uncommon neoplasms. Only sporadic cases have been documented in the literature; therefore, the clinical behavior of these tumors when located in the mediastinum remains relatively unknown. The clinical and pathologic features of 64 cases of primary YST, EC, CC, and CGCTs without teratomatous components were reviewed. The immunohistochemical findings in 29 cases were also analyzed using a panel of monoclonal and polyclonal antibodies in formalin fixed, paraffin embedded tissues. The patients were all men between the ages of 14 and 63 years (mean, 38.5 years). Their clinical symptoms included chest pain, shortness of breath, chills, fever, and superior vena cava syndrome. None of the patients had a previous history of testicular neoplasm or tumor elsewhere. Macroscopically, the lesions in 27 patients were described as large, soft, hemorrhagic, and in some cases necrotic, and varied in greatest dimension from 6 to 20 cm. Histologically, the tumors displayed morphologic features similar to those of their gonadal counterparts. Pure YSTs accounted for the majority of cases in this series (38 of 64, 60%), followed by pure CCs (8 of 64, 12%) and pure ECs (6 of 64, 9%). CGCTs accounted for only 18% of the total cases (12 of 64). YSTs showed a variety of growth patterns; however, the reticular pattern was the most commonly observed. ECs showed a more solid growth pattern with marked pleomorphism of the tumor cells and abundant areas of necrosis. CCs were characterized by the presence of cytotrophoblastic and syncytiotrophoblastic elements with frequent areas of necrosis and hemorrhage. The cases of nonteratomatous CGCT consisted of 5 cases of EC + YST, 2 cases of EC + seminoma, 4 cases of YST + seminoma, and 1 case of EC + CC. In clinical staging, 14 patients were Stage I, 6 were Stage II, and 19 were Stage III. Information on follow-up ranging from 1 month to 13 years was available for 40 patients. Seventeen patients with YST died of their tumors. Of these, 10 who presented with Stage III disease died within the first 2 years. Unfortunately, no clinical staging was obtained for the other 7 patients in this group, and they died within 6-36 months. It is noteworthy that 4 patients with YST have survived for more than 2 years; these patients presented in Stages I and II, and 2 of them received aggressive therapy with chemotherapeutic agents and radiation. Two patients with Stage III EC died within 2 years. The remaining 4 patients with EC were lost to follow-up. Eight patients with CC died within 6 months after initial diagnosis; 7 of them presented Stage III disease and only 1 presented with Stage I. In the nonteratomatous CGCT category, 2 patients with EC + YST died within 2 years after initial diagnosis, whereas 3 patients with YST + seminoma were alive after 4-9 years. The results of this study confirm the aggressive nature of primary nonseminomatous germ cell tumor of the mediastinum; 72% of the patients with adequate follow-up died of their tumors within 6-36 months after diagnosis, despite aggressive therapy. Clinical and pathologic staging of mediastinal YST, EC, and CGCT are important parameters that may be helpful in predicting the clinical outcomes of patients with these tumors. The authors' findings suggest that the majority of tumors that are not limited to the mediastinum at the time of diagnosis have more aggressive behavior. On the other hand, mediastinal choriocarcinomas appeared to follow a very aggressive clinical course, regardless of treatment modality or clinical tumor stage.

P53 expression and tumor proliferative activity in testicular germ-cell tumors

We evaluated p53 expression and tumor proliferative activity (TPA) using monoclonal antibodies to Ki-67 and proliferating cell nuclear antigen (PCNA) in 26 patients with seminomatous and nonseminomatous testicular germ-cell tumors (GCTs). Correlation between p53 expression and TPA, as well as the clinical correlation with the expression of these proteins were also assessed. There were eight cases of pure seminoma and 18 cases of nonseminomatous GCTs, collectively consisting of 45 tumors or tumor components. The nonseminomatous GCTs were mixed or pure and included choriocarcinoma (CC), embryonal carcinoma (EC), immature teratoma (IMT), mature teratoma (MT), seminoma, and yolk sac tumor (YST). The ages of the patients with seminomatous GCTs ranged from 24 to 47 years (mean, 34 years) and those for patients with nonseminomatous GCTs ranged from 17 to 43 years (mean, 29 years). Sixteen (44%) of the 36 nonseminomatous GCTs or tumor components were positive for p53 protein. Ten (91%) of eleven ECs, three (38%) of eight YSTs, two (20%) of ten MTs, and the single case of CC were positive for p53 protein. All nine seminomas and three of six IMTs were only focally positive for p53 protein. The p53 expression in ECs and YSTs was significantly higher than that in IMTs, MTs, and seminomas (P=0.0001). TPA was present in the majority of the seminomatous and nonseminomatous GCTs, and was significantly higher in ECs and YSTs than in seminomas, MTs, and IMTs (Ki-67, P=0.0001; PCNA, P=0.0006). In the majority of the cases PCNA expression was higher than Ki-67 expression (P=0.0001). The mean TPA percentage was significantly higher in the p53-positive tumors or tumor components (EC and YST) when compared with the mean TPA percentage in those neoplasms that were focally positive or negative for p53 protein (Ki-67, P=0.003; PCNA, P=0.046). p53 expression was also associated with histologically aggressive tumors (ECs and YSTs) that also exhibit high TPA. No relationship appears to exist between the three tumor markers and the clinical stage or the patients' follow-up and outcome in this small series. Further studies are necessary to elucidate the roles of p53 and proliferation markers in testicular tumorigenesis and as prognostic markers.

509 Pregnancy after successful treatment of gestational trophoblastic disease (GTD)

Although GTD is uncommon, it is extremely important because of the high degree of curability with adapted treatment. It is becoming important to preserve young patients (pts) fertility. We reviewed the productive history ofall pts who received chemotherapy (CT) for a GTD at ISA, between January 1982 and December 1993. Only 34 pts had subsequent pregnancies: 19 had molar pregnancies (MP) and 15 choriocarcinomas (CC). The mean age was 27 years (range 17–38). Pts with CC received a combined regimen of CT with Vincristin and Methotrexate 9 pts and Etoposide and Actinomycin 6 pts. All those with MP were treated by a CT associating (Methotrexate and Vincristin). All of them entered a complete remission, 7 after a salvage CT. MP n = 15 CC n = 19 Number of pregnancies 28 29 Normal term pregnancies 18 23 Spontaneous abortion 3 1 Ectopic pregnancy 0 1 Placenta Acreta 0 0 Premature birth 1 1 Congenital malformations 3 3 Conclusion It is actually important to achieve 2 objectives in treating pts with GTD: first to cure them, second to preserve their fertility.