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Trophoblast-derived interleukin-6 (IL-6) regulates human chorionic gonadotropin release through IL-6 receptor on human trophoblasts.

We examined the capacity of trophoblast-derived interleukin-6 (IL-6) to stimulate secretion of placental hormones, including hCG. IL-6 stimulated hCG secretion by trophoblasts to a level similar to that stimulated by a GnRH analog. The analog, however, released hCG by an IL-6-independent mechanism because PM-1, a monoclonal antibody specific for IL-6 receptors (R), failed to block GnRH-mediated responses, but completely blocked IL-6-mediated hCG secretion, suggesting the existence of two distinct regulatory pathways for hCG release. Immunohistochemical analysis with another IL-6-R-specific antibody, MT-18, showed that IL-6-R was located only on the trophoblast layer of the placenta. Our data revealed the existence of a local regulatory network by which trophoblast-derived IL-6 interacts with IL-6-R on the trophoblasts, resulting in hCG release. Thus, two different regulatory networks, an IL-6 and IL-6-R system and a GnRH and GnRH-R system, regulate hCG release by human trophoblasts independently.

Antibodies, Monoclonal↗

Trophoblast-derived transforming growth factor-beta 1 suppresses cytokine-induced, but not gonadotropin-releasing hormone-induced, release of human chorionic gonadotropin by normal human trophoblasts.

Using a transforming growth factor-beta (TGF beta)-sensitive cell line, Mv1Lu (or CCL 64), we demonstrated that trophoblasts predominantly produced a latent form of TGF beta. After converting latent TGF beta to active TGF beta in vitro by acid (pH 2.5), alkali (pH 10.0), or heat (90 C; 10 min) treatment, addition of rabbit anti-TGF beta 1 antiserum resulted in the elimination of TGF beta activity, thus suggesting that trophoblasts produced at least a certain amount of latent TGF beta 1. To investigate the role of TGF beta 1 in placental hormonogenesis, we first studied the effect of recombinant (r) TGF beta 1 on the production of interleukin-6 (IL-6) and hCG by trophoblasts. rTGF beta 1 exerted no inhibitory activity on IL-6 and hCG production. The effect of rTGF beta 1 on cytokine-induced IL-6 and hCG release was then examined. While rTGF beta 1 failed to inhibit basal hCG secretion, it did inhibit recombinant tumor necrosis factor-alpha (rTNF alpha)-induced IL-6 release as well as rTNF alpha- and rIL-6-induced hCG release in a dose-dependent manner. However, rIL-1 alpha-induced IL-6 and hCG release was remarkably sensitive to rTGF beta 1-mediated suppression. In contrast, GnRH-induced hCG release, the response of which is independent of the IL-6 and IL-6 receptor system in trophoblasts, was completely resistant to rTGF beta 1. Thus, trophoblast-derived TGF beta 1 is an important regulatory molecule of cytokine-dependent, but not cytokine-independent, hCG release, possibly by converting latent TGF beta to active TGF beta at the local site of trophoblasts.

Chorionic Gonadotropin↗

Interleukin-10 modifies the effects of interleukin-1beta and tumor necrosis factor-alpha on the activity and expression of prostaglandin H synthase-2 and the NAD+-dependent 15-hydroxyprostaglandin dehydrogenase in cultured term human villous trophoblast and chorion trophoblast cells.

The concentrations of tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta), two inflammatory cytokines in amniotic fluid, have been shown to rise during chorioamnionitis. This is probably related to activation of the immune system in order to intensify the inflammatory process and to protect the maternal and fetal organism from infectious agents. These cytokines activate the PG biosynthetic pathway in several tissues, but few studies have examined effects on PG-metabolizing enzymes. When PGs are produced by increased synthesis and/or decreased metabolism at the chorio-decidual interface, labor can be induced. Interleukin-10 (IL-10) is known to act as an antiinflammatory cytokine. The goals of this study were to evaluate the interaction of IL-10 with IL-1beta and TNFalpha on PG synthesis and to determine the effects of IL-10, IL-1beta, and TNFalpha on PG metabolism using purified cultures of villous trophoblast and chorion trophoblast cells prepared from placentas of patients at term. Cells were treated with IL-1beta and TNFalpha with or without IL-10 for various times up to 24 h. Levels of messenger ribonucleic acid (mRNA) encoding PGH synthase-2 (PGHS-2) and NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) were quantified by Northern blotting, and PGE2 and 13,14-dihydro-15-keto-PGF2alpha (PGFM) output in the medium was measured by RIA. IL-1beta increased PGHS-2 mRNA and PGE2 output from villous and chorion trophoblasts and decreased PGDH mRNA in villous trophoblasts (all P < 0.05). These effects were reversed by IL-10. We found no change in PGHS-2 mRNA or PGE2 output in either trophoblast type treated with TNFalpha, but TNFalpha reduced PGDH mRNA in villous trophoblast, and this effect was reversed by IL-10 (both P < 0.05). We conclude that proinflammatory cytokines can influence PG output through effects on PG synthesis and metabolism and that these effects may be opposed by an antiinflammatory cytokine. These interactions may be important in the progression of preterm labor with underlying infection and in term labor in regions of the uterus where cytokine production is increased.

Cells, Cultured↗

Molecular heterogeneity of hCGbeta--related glycoproteins and the clinical relevance in trophoblastic and non-trophoblastic tumors.

We analyzed immunoreactive hCG/hCGbeta (IR-beta) in the sera and urine of patients with trophoblastic diseases and non-trophoblastic tumors by using enzyme immunoassays (EIAs) specific for intact hCG, free hCG beta, and beta-core fragment of hCG (beta-CF). In trophoblastic diseases, while intact hCG and free hCGbeta were contained in both serum and urine, the beta-CF could be detected only in the urine of the patients. The relative contribution of the beta-CF to the total urinary IR-beta accounted for about 30-50% in normal early pregnancy and hydatidiform mole, and more than 60% in choriocarcinoma. We conclude that intact hCG should be measured in the serum rather than in the urine as a tumor marker for trophoblastic diseases, and suggested that the ratios of intact hCG, free hCGbeta, and beta-CF to each other may be useful indices in the differential diagnosis of trophoblastic diseases. Ectopic IR-beta was also investigated in the sera and urine of the patients with cervical, endometrial, ovarian, lung, and bladder carcinomas. We found that even when IR-beta could not be detected in the serum, the urine of the same patients with cancer often contained the significant amounts of IR-beta. The chromatographic study indicated that these urinary IR-beta were essentially attributed to beta-CF, leading to the evaluation of urinary beta-CF as a tumor marker. The positive rated of urinary beta-CF were 48% for cervical, 38% for endometrial, and 84% for ovarian, 40% for lung, and 42% for bladder carcinomas. We conclude that ectopic production of hCG beta by non-trophoblastic tumors is not a rare phenomenon and it can be recognized as a tumor marker when beta -CF is measured in urine of the patients.

Antibodies, Monoclonal↗

Placental site trophoblastic tumor: with features between an exaggerated placental site reaction and a placental site trophoblastic tumor.

Chorionic villi, whose presence in cases of trophoblastic disease is normally used to exclude both a choriocarcinoma and placental site trophoblastic tumor (PSTT), were present in the initial uterine curettage specimen of a trophoblastic tumor. The lesion shared morphologic features of both an exaggerated placental site reaction and a PSTT. There was infiltration of the posterior wall of the uterus by small clusters and isolated cells which had a prominent affinity for vessels and resembled a usual placental bed reaction. There was, however, deep involvement of myometrium with extension to the cervix, and the condition persisted for 5 months after uterine evacuation. Because different treatment is entailed, identification of this lesion as a tumor of nonvillous trophoblast is also of great importance in a region where the more usual forms of trophoblastic disease represent a declining but not infrequent event. When products of gestation are examined, the possibility of a PSTT should be considered and the clinician alerted if there is a suggestion of excessive intermediate trophoblastic activity, regardless of the presence of chorionic villi. While this may result in the unnecessary followup of some cases, it would permit, with the aid of serial beta-hCG and HPL levels, the earlier detection of PSTTs.

Adult↗

Malignant trophoblastic tumors: immunohistochemical and flow cytometric comparison of choriocarcinoma and placental site trophoblastic tumors.

We performed an immunohistochemical and flow cytometric study of the formalin-fixed, paraffin-embedded tissues of eight recent gestational choriocarcinomas (CCs) and three placental-site trophoblastic tumors (PSTTs). The follow-up period ranged from 1 to 144 months (mean, 74.3 months). In the CCs, which consisted predominantly of cytotrophoblasts and syncytiotrophoblasts intermingled with small amounts of intermediate trophoblasts, cytotrophoblasts were occasionally positive for beta-subunit human chorionic gonadotropin (HCG) and syncytiotrophoblasts contained abundant HCG. Some intermediate trophoblasts were positive for HCG and many were positive for human placental lactogen. In the three PSTTs, which were characterized by a monomorphic proliferation of intermediate trophoblasts, the tumor cells were positive for human placental lactogen and placental alkaline phosphatase. The tumors of two patients, including one fatal case, contained more human placental lactogen-positive cells than HCG-positive cells, while the tumor of the remaining patient, who had high serum HCG levels, showed a reversed staining pattern resembling that of CC; this patient has been alive without disease for 9 years. One CC patient and one PSTT patient died of multiple lung metastases, despite hysterectomy and multiagent chemotherapy. All CCs and PSTTs had an exclusively diploid DNA content, and there was no correlation among histopathologic and immunohistochemical features, DNA ploidy, S-phase fraction, and clinical outcome for patients with these tumors. These results suggest that there is a PSTT that immunohistochemically resembles CC and that flow cytometric and immunohistochemical analysis may not be effective tools to predict the biologic behavior of malignant trophoblastic tumors.

Adult↗

Trophoblastic tumors of the testis other than classic choriocarcinoma: "monophasic" choriocarcinoma and placental site trophoblastic tumor: a report of two cases.

We report two unusual forms of testicular trophoblastic tumor. One was a mixed germ cell tumor in a 19-year-old man that had a predominant component of nodules of cytotrophoblast cells with only rare syncytiotrophoblast cells. These nodules of "monophasic" choriocarcinoma were diffusely positive for human chorionic gonadotropin (hCG), which stained the syncytiotrophoblast cells more intensely; stains for human placental lactogen (HPL) highlighted only the latter cells. The second tumor occurred in a 16-month-old boy. It consisted of a pure proliferation of intermediate trophoblast cells and was identical to the placental site trophoblastic tumor of the uterus. The tumor cells showed diffuse immunoreactivity for HPL and patchy staining for hCG. Despite the occurrence of vascular wall invasion, the patient was alive and well at 8 years follow-up with no treatment other than orchiectomy. These cases show that trophoblastic tumors other than classic choriocarcinoma occur rarely in the testis. The differential diagnosis of the "monophasic" choriocarcinoma included seminoma and the solid variant of yolk sac tumor, but the tumor had larger, more irregular nuclei than those of seminoma and was not associated with distinctive yolk sac tumor patterns. The placental site trophoblastic tumor may be confused with Leydig cell tumor or choriocarcinoma, but awareness of its occurrence in the testis and the immunohistochemical findings should permit its recognition.

Adult↗

Placentation in the degu (Octodon degus): analogies with extrasubplacental trophoblast and human extravillous trophoblast.

This study examined the placentation in the degu, the origin of the extrasubplacental trophoblast (EST) (extravillous trophoblast in human), and the activity of Na+/K+ ATPase in the placental barrier during different gestational ages, as part of a wider effort to understand the reproductive biology of this species. Fifteen degus at the first stage of gestation, midgestation and at term of pregnancy were studied. At day 27 of gestation, the subplacenta is formed under the wall of the central excavation. Simultaneously, the outermost trophoblast of the ectoplacental cone differentiated into secondary trophoblast giant cells that lie on the outside of the placenta, forming an interface with the maternal cells in the decidua. These giant cells immunostained positive for cytokeratin (CK) and placental lactogen (hPL) until term. During this period, the EST merged from the subplacenta to the decidua and immunostained negative for CK, but at term, immunostained for CK and hPL in the maternal vessels. The vascular mesenchyme of the central excavation invaded the chorioallantoic placenta during this period, forming two fetal lobules of labyrinthine-fine syncytium, the zone of the placental barrier. The activity of Na+/K+ ATPase in the placental barrier was constant during the gestational period. The residual syncytium at the periphery of the placental disc and between the lobules was not invaded by fetal mesenchyme and formed the marginal and interlobular labyrinthine syncytium that immunostained first for CK, and later for hPL, as in the labyrinthine fine syncytium. The presence of intracytoplasmic electron-dense material in the interlobular labyrinthine syncytium suggested a secretory process in these cells that are bathed in maternal blood. Placentas obtained from vaginal births presented a large, single lobe, absence of the subplacenta, and a reduced interlobular labyrinthine syncytium. At day 27, the inverted visceral yolk sac is observed and its columnar epithelium immunostained for CK and hPL. This suggests that the yolk sac is an early secretory organ. The epithelium of the parietal yolk sac covers the placenta. The origin of the EST in the degu placenta and its migration to maternal vessels allows us to present this animal model for the study of pregnancy pathologies related to alterations in the migration of the extravillous trophoblast.

Animals↗

Fibroblast growth factor (FGF)-1, FGF2, FGF7 and FGF receptors are uniformly expressed in trophoblast giant cells during restricted trophoblast invasion in cows.

The bovine placenta is characterized by a limited invasion of trophoblast giant cells (TGC). In contrast to mononuclear trophoblast cells (MTC), TGC are non-polarized cells, which migrate and fuse with single uterine epithelial cells throughout gestation. Fibroblast growth factors (FGF) were shown to be associated with the migratory activity of cells, cell differentiation and angiogenesis, and due to its localization in trophoblast cells were proposed as important regulating factors in hemochorial placentae of rodents and humans, and the (syn)epitheliochorial placenta of pig and sheep. Since migrating bovine TGC are of epithelial origin, but exhibit similarities to mesenchymal cells we hypothesize that the restricted trophoblast invasion in cattle is characterized by a specific FGF expression pattern. Therefore, the spatiotemporal expression of specific FGF factor:receptor pairs, either acting on cells of mesenchymal origin or on epithelial cells was examined in bovine placental tissues throughout gestation and prepartum by immunohistochemistry, semiquantitative RT-PCR and in situ hybridization. FGF1 protein was found in trophoblast, caruncular epithelium (CE) and stroma (CS), stroma of chorionic villi (SCV), and in fetal and maternal blood vessels. FGF2 signals dominated in maternal vascular endothelia (VE), immature TGC, and MTC, whereas staining in other cell types was clearly weaker. FGF7 protein was detected in fetal and maternal blood vessel as well as in immature TGC and MTC predominantly at the chorionic plate. FGFR immunoreaction was localized in immature TGC, MTC, and to a clearly lesser extent in CS, CE and fetal and maternal blood vessels. Mature TGC stained negatively for all examined factors and FGFR. The corresponding mRNAs specific for FGF1, -2, -7, total FGFR, and FGFR2 isoforms IIIb and IIIc were colocalized in immature TGC, whereas hybridization was substantially lower in CE and absent in CS, SCV and mature TGC throughout gestation, but switched to CS and VE immediately prepartum. Semiquantitative RT-PCR revealed higher mRNA levels for FGF1, FGFR, and FGFR2IIIc in cotyledons compared to caruncles (p<0.05), whereas it was the opposite with FGF2 (p<0.001). FGF7 and FGFR2IIIb mRNA levels did not differ between caruncles and cotyledons. Significant changes (p<0.05) of mRNA levels related to gestational age were found for FGF1 and FGFR2IIIc, but not for FGF2, -7, total FGFR, and FGFR2IIIb. The specific localization of all examined FGF family members in TGC suggests that TGC, apart from their classical function as producers of hormonal products, play other important roles in the regulation of bovine placentomal growth, differentiation and angiogenesis.

Animals↗

Activity and expression of 15-hydroxyprostaglandin dehydrogenase in cultured chorionic trophoblast and villous trophoblast cells and in chorionic explants at term with and without spontaneous labor.

OBJECTIVE: The aim of this study was to investigate whether any changes occurred at term before and with labor in the 15-hydroxyprostaglandin dehydrogenase messenger ribonucleic acid level and in the 15-hydroxyprostaglandin dehydrogenase activity in cultured chorionic and villous trophoblast cells and in chorionic explants. STUDY DESIGN: Twelve placentas (labor group [vaginal delivery], n = 6; nonlabor group [elective cesarean delivery], n = 6) were collected. Chorionic trophoblast and villous trophoblast cells and chorionic disks were obtained, cultured, and incubated with 282-nmol/L prostaglandin F(2)(alpha). Medium was collected to measure the 13,14-dihydro-15-keto metabolite of prostaglandin F(2)(alpha), and the cells and disks were snap-frozen to quantify 15-hydroxyprostaglandin dehydrogenase messenger ribonucleic acid expression by Northern blot analysis. RESULTS: The formation of the 13,14-dihydro-15-keto metabolite of prostaglandin F(2)(alpha) was significantly lower in the labor group than in the nonlabor group for both sets of cultured cells and for chorionic explants. 15-Hydroxyprostaglandin dehydrogenase messenger ribonucleic acid expression was lower in the chorionic trophoblast cells and chorionic disks of the labor group than those of the nonlabor group. However, the 15-hydroxyprostaglandin dehydrogenase messenger ribonucleic acid level in the villous trophoblast cells did not differ between the labor and nonlabor groups. CONCLUSION: Prostaglandin metabolic activity in the chorion is reduced significantly at the time of labor.

Blotting, Northern↗

Intermediate trophoblast: a distinctive form of trophoblast with specific morphological, biochemical and functional features.

Morphological and immunohistochemical analysis of placental tissue from 12 days to term using antibodies directed against the unique carboxyl terminal peptide of human chorionic gonadotrophin beta subunit, human placental lactogen (hPL) and pregnancy-specific beta I-glycoprotein reveals that an intermediate form of trophoblast with distinctive features exists. This cell has a diverse morphological expression and is located overlying chorionic villi, in the trophoblastic columns, basal plate and the trophoblastic shell. Although all three placental proteins are localized in this cell the predominant hormone is hPL, which can serve as an immunocytochemical marker. One of the primary functions of this cell is in implantation and in the establishment of the uteroplacental circulation since it extensively invades the spiral arteries at the placental site. It is proposed that this distinctive form of trophoblast be termed 'intermediate trophoblast'.

Chorionic Gonadotropin↗

Immunizing with mouse trophoblast to obtain mouse-human cross-reacting antibodies against normal and neoplastic human trophoblast.

Monoclonal antibodies raised against living, early invasive mouse trophoblast cells were screened on paraffin sections from first- and third-trimester placentas and from hydatidiform moles and choriocarcinoma. Several mouse-human cross-reacting antibodies were recognized, which implies that mouse trophoblast cells can be used as immunogen for producing antibodies against human trophoblast. Among the new antibodies obtained, some were selected for further study. That panel includes a trophoblast specific antibody with capacity to differ between invasive and noninvasive molar tissues, and two antibodies, which detect antigen epitopes in the normal, but not in the neoplastic trophoblast.

Animals↗

Reactivity of two monoclonal antibodies (Troma 1 and CAM 5.2) on human tissue sections: analysis of their usefulness as a histological trophoblast marker in normal pregnancy and trophoblastic disease.

In normal and molar pregnancy, a morphological discrimination between nonvillous trophoblasts which lie scattered in the placental bed and surrounding maternal cells is considered to be difficult. We examined the reactivity of two monoclonal antibodies (Troma 1 and CAM 5.2) against cytokeratin by an immunoperoxidase technique and analyzed their usefulness as a histological trophoblast marker. Materials were taken from 42 uteri with normal pregnancy, 7 uteri with hydatidiform mole, 2 uteri with gestational choriocarcinoma, 1 fallopian tube with nongestational choriocarcinoma, 5 delivered term placentae of normal pregnancy, and 5 nongestational uteri. The reactivities of Troma 1 on frozen sections and those of CAM 5.2 on paraffin sections were identical. They reacted with surface epithelium and gland epithelium in the nongestational uterine corpus. In the implantation site of normal and molar pregnancy, they reacted with villous and nonvillous trophoblasts as well as endometrial gland epithelium. In gestational and nongestational choriocarcinoma, they reacted with carcinoma cells specifically. Since the histological detection of gland epithelium may not be difficult, it was concluded that the two antibodies were very beneficial as a histological marker for trophoblasts in normal pregnancy and trophoblastic disease.

Antibodies, Monoclonal↗

Co-expression of cytokeratins and vimentin by highly invasive trophoblast in the white-winged vampire bat, Diaemus youngi, and the black mastiff bat, Molossus ater, with observations on intermediate filament proteins in the decidua and intraplacental trophoblast.

Histological and immunocytochemical studies of gravid reproductive tracts obtained from the white-winged vampire bat (Diaemus youngi) and the black mastiff bat (Molossus ater) have established that both species develop unusually invasive trophoblast. This is released by the developing discoidal haemochorial placenta, expresses both cytokeratins and vimentin, and invades the myometrium and adjacent tissues (including the ovaries) via interstitial migration within the walls of maternal blood vessels. Hence, this trophoblast is noteworthy for the extent to which it undergoes an epithelial-mesenchymal transformation. In Molossus, it originates from the cytotrophoblastic shell running along the base of the placenta, is mononuclear, and preferentially invades maternal arterial vessels serving the discoidal placenta. This trophoblast may have a role in dilatation of these vessels when the discoidal placenta becomes functional. In Diaemus, the highly invasive trophoblast appears to originate instead from a layer of syncytiotrophoblast on the periphery of the placenta is multinucleated, and vigorously invades both arterial and venous vessels. During late pregnancy, it becomes extensively branched and sends attenuated processes around many of the myometrial smooth muscle fibres. In view of its distribution, this trophoblast could have important influences upon myometrial contractility and the function of blood vessels serving the gravid tract. Other aspects of intermediate filament expression in the uteri and placentae of these bats are also noteworthy. Many of the decidual giant cells in Molossus co-express cytokeratins and vimentin, while the syncytiotrophoblast lining the placental labyrinth in Diaemus late in pregnancy expresses little cytokeratin.

Animals↗

Human chorionic gonadotropin (hCG) beta-core fragment is produced by degradation of hCG or free hCG beta in gestational trophoblastic tumors: a possible marker for early detection of persistent postmolar gestational trophoblastic disease.

The present study was undertaken to investigate whether human chorionic gonadotropin (hCG) beta-core fragment (hCG beta cf) was directly produced by gestational trophoblastic tumors. Immunoreactivity of hCG beta cf was demonstrated in the extracts as well as in the culture media of hydatidiform mole tissues. It was also present in the extracts of choriocarcinoma tissues, and its molar concentration exceeded that of intact hCG. The presence of hCG beta cf was then confirmed by gel chromatography and Western blot analysis. Immunohistochemistry showed localization of hCG beta cf immunoreactivity to the syncytiotrophoblasts and scattered cells in the stroma of mole tissue, and to syncytiotrophoblastic cells in choriocarcinoma. Immunoreactivity of hCG beta cf was also detected in the sera of the patients with gestational trophoblastic disease, although the hCG beta cf/hCG ratio was less than one hundredth of that in the tissue extracts. Serial measurement of serum hCG beta cf levels after mole evacuation showed that they declined much more rapidly than those of hCG and became undetectable in the patients with subsequent spontaneous resolution, while hCG beta cf remained or became detectable before the rise of hCG was observed in the patients with subsequent persistent trophoblastic disease. Taken together, these results suggest that hCG beta cf is directly produced by gestational trophoblastic tumors, and monitoring of hCG beta cf in the serum after mole evacuation may be useful for early prediction of subsequent development of postmolar persistent trophoblastic disease.

Animals↗

Epithelioid trophoblastic tumor: review of a rare neoplasm of the chorionic-type intermediate trophoblast.

We present a brief review of epithelioid trophoblastic tumor, a rare trophoblastic neoplasm derived from chorionic-type intermediate trophoblastic cells that typically presents in reproductive-age women between 1 and 18 years following a previous gestation. Histologic features include a nodular growth pattern of monomorphic, epithelioid cells within a hyaline matrix. Areas of necrosis and mitotic activity (0-9 mitoses per 10 high-power fields) are additional features of this neoplasm. Positive immunostaining for p63 and cytokeratin, frequent location in the lower uterine segment and endocervix, as well as the epithelioid appearance can lead to confusion with squamous cell carcinoma. Inhibin-alpha is typically expressed, as well as focal, more variable expression of other trophoblastic markers including beta-human chorionic gonadotropin, human placental lactogen, placental alkaline phosphate, and Mel-CAM (CD148). The clinical behavior of this rare form of gestational trophoblastic disease is difficult to predict. Although most cases follow a benign course following resection, there is a potential for metastatic disease.

Adult↗

[Diagnostic value of determining chorionic gonadotropin and trophoblastic beta 1-glycoprotein in trophoblastic disease].

The diagnostic value of determinations of the levels of chorionic gonadotropin (HCG) and trophoblastic beta 1-glycoprotein (TBG) was studied in 160 cases of trophoblastic disease. Trophoblastic disease was diagnosed in 86% of cases, when HCG level was determined immunologically and in 100 % -- by radioimmunological means and in 86 and 33% when TBG level was established by immunoradioautographical and immunodiffusion methods, respectively. The results of HCG and TBG assays by immunological and immunoradioautographical methods matched in 96% of cases. The said methods are highly specific and may find a wide application in diagnosing trophoblastic disease. The radioimmunological method of HCG assay is the most sensitive. However, in view of possible HCG synthesis in cases of other tumor, its application should be preferred in assessing the efficacy of therapy rather than for primary diagnosis of trophoblastic disease.

Choriocarcinoma↗

Trophoblastic cells expressing human chorionic gonadotropin genes in peripheral blood of patients with trophoblastic disease.

We attempted to identify the cells expressing alpha and beta subunits of human chorionic gonadotropin (hCG) in the peripheral blood of patients with trophoblastic disease and normal pregnant women by using reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot. By this method, the mRNAs of hCG alpha and hCG beta were detected in the peripheral blood mononulear cells (PBMNC) from 3 of 7 hydatidiform mole (mole) and 1 of 4 choriocarcinoma patients as well as from normal pregnant women during the first trimester. None of the mRNAs of hCG subunits was detected in the PBMNC from healthy male and nonpregnant healthy women examined. The expression of hCG alpha and hCG beta in patients with trophoblastic disease and normal pregnant women almost correlated with their plasma levels of intact hCG. The present study indicates that the cells expressing hCG alpha and hCG beta, which virtually represent trophoblasts, are circulating in the peripheral blood of patients with trophoblastic disease as well as of normal pregnant women.

Blotting, Southern↗