RESUMEN
CASE PRESENTATION: A 47-year-old woman was admitted to the hospital for an episode of hemoptysis. She coughed out small amount of clotted blood the morning of admission. She had no other symptoms on further review. Her medical history was unremarkable with the exception of an upper respiratory tract infection 9 months previously. She did not have any significant medical history or recent sick contacts. She was a lifelong nonsmoker and the mother of three teenaged children. She had irregular menses for the past 2 years, and her last menstrual period was 3 months ago. She reliably reported not engaging in any sexual contact for the past 2 years.
Asunto(s)
Neoplasias Pulmonares/diagnóstico , Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Quistes/etiología , Femenino , Hemoptisis/etiología , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/metabolismo , Persona de Mediana EdadRESUMEN
Choriocarcinoma can be difficult to differentiate from other subtypes of testicular germ cell tumor and can occur unexpectedly in a distant, late metastasis. The aim of this investigation was to identify a marker superior to ß-human chorionic gonadotropin (ß-hCG) for choriocarcinoma. Sixty-two primary and metastatic testicular germ cell tumors (27 choriocarcinomas, 19 yolk sac tumors, 29 embryonal carcinomas, 28 seminomas, 22 teratomas, 3 epithelioid trophoblastic tumors [ETTs]) were analyzed for immunohistochemical expression of cytokeratin 7 (CK7), inhibin, p63, and ß-hCG. All choriocarcinomas and ETTs were strongly positive for CK7, whereas seminomas were negative and 52% of embryonal carcinomas had weak reactivity. Eighty-four percent of yolk sac tumors and 59% of teratomas were CK7 positive. Eighty-nine percent of choriocarcinomas and 100% of ETTs were positive for inhibin, with reactivity highlighting syncytiotrophoblasts, whereas seminomas, embryonal carcinomas, yolk sac tumors, and teratomas were negative. Eighty-five percent of choriocarcinomas expressed p63, with staining mostly in mononucleated trophoblasts, whereas seminomas, embryonal carcinomas, and yolk sac tumors were negative. Teratomas expressed p63 in 32% of cases. ß-hCG was reactive in 96% of choriocarcinomas, 33% of ETTs, 46% of seminomas, 54% of embryonal carcinomas, 47% of yolk sac tumors, and 32% of teratomas. ß-hCG staining within other subtypes was more likely if choriocarcinoma was present elsewhere in the tumor (Pâ¯=â¯.0002). CK7 is a highly sensitive marker for choriocarcinoma and differentiates choriocarcinoma from seminoma and embryonal carcinoma. Inhibin and p63 are sensitive and specific for choriocarcinoma versus seminoma, embryonal carcinoma, and yolk sac tumor. To identify choriocarcinoma, CK7, inhibin, and p63 are superior to ß-hCG.
Asunto(s)
Biomarcadores de Tumor/análisis , Coriocarcinoma/diagnóstico , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias Testiculares/diagnóstico , Adulto , Gonadotropina Coriónica Humana de Subunidad beta/análisis , Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Humanos , Inhibinas/análisis , Inhibinas/biosíntesis , Queratina-7/análisis , Queratina-7/biosíntesis , Masculino , Proteínas de la Membrana/análisis , Proteínas de la Membrana/biosíntesis , Persona de Mediana EdadRESUMEN
Columnar cell variant of papillary thyroid carcinoma (CCV-PTC) is an unusual neoplasm, the clinical behavior of which mainly depends on the encapsulation or infiltration. Patients with extensive extrathyroidal extension usually have an aggressive biological behavior. This study confirmed that beta-human chorionic gonadotropin (ß-hCG) secreting invasive CCV-PTC has good prognosis comparing with a cohort of follicular cell differentiated thyroid carcinoma. On the contrary, positive immunoreaction with ß-hCG was proved in three anaplastic thyroid carcinoma patients showing aggressive clinical courses. The clinicopathologic characteristics of CCV-PTC and the paraneoplastic syndromes in follicular cell differentiated thyroid carcinoma were further summarized using literature review.
Asunto(s)
Adenocarcinoma Folicular/patología , Carcinoma Papilar/patología , Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Neoplasias de la Tiroides/patología , Adenocarcinoma Folicular/metabolismo , Adenocarcinoma Folicular/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Carcinoma Papilar/metabolismo , Carcinoma Papilar/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/mortalidad , Adulto JovenRESUMEN
BACKGROUND: Ectopic secretion of human chorionic gonadotrophin free beta (hCGß) by epithelial cancer is associated with aggressive tumors which more readily metastasize, possibly by acting as an autocrine anti-apoptotic agent. hCGß is encoded by six homologous CGB genes, with poorly-understood variable transcriptionally active expression profiles; CGB1 and CGB2 have always been considered pseudogenes. However, transcripts from CGB1 and -2 can be detected in placental, testicular and pituitary tissues. The expression and function of these genes in cancer is less well-known. MATERIALS AND METHODS: Expression profiles of CGB genes in epithelial cancer cells by quantitative polymerase chain reaction (qPCR) were explored, along with the consequence of specific siRNA silencing of CGB1 and 2. Immunohistochemical and immunoassay techniques were used to detect the translation and secretion of hCGß in these cells. RESULTS: CGB1 and -2 gene transcripts were only detected in cells which secreted hCGß. siRNA-mediated silencing of CGB1 and -2 transcripts significantly reduced secreted protein in concordance with a reduction in cell survival to a greater degree than that of other CGB genes. CONCLUSION: CGB genes 1 and 2, previously considered as pseudogenes, are notably expressed by epithelial cancer cell lines. The transcription of these genes, but not other CGB genes, correlates with a functionally expressed protein and propensity for cancer growth.
Asunto(s)
Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Gonadotropina Coriónica Humana de Subunidad beta/genética , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Glandulares y Epiteliales/metabolismo , Línea Celular Tumoral , Gonadotropina Coriónica Humana de Subunidad beta/metabolismo , Humanos , Inmunohistoquímica , Isoformas de Proteínas/genética , ARN Interferente Pequeño , Reacción en Cadena en Tiempo Real de la Polimerasa , TranscriptomaRESUMEN
BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a rare, aggressive malignancy with a median survival of five months. Multimodality treatment is associated with some improvement in survival, but patients are only infrequently curable. Although ß-hCG secretion has been reported in many neoplasms, it has never been described in ATC. The objectives of this study were to report a case of ß-hCG-secreting ATC and to study the expression and significance of ß-hCG and PAX8 in an institutional cohort of ATC. METHODS: The sentinel case was characterized and then immunohistochemistry was performed for ß-hCG and PAX8 on 30 ATC patients. Clinical follow-up was obtained by chart review. RESULTS: The sentinel patient with ß-hCG-secreting ATC had a dramatic response to chemotherapy and radiation. After surgical excision of residual disease, the patient developed a regional recurrence of differentiated thyroid carcinoma at 18 months. However, she is now, 30 months after initial therapy, with no evidence of disease and no detectable serum ß-hCG or thyroglobulin. Five of the 30 (17%) total ATCs were positive for ß-hCG and 18 (60%) for PAX8. Outcomes for the ß-hCG-positive cases were not significantly different from those for negative ones. However, none of the other four ß-hCG-positive ATC patients received treatment with either chemotherapy or radiation. Interestingly, PAX8 positivity correlated with statistically significantly better overall survival (p=0.019). CONCLUSIONS: ß-hCG is expressed in a minority of ATCs. Although only a single case in the study had diffuse immunohistochemical expression, the response it showed to aggressive multimodality therapy and the resulting favorable outcome suggest that ß-hCG-positive ATC may be a unique tumor subtype, or possibly even a unique entity. PAX8 is a useful marker of ATC and may be helpful in the differential diagnosis with other malignant neoplasms.
Asunto(s)
Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Factores de Transcripción Paired Box/biosíntesis , Neoplasias de la Tiroides/diagnóstico , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Factor de Transcripción PAX8 , Pronóstico , Tiroglobulina/metabolismo , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugíaRESUMEN
OBJECTIVE: To investigate morphologic differences of the placenta in pregnancies complicated by gestational diabetes compared to nondiabetic pregnancies. STUDY DESIGN: This was a comparative morphological study of the placentas from 20 women with gestational diabetes and 20 healthy pregnancies at 28-35 weeks of gestation. RESULTS: The presence of lesions such as fibrinoid necrosis, villous edema, syncytial knot and vascular lesions like chorangiosis was apparent, mainly in the diabetes group. There was an apparent decrease in the intensity of the human chorionic gonadotropin (hCG) immunostaining in the syncytiotrophoblast from the 28th to 35th weeks of gestation in the placentas of the healthy control group. No hCG immunostaining was observed in the villous or intervillous areas of any of the placentas. In diabetic placentas the expression of hCG was homogeneous with a moderate to intense immunoreactivity in the syncytiotrophoblast. Several syncytiotrophoblast cells showed dilations of both rough and smooth endoplasmic reticulum and loss and alteration of microvilli, and large vacuoles were observed just below the plasma membrane, as well as irregularities in the mitochondria. CONCLUSION: Syncytial cells play an important role in the placental transition. Increased expression of beta-hCG, deterioration, degeneration of organelles and cell structure and the basal membrane disorder in chorionic vessels were seen in placentas with gestational diabetes. These changes can affect placental transfer. However, further studies are needed to clarify this issue.
Asunto(s)
Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Diabetes Gestacional/metabolismo , Diabetes Gestacional/patología , Fragmentos de Péptidos/biosíntesis , Placenta/metabolismo , Placenta/ultraestructura , Adulto , Femenino , Humanos , Inmunohistoquímica , Microscopía Electrónica de Transmisión , Madres , Embarazo , Trofoblastos/metabolismo , Trofoblastos/ultraestructuraRESUMEN
Human chorionic gonadotropin (hCG) displays a major role in pregnancy initiation and progression and is involved in trophoblast differentiation and fusion. However, the site and the type of dimeric hCG production during the first trimester of pregnancy is poorly known. At that time, trophoblastic plugs present in the uterine arteries disappear, allowing unrestricted flow of maternal blood to the intervillous space. The consequence is an important modification of the trophoblast environment, including a rise of oxygen levels from about 2.5% before 10 wk of amenorrhea (WA) to â¼8% after 12 WA. Two specific ß-hCG proteins that differ from three amino acids have been described: type 1 (CGB7) and type 2 (CGB3, -5, and -8). Here, we demonstrated in situ and ex vivo on placental villi and in vitro in primary cultures of human cytotrophoblasts that type 1 and 2 ß-hCG RNAs and proteins were expressed by trophoblasts and that these expressions were higher before blood enters in the intervillous space (8-9 vs. 12-14 WA). hCG was immunodetected in villous mononucleated cytotrophoblasts (VCT) and syncytiotrophoblast (ST) at 8-9 WA but only in ST at 12-14 WA. Furthermore, hCG secretion was fourfold higher in VCT cultures from 8-9 WA compared with 12-14 WA. Interestingly, VCT from 8-9 WA placentas were found to exhibit more fusion features. Taken together, we showed that type 1 and type 2 ß-hCG are highly expressed by VCT in the early first trimester, contributing to the high levels of hCG found in maternal serum at this term.
Asunto(s)
Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Placenta/metabolismo , Primer Trimestre del Embarazo/genética , Primer Trimestre del Embarazo/metabolismo , Trofoblastos/metabolismo , Animales , Western Blotting , Fusión Celular , Separación Celular , Células Cultivadas , Gonadotropina Coriónica Humana de Subunidad beta/genética , Vellosidades Coriónicas/metabolismo , Femenino , Expresión Génica/fisiología , Humanos , Inmunohistoquímica , Consumo de Oxígeno/fisiología , Embarazo , ARN/biosíntesis , ARN/genética , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
The authors present a rare case of primary intracranial leiomyosarcoma (LMS) in a young, immunocompetent boy. The patient presented with an expanding right forehead mass. Diagnostic workup revealed multiple large intracranial tumors. The largest mass was resected, and pathological analysis revealed LMS. Given the poor prognosis of this tumor, the family declined further care, and the child died 3 months later. Primary LMSs are extremely rare tumors in the pediatric population, especially in patients who are not immunocompromised.
Asunto(s)
Neoplasias Encefálicas/metabolismo , Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Leiomiosarcoma/metabolismo , Preescolar , Humanos , Inmunocompetencia , MasculinoRESUMEN
CONTEXT: Vitamin C [ascorbic acid (AA)] is transported by sodium-dependent vitamin C transporters (SVCT) 1 and 2, and our previous studies show AA induces a dramatic production of steroid hormones in human choriocarcinoma cells. However, whether AA induces the production of placental polypeptide hormones remains unknown. Here we investigated the mechanisms governing AA-induced ß-human chorionic gonadotropin (hCG) expression. METHODS: Frozen sections from human term placentas were used for immunostaining of SVCT, and ßhCG mRNA expression and its production in primary human placental cytotrophoblasts and JEG-3 cells were examined by quantitative RT-PCR and ELISA, respectively. Knockdown of SVCT2, transcription factor activating enhancer-binding protein 2α (TFAP2A), or specificity protein-1 (Sp1) expression was achieved by retrovirus-mediated short hairpin RNA, and the transcriptional factors responsible for AA-induced ßhCG expression was identified by reporter constructs. RESULTS: Both SVCT1 and SVCT2 are expressed in human term placentas. SVCT2 is predominantly localized in the syncytial layer, whereas SVCT1 is predominantly distributed in the villous core. AA dramatically induces ßhCG mRNA expression and its production in JEG-3 cells and primary human cytotrophoblasts, and knockdown of SVCT2 expression in JEG-3 cells significantly decreases AA-induced ßhCG expression. Data from ßhCG5 construct and its deletion mutants further indicate that AA induces ßhCG5 transactivation through Sp1 and TFAP2A transcriptional factors, and silence of Sp1 and/or TFAP2A expression significantly decreased AA-induced ßhCG5 reporter activity and ßhCG expression as well. CONCLUSIONS: The present study revealed the novel effects of AA on polypeptide hormone, ßhCG, production and the potential mechanisms governing AA-induced ßhCG expression, suggesting the potentially indispensable roles of AA in placental endocrine and pregnant maintenance.
Asunto(s)
Ácido Ascórbico/metabolismo , Ácido Ascórbico/farmacología , Coriocarcinoma/metabolismo , Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Transportadores de Sodio Acoplados a la Vitamina C/metabolismo , Factor de Transcripción Sp1/genética , Factor de Transcripción AP-2/genética , Adulto , Western Blotting , Línea Celular Tumoral , AMP Cíclico/análisis , AMP Cíclico/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica del Anticuerpo Fluorescente , Vectores Genéticos , Humanos , Placenta/metabolismo , Plásmidos/genética , Embarazo , ARN Mensajero/biosíntesis , ARN Interferente Pequeño/biosíntesis , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Retroviridae/genéticaRESUMEN
BACKGROUND: Research on antimicrobial cationic peptides (AMPs) has gained pace toward using their potential to replace conventional antibiotics. These peptides preferentially interact with negatively charged membrane lipids typically seen in bacteria and thereby lead to membrane perturbations and membrane dysfunction. However, one possible disadvantage of AMP drugs is their potential for toxicity, especially to those cells which display externalization of negatively charged moieties to the outer leaflet of the plasma membrane during the process of syncytialization. Human placental villous trophoblast is one such cell type. Indeed, intra-vaginal administration of an antimicrobial cationic peptide Ala8,13,18-magainin II amide (AMA) which is a synthetic analogue of magainin 2 derived from Xenopus frog has been observed to result in inhibition of pregnancy establishment in monkeys. However, only little is known about the cellular behavior of early placental cytotrophoblasts (CTB) in the presence of cationic antimicrobial peptides. It is believed that suitable cell culture approaches using AMA as a representative alpha-helical AMP may yield tangible knowledge in this regard. METHODS: Immunocytochemical (ICC) analyses using confocal microscopy (n = 6 for each treatment sub-group) and Western blot (WB) method (n = 5 for each treatment sub-group) of CTB differentiation based on synthesis of beta-hCG and hPL, and apoptosis based on apoptosis-associated cytokeratin 18 neo-epitope (CK18f) were performed for CTB isolated from human first trimester placental villi and grown in serum-free primary culture for 24 h, 48 h and 96 h on rat-tail collagen with and without AMA (1000 ng/ml). Moreover, secretion of beta-hCG and hPL into conditioned media from isolated CTB grown in vitro for 24 h, 48 h and 96 h (n = 6/each sub-group) with and without AMA was examined using enzyme immunoassays. Furthermore, TUNEL assay, and cell viability based on LDH leakage into medium (n = 6/each sub-group) were assessed to examine the phenomenon of cell death with time and administration of AMA. RESULTS: CTB in serum-free primary culture showed increased (P < 0.05) level of synthesis and secretion of beta-hCG and hPL with time, and higher (P < 0.05) level of cellular cytokeratin 18 neo-epitope and number of TUNEL-positive cells, and LDH activity in conditioned medium at 96 h of culture. Exposure of CTB to AMA resulted in lower (P < 0.05) level of synthesis and secretion of beta-hCG and hPL, as well as, an increase (P < 0.05) of cellular cytokeratin 18 neo-epitope and number of TUNEL-positive cells, and LDH activity in conditioned medium at 96 h as compared to the control treatment. CONCLUSIONS: Administration of AMA resulted in attenuation of differentiation, enhancement in apoptosis and loss of viability in early placental villi trophoblast cells in primary culture. Thus, it appears that administration of alpha-helical AMP may adversely affect the process of placentation and pregnancy outcome.
Asunto(s)
Péptidos Catiónicos Antimicrobianos/farmacología , Trofoblastos/efectos de los fármacos , Trofoblastos/metabolismo , Adulto , Apoptosis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Femenino , Humanos , Queratina-18/biosíntesis , L-Lactato Deshidrogenasa/metabolismo , Lactógeno Placentario , Embarazo , Primer Trimestre del EmbarazoRESUMEN
Hyperglycosylated hCG (hCG-H) is a glycoprotein with the same polypeptide structure as hCG, and much larger N- and O-linked oligosaccharides. The oligosaccharides increase the molecular weight of hCG from 36,000 - 37,000 u to 40,000 - 41,000 u, depending on the extent of hyperglycosylation. hCG-H has triantennary N-linked oligosaccharides and double molecular size O-linked oligosaccharides (hexasaccharide compared with predominantly trisaccharide structures). hCG is produced by syncytiotrophoblast cells while hCG-H is made by extravillous cytotrophoblast cells. hCG-H promotes trophoblast invasion during choriocarcinoma, growth of cytotrophoblast cells and placental implantation in pregnancy. hCG-H is an independent molecule to hCG with totally separate biological functions. hCG has numerous functions during pregnancy, it promotes progesterone production, promotes angiogenesis in uterine vasculature, immuno-suppresses the invading placental tissue, promotes the growth of the uterus in line with the growth of the fetus during pregnancy, promotes the differentiation of growing cytotrophoblast cells, promotes the quiescence of contractions in the uterine myometrium during the course of pregnancy, and also has function in growth and development of fetal organs. Monoclonal antibody B152 uniquely binds hCG-H. Using this monoclonal antibody in immunometric assays permits detection of pregnancy. It also permits management of gestational trophoblastic diseases and detection of quiescent gestational trophoblastic disease. This same test can be used to differentiate of aggressive and minimally-aggressive gestational trophoblastic disease, and discrimination of patients that respond to chemotherapy and who are chemorefractory. The hCG-H test can be used to screen for Down syndrome pregnancies and predict patients likely to generate hypertensive disorder in pregnancy. It also can be used to differentiate pregnancies that will miscarry and pregnancies that will go to term.
Asunto(s)
Biomarcadores de Tumor/sangre , Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Gonadotropina Coriónica/biosíntesis , Implantación del Embrión , Glicoproteínas/biosíntesis , Aborto Espontáneo/sangre , Animales , Gonadotropina Coriónica/sangre , Gonadotropina Coriónica/química , Gonadotropina Coriónica Humana de Subunidad beta/sangre , Gonadotropina Coriónica Humana de Subunidad beta/química , Síndrome de Down/sangre , Evolución Molecular , Femenino , Enfermedad Trofoblástica Gestacional/sangre , Glicoproteínas/sangre , Glicoproteínas/química , Humanos , Hipertensión Inducida en el Embarazo/sangre , Embarazo , Pruebas de EmbarazoRESUMEN
The ectopic hormone production by tumor cells that have a light optical structure of typical non-endocrine cancers has long attracted the attention of investigation all over the world. Specifically, this concerns the phenomenon of the ectopic production of the beta-subunit of human chorionic gonadotropin (beta-hCG) by non-germinogenic tumors, which is, according to R.K. Iles's data, encountered in 20-40% of malignant epithelial tumors. Despite the fact that beta-hCG synthesis is traditionally regarded as the prerogative of germinogenic tumors, the world's literature contains strong evidence for latent beta-hCG gene expression and many cases of clinically evident manifestation of the effects of chorionic gonadotropin. The latter fact, if a clinician and a pathologist are unaware of the behavior of a tumor, may give rise to a diagnostic error and incorrect treatment policy.
Asunto(s)
Carcinoma de Células en Anillo de Sello/metabolismo , Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Neoplasias Gástricas/metabolismo , Adulto , Humanos , MasculinoRESUMEN
In spite of the high incidence of transitional cell carcinoma, cutaneous metastases are infrequent, especially when they are the first sign of metastatic spread, with a low survival rate. Thirty five per cent of transitional cell carcinoma of the bladder have ectopic beta- human chorionic gonadotropin (beta-HCG) production. It has been related with high grade tumors, advanced stage, metastatic disease, radioresistent tumors and low survival rate because of its effect as a growth modulator with a probably antagonist action in the apoptotic cascade. We present a thirty six years old woman affected by a transitional cell carcinoma of the bladder producing beta-HCG that showed two cutaneous metastases as first sign of metastatic disease. The exceptional coincidence of these two circumstances announced a very aggressive tumor behaviour and bad prognostic, with a quickly multiple metastatic dissemination including a pericardic metastases.
Asunto(s)
Carcinoma de Células Transicionales/secundario , Neoplasias Cutáneas/secundario , Neoplasias de la Vejiga Urinaria/patología , Adulto , Carcinoma de Células Transicionales/metabolismo , Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Femenino , Humanos , Neoplasias Cutáneas/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
The objective of this study was to determine whether beta human chorionic gonadotropin (hCG) (CGB) subunits and alpha hCG (CGA) subunits are expressed and the hCG dimer is produced in normal human cyclic endometrium. Endometrial specimens were collected for histological dating from women undergoing treatment in our division of human reproduction. RNA from normal secretory endometrium was extracted, and CGB and CGA gene expression was assessed by semiquantitative PCR. Adequate secretory endometrial specimens were homogenized using protease inhibitors. Proteins present in the supernatant were separated electrophoretically, and molecular hCG isoforms were detected by Western blot. The supernatant hCG concentrations were measured by ELISA. We characterized hCG and leukocytes in endometrial specimens by immunohistochemistry. Uterine flushing was performed to confirm endometrial hCG secretion into the uterine fluid. A full-length CGB mRNA encompassing the exon 1 promoter region and the structure exons 2 and 3 (including the C-terminal peptide) was expressed in normal secretory endometrial specimens (similar to CGA) during the early secretory phase of the menstrual cycle, up to an optimum at the midsecretory to late secretory phases. In homogenate supernatants obtained from normal secretory endometrium, hormone concentrations of dimeric hCG were approximately 5 mU per 10 mg of tissue, compared with considerably smaller concentrations of corresponding single free CGB subunit. Single chains of CGB, CGA, and dimeric molecular hCG isoforms were found in endometrial specimens by Western blot. Glandular endometrial hCG production is demonstrated immunohistochemically, with an increase toward the late secretory phase vs. the early secretory phase of the normal secretory menstrual cycle. However, glandular hCG release is diminished or absent in the dyssynchronous or missing endometrial secretory transformation. Endogenous endometrial hCG may be important for implantation and maintenance of pregnancy.
Asunto(s)
Gonadotropina Coriónica/biosíntesis , Gonadotropina Coriónica/genética , Endometrio/metabolismo , Ciclo Menstrual/genética , Ciclo Menstrual/metabolismo , Secuencia de Bases , Western Blotting , Gonadotropina Coriónica/química , Gonadotropina Coriónica/metabolismo , Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Gonadotropina Coriónica Humana de Subunidad beta/química , Gonadotropina Coriónica Humana de Subunidad beta/genética , Cartilla de ADN/genética , Dimerización , Endometrio/anatomía & histología , Epitelio/anatomía & histología , Epitelio/metabolismo , Femenino , Expresión Génica , Hormonas Glicoproteicas de Subunidad alfa/biosíntesis , Hormonas Glicoproteicas de Subunidad alfa/química , Hormonas Glicoproteicas de Subunidad alfa/genética , Humanos , Inmunohistoquímica , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
OBJECTIVE: Beta-human chorionic gonadotropin (HCG) and pregnancy-associated plasma protein (PAPP-A) are placentally produced proteins whose levels are altered in pregnancies with trisomy 21. PLAC4 is located on chromosome 21 and its expression is restricted to the placenta. Here we investigated whether the levels of beta-HCG-, PAPP-A- and PLAC4 mRNA could be able to discriminate pregnancies whose fetus is affected by trisomy 21. METHOD: Hundred and forty-three blood samples from normal pregnancies and eight samples from trisomic pregnancies were collected. Total RNA was extracted from whole maternal blood, reverse-transcribed and the three mRNAs were quantified by real-time quantitative PCR. Hundred and nine controls were also tested for the serum levels of PAPP-A and HCG proteins. RESULTS: Beta-HCG and PLAC4 mRNAs were detected in all samples, in higher amounts than in plasma, whereas the detection rate for PAPP-A mRNA was below 10%. The levels of beta-HCG mRNA significantly correlated with the circulatory concentrations of the HCG protein. However, neither beta-HCG- nor PLAC4 mRNAs show a significant difference between cases and controls. CONCLUSION: Maternal blood levels of beta-HCG-, PLAC4- and PAPP-A mRNAs are not useful markers for the screening of pregnancies with trisomy 21 as their concentrations are either not significantly altered (beta-HCG and PLAC4) or too low to be detected (PAPP-A).
Asunto(s)
Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Síndrome de Down/genética , Proteína Plasmática A Asociada al Embarazo/biosíntesis , Diagnóstico Prenatal/métodos , Estudios de Casos y Controles , Gonadotropina Coriónica Humana de Subunidad beta/sangre , Gonadotropina Coriónica Humana de Subunidad beta/genética , Síndrome de Down/sangre , Femenino , Humanos , Embarazo , Proteína Plasmática A Asociada al Embarazo/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
This report describes the case of 74-year-old man who had a gastric yolk sac tumor complicated with beta human chorionic gonadotropin (beta hCG) producing metastases. He was a heavy drinker. He was admitted to the hospital for abdominal pain and fullness. Based on computed tomography and gastric endoscopy he was diagnosed to have gastric cancer that had metastasized to the liver, lung and lymph nodes. The level of serum alpha fetoprotein (AFP) was high at 523 ng/mL. He died of multiorgan failure six days after admission. The autopsy revealed the stomach tumor to be an AFP-positive yolk sac tumor. Lymph node metastases showed the same characteristics as the stomach tumor. However, the lesions on the liver and lung were negative for AFP and positive for hCG. The yolk sac tumor seemed to have retrodifferentiated to form an hCG-producing tumor in the metastatic lesions. A gastric yolk sac tumor is extremely rare and only eight cases of gastric yolk sac tumors have been previously reported in the literature. To avoid a misdiagnosis, careful attention should be paid to the above-mentioned morphological features and immunohistochemical findings, in addition to the clinical findings.
Asunto(s)
Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Tumor del Seno Endodérmico/diagnóstico , Ganglios Linfáticos/patología , Neoplasias Gástricas/diagnóstico , Anciano , Biomarcadores de Tumor/biosíntesis , Tumor del Seno Endodérmico/metabolismo , Resultado Fatal , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Ganglios Linfáticos/metabolismo , Metástasis Linfática/diagnóstico , Masculino , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/secundario , alfa-Fetoproteínas/biosíntesisRESUMEN
AIMS: To investigate the correlation of beta-subunit of human chorionic gonadotrophin (hCG beta) expression by cervical carcinomas with measures of tumour apoptosis. METHODS AND RESULTS: Eighty-nine cervical carcinoma patients' samples were subject to hCG beta immunohistochemistry and scored with respect to intensity of immunopositivity and percentage of positive cells. Apoptosis was evaluated by three independent parameters: morphological characteristics [haematoxylin and eosin (H&E)], terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL) and poly (ADP-ribose) polymerase (PARP) immunopositivity. Of the 12 adenocarcinomas, only one (8%) was hCG beta+. However, 87% (61/70) of the squamous cell and 100% (7/7) of adenosquamous cell carcinomas were hCG beta+. hCG beta reactivity and intensity was predominantly confined to peripheral tumour cells at the stromal-epithelial interface. Correlation analysis showed that H&E and PARP apoptotic immunopositivity negatively correlated with hCG beta expression (P < 0.001 and P = 0.028 respectively), whereas TUNEL did not (P = 0.12). However, immunopositivity for apoptotic cells by TUNEL was significantly less in tumours where hCG beta expression was greater (scoring >or= 6) and vice versa. hCG beta immunopositivity was also observed in newly formed blood vessels, as well as tumour cells within lymphatic vessels. When tumour vascularization was taken into account, samples with noted vascularization positively correlated with hCG beta scoring. CONCLUSIONS: hCG beta expression correlates with reduced tumour cell apoptosis and may be involved in tumour vascularization and dissemination.
Asunto(s)
Apoptosis/fisiología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Carcinoma Adenoescamoso/irrigación sanguínea , Carcinoma Adenoescamoso/metabolismo , Carcinoma Adenoescamoso/patología , Carcinoma de Células Escamosas/irrigación sanguínea , Femenino , Humanos , Invasividad Neoplásica , Neoplasias del Cuello Uterino/irrigación sanguíneaRESUMEN
A 74-year-old man visited our hospital presenting with pollakisuria. Cystoscopy revealed a bladder cancer with necrotic tissue. The patient was initially treated by transurethral resection of bladder tumor (TUR-Bt). Pathologically, the tumor was shown to be a carcinoma of bladder with human chorionic gonadotropin (hCG) positivity. After TUR-Bt, chemotherapy with M-VAC (methotrexate, vinblastine, adriamycine and cisplatin) was performed. This patient is still alive eight months after resection. To our knowledge, there are 37 cases of beta-hCG-producing urothelial carcinoma of the urinary bladder reported in the Japanese literature.
Asunto(s)
Carcinoma/metabolismo , Gonadotropina Coriónica Humana de Subunidad beta/biosíntesis , Síndromes Paraneoplásicos Endocrinos/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/terapia , Humanos , Masculino , Síndromes Paraneoplásicos Endocrinos/terapia , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
BACKGROUND: Luteinizing hormone (LH) and human chorionic gonadotropin (HCG) target their receptor in gonadal and nongonadal cells to stimulate steroidogenesis and cell growth. The aim of the present study was to investigate the expression of HCG/LH-R in endometriosis to elucidate a possible impact of LH and HCG on this disease. MATERIALS AND METHODS: Analysis of HCG/LH-R protein expression in 23 paired samples of ectopic and eutopic tissue of cycling women with endometriosis and in endometrial samples from 22 healthy controls was conducted via immunofluorescence. HCG and HCG/LH-R gene expression in endometriotic lesions was confirmed by reverse-transcriptase polymerase chain reaction. RESULTS: In endometriotic implants, epithelial HCG/LH-R was found in 12/23 samples. No significant differences in HCG/LH-R levels were observed when compared with glands of uterine endometrium from the same patients or healthy controls. Messenger RNA transcripts for HCG were detected in all 12 samples, whereas HCG/LH-R mRNAs were observed in 10 of the 12 endometriotic lesions investigated. CONCLUSIONS: Although HCG/LH-R was not found to be selectively upregulated in endometriosis, the mere presence of HCG/LH-R in endometriotic tissue may suggest sensitivity of endometriosis to HCG and LH that target HCG/LH-R.