RESUMO
La enfermedad trofoblástica gestacional (ETG) es un trastorno proliferativo del trofoblasto. Incluye la mola hidatidiforme, el coriocarcinoma, la mola invasiva, el tumor trofoblástico del lecho placentario y el tumor trofoblástico epitelioide. Las últimas cuatro hacen parte de la neoplasia trofoblástica gestacional, que agrupa menos del 1% de todos los tumores ginecológicos. La incidencia de la ETG puede variar, siendo aproximadamente de 1 a 3 de cada 1.000 embarazos en América del Norte y Europa. El coriocarcinoma es la forma más agresiva por su rápida invasión vascular y compromiso metastásico. Sin embargo, es un tumor muy quimiosensible con una alta tasa de respuestas y posibilidad de curación superior al 90%. Se presenta el caso de una paciente de 40 años quien ingresó al servicio de urgencias por disnea súbita secundaria a tromboembolia pulmonar y posteriormente tras el inicio de anticoagulación presentó hemoperitoneo debido a lesiones hepáticas metastásicas de un coriocarcinoma, además de compromiso metastásico pulmonar. Se presenta este caso por ser una patología poco frecuente, agresiva y con presentaciones inusuales, con el fin de mostrar la importancia de un diagnóstico y tratamiento oportuno.
Gestational trophoblastic disease (GTD) is a condition in which the trophoblast, a layer of cells surrounding the embryo, develops abnormally. GTD includes both pre-malignant and malignant pathologies, such as hydatidiform mole, choriocarcinoma, invasive mole, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. Although GTD is rare, it affects about 1 to 3 out of every 1,000 pregnancies in North America and Europe. Choriocarcinoma is the most aggressive form of GTD, as it can quickly invade blood vessels and metastasize to other parts of the body. However, it is highly responsive to chemotherapy, with a cure rate of over 90%. In this case, a 40-year-old patient presented to the emergency department with sudden dyspnea due to pulmonary embolism. After starting anticoagulation therapy, she developed hemoperitoneum due to the spread of choriocarcinoma to her liver, as well as pulmonary metastases. This case is noteworthy because of its unusual presentation and aggressive nature, underscoring the importance of early diagnosis and treatment.
Assuntos
Humanos , Feminino , Gravidez , Adulto , Coriocarcinoma/diagnóstico por imagem , Tumor Trofoblástico de Localização Placentária/diagnóstico por imagem , Doença Trofoblástica Gestacional/tratamento farmacológico , Coriocarcinoma/cirurgia , Coriocarcinoma/complicações , Tumor Trofoblástico de Localização Placentária/patologia , Doença Trofoblástica Gestacional/metabolismoRESUMO
Gestational trophoblastic diseases are a group of pregnancy-related disorders, originated from trophoblast cells. They include benign and aggressive tumors, such as the invasive mole, the choriocarcinoma, the placental site trophoblastic tumor (PSTT), and the epithelioid trophoblastic tumor (ETT). These malignancies are characterized as gestational trophoblastic neoplasm (GTN), rarer, although more dangerous. The diagnosis of GTN is made in most cases by monitoring serum chorionic gonadotropin (hCG) with histological confirmation. The use of specific tissue biomarkers has been increasingly employed as a differential diagnosis, leading to more accurate results and different therapy protocols and prognosis for each GTN. The treatment is based on the International Federation of Gynecology and Obstetrics anatomical staging system and the World Health Organization prognostic score system. If an accurate diagnosis is made and the guidelines followed, the cure for choriocarcinoma and invasive mole cases can reach 98%, whereas PSTT and ETT still present mild success rates. The improved knowledge about GTN and its peculiarities allows physicians to efficiently achieve the differential diagnosis and choose the best available therapy protocol, thus increasing the overall survival of affected women. Nevertheless, obtaining epidemiological data and improving knowledge through basic and translational research are essential to answer open questions on GTN physiopathology, their causes, and cellular behavior.
Assuntos
Doença Trofoblástica Gestacional/diagnóstico , Placenta/patologia , Tumor Trofoblástico de Localização Placentária/diagnóstico , Trofoblastos/patologia , Neoplasias Uterinas/diagnóstico , Biomarcadores Tumorais , Diagnóstico Diferencial , Feminino , Doença Trofoblástica Gestacional/metabolismo , Doença Trofoblástica Gestacional/patologia , Humanos , Placenta/metabolismo , Gravidez , Prognóstico , Tumor Trofoblástico de Localização Placentária/metabolismo , Tumor Trofoblástico de Localização Placentária/patologia , Trofoblastos/metabolismo , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologiaRESUMO
Versican is a proteoglycan known to interact with cells to influence their ability to proliferate, differentiate, migrate, invade and assemble extracellular matrix, with all of these cell functions present during placentation. In the placenta, cytotrophoblast cells have the ability to differentiate into the syncytiotrophoblast, a mechanism that is greatly increased in gestational trophoblastic diseases (GTD). Nevertheless, the molecular signaling underlying the increased syncytiotrophoblast differentiation are still being unveiled and may result in novel therapeutic targets for GTD. Versican expression was investigated to establish its differential expression among GTD (partial moles, complete moles, invasive moles and choriocarcinoma) and the possible functional outcomes from versican gene silencing. Tissue samples had their versican expression evaluated using immunohistochemistry and RT-PCR. BeWo cells were employed for versican silencing with siRNA and the efficiency was confirmed by RT-PCR, immunofluorescence and flow cytometry. Cell death and forskolin-induced syncytialization were analyzed by a morphological analysis and human chorionic gonadotropin (hCG) production using immunofluorescence. Versican V0 and V1 isoforms were mainly expressed in the syncytiotrophoblast and they were the most expressed in benign rather than in malignant tumors. BeWo cells also expressed V0 and V1 isoforms, but only in cells undergoing syncytial fusion. After versican silencing, cell death was greatly increased, whereas spontaneous and forskolin-induced syncytialization decreased as well as hCG production. Versican is differentially expressed in GTD and is important for hydatidiform moles pathophysiology, protecting trophoblast cells from death and playing a role in their differentiation and functionality.
Assuntos
Inativação Gênica , Doença Trofoblástica Gestacional/genética , Versicanas/genética , Diferenciação Celular , Feminino , Doença Trofoblástica Gestacional/metabolismo , Doença Trofoblástica Gestacional/patologia , Humanos , Gravidez , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Trofoblastos/metabolismo , Trofoblastos/patologia , Células Tumorais Cultivadas , Versicanas/metabolismoRESUMO
We report the cDNA cloning and characterization of GTT1/StarD7, a novel gestational trophoblastic tumour gene, initially identified by its up-regulated expression in the choriocarcinoma JEG-3 cell line with respect to their nonmalignant counterpart, complete hydatidiform mole and normal trophoblastic tissue. Using the differential display fragment as a probe we screened placenta and HeLa cDNA libraries and isolated a clone carrying a 3315 bp insert (accession number AF270647). This cDNA encodes a protein of 295 amino acid residues with a molecular weight of approximately 34.7 kDa and a pI of 5.79. Computer-mediated homology search revealed that the deduced amino acid sequence had similarity to phosphatidylcholine transfer protein (PCTP) with a conserved StAR-related lipid transfer (START) domain extending between the amino acids 66 to 250. The GTT1 gene contains at least 9 exons spread nearly 30 kb on chromosome 2p12-2p11.2. Northern blot assays of total RNA derived from normal early placenta (NEP), complete hydatidiform mole (CHM) and JEG-3 cell line revealed a 3.5 kb mRNA expressed exclusively in the JEG-3 cell line. However, semiquantitative RT-PCR analysis performed with the same RNA samples demonstrated GTT1 expression throughout all of them with the highest level in JEG-3 cell line. Examination of GTT1 mRNA expression by semiquantitative RT-PCR assays in a series of tumour cell lines indicated wide-spread GTT1 expression with predominance in both choriocarcinoma JEG-3 and JAR cells, colorectal adenocarcinoma HT29 and hepatocellular carcinoma HepG2 cells. In conclusion, the highly GTT1 expression profile in JEG-3 and JAR cell lines and its lipid binding domain suggest that GTT1 may play an important role in the phospholipid-mediated signalling of trophoblastic tumour cellular events.