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Uterine tumours resembling ovarian sex cord tumours of the uterine cervix are highly sporadic. Cervical liquid-based cytology revealed two cell patterns: spindle-nucleated cells and polygonal cells.
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Neoplasias do Colo do Útero , Neoplasias Uterinas , Feminino , Humanos , Colo do Útero/patologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Citologia , Citodiagnóstico , Neoplasias Uterinas/patologiaRESUMO
The authors encountered a case of uterine cervical adenosarcoma with sarcomatous overgrowth during pregnancy. Cytological images of atypical stromal cells in sarcoma components were obtained in this case.
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Adenossarcoma , Neoplasias do Colo do Útero , Neoplasias Uterinas , Colo do Útero , Feminino , Humanos , Gravidez , Neoplasias do Colo do Útero/diagnósticoRESUMO
Practices for planned birth among women with low-risk pregnancies vary by birth setting, medical professional, and organizational system. Appropriate monitoring is essential for quality improvement. Although sets of quality indicators have been developed, their applicability has not been tested. To improve the quality of childbirth care for low-risk mothers and infants in Japanese hospitals, we developed 35 quality indicators using existing clinical guidelines and quality indicators. We retrospectively analysed data for 347 women in Japan diagnosed with low-risk pregnancy in the second trimester, admitted between April 2015 and March 2016. We obtained scores for 35 quality indicators and evaluated their applicability, i.e., feasibility, improvement potential, and reliability (intra- and inter-rater reliability: kappa score, positive and negative agreement). The range of adherence to each indicator was 0-95.7%. We identified feasibility concerns for six indicators with over 25% missing data. Two indicators with over 90% adherence showed limited potential for improvement. Three indicators had poor kappa scores for intra-rater reliability, with positive/negative agreement scores 0.94/0.33, 0.33/0.95, and 0.00/0.97, respectively. Two indicators had poor kappa scores for inter-rater reliability, with positive/negative agreement scores 0.25/0.92 and 0.68/0.61, respectively. The findings indicated that these 35 care quality indicators for low-risk pregnant women may be applicable to real-world practice, with some caveats.
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Parto Obstétrico/normas , Hospitais/normas , Prontuários Médicos , Indicadores de Qualidade em Assistência à Saúde , Adulto , Estudos de Viabilidade , Feminino , Humanos , Recém-Nascido , Masculino , Variações Dependentes do Observador , Gravidez , Estudos Retrospectivos , Fatores de RiscoRESUMO
Preeclampsia/hypertensive disorders of pregnancy (PE/HDP) is a serious and potentially life-threatening disease. Recently, PE/HDP has been considered to cause adipose tissue inflammation, but the detailed mechanism remains unknown. We exposed human primary cultured adipocytes with serum from PE/HDP and healthy controls for 24 h, and analyzed mRNA expression of several adipokines, cytokines, and ligands of the receptor for advanced glycation endproducts (RAGE). We found that the mRNA levels of interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), high mobility group box 1 (HMGB1), and RAGE were significantly increased by the addition of PE/HDP serum. Among RAGE ligands, advanced glycation endproducts (AGE) and HMGB1 increased mRNA levels of IL-6 and CCL2 in SW872 human adipocytes and mouse 3T3-L1 cells. The introduction of small interfering RNA for RAGE (siRAGE) into SW872 cells abolished the AGE- and HMGB1-induced up-regulation of IL-6 and CCL2. In addition, lipopolysaccharide (LPS), a ligand of RAGE, increased the expression of IL-6 and CCL2 and siRAGE attenuated the LPS-induced expression of IL-6 and CCL2. These results strongly suggest that the elevated AGE, HMGB1, and LPS in pregnant women up-regulate the expression of IL-6 and CCL2 via the RAGE system, leading to systemic inflammation such as PE/HDP.
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Adipócitos/metabolismo , Hipertensão Induzida pela Gravidez/sangue , Pré-Eclâmpsia/sangue , Receptor para Produtos Finais de Glicação Avançada/genética , Soro/química , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adulto , Animais , Linhagem Celular Tumoral , Células Cultivadas , Quimiocina CCL2/genética , Meios de Cultura/química , Meios de Cultura/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína HMGB1/genética , Humanos , Interleucina-6/genética , Camundongos , Gravidez , Interferência de RNARESUMO
AIMS: In October 2017, the 'Prenatal and Postnatal Health Care Service in Nara (PPHSN)' has piloted the introduction of a new telephone consultation service to support prenatal and postnatal health care and childcare. This study aimed to document the feasibility, acceptability and satisfaction with the service provided by a trained nurse specialist who can access to clinician support when necessary. METHODS: The pilot study was conducted between November 2017 and February 2018. Japanese women who are undergoing a health checkup at the Nara Medical University hospital for delivery and post-partum women who had recently (<1 year) given birth at this hospital (they are raising a child) were invited to participate in the study. They called a free mobile phone number, and spoke to a trained nurse to consult maternal and newborn care practices. The PPHSN project also provided information for supporting raising a child. The postal survey of the PPHSN service was conducted in March 2018. RESULTS: A total of 26 participants were enrolled. The questionnaire was answered by 23 (88.5%) participants, of which over half (52.2-95.7%) of participants declared they were 'strongly agree' plus 'agree' regarding 'patient-centered care', 'communication and information', 'technical quality', 'efficiency', 'access and convenience (feasibility)', and 'willing to use the service again (acceptability)'. The majority (95.7%) of respondents reported being willing to use the service again for a similar health problem. CONCLUSION: This study provided the first evidence of satisfaction with telephone or social networking consultation service by nurse specialists in Japan.
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Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Satisfação do Paciente/estatística & dados numéricos , Cuidado Pós-Natal/psicologia , Cuidado Pré-Natal/psicologia , Telemedicina/métodos , Adulto , Estudos de Viabilidade , Feminino , Humanos , Recém-Nascido , Japão , Projetos Piloto , Cuidado Pós-Natal/métodos , Gravidez , Cuidado Pré-Natal/métodos , Encaminhamento e Consulta , Inquéritos e Questionários , TelefoneRESUMO
OBJECTIVE: Twin pregnancy with complete hydatidiform mole and coexisting fetus (CHMCF) is rare and associated with severe complications during pregnancy and subsequent gestational trophoblastic disease (GTD). We encountered a case of multiple metastatic GTD after a twin pregnancy with CHMCF, following conventional in vitro fertilization (IVF). Only one case of metastatic GTD after CHMCF due to assisted reproductive technology (ART) has been reported. Here, we present the clinical course and reveal the clinical features of CHMCF after ART through a literature review. CASE REPORT: A 42-year-old primigravida woman had an abnormal pregnancy (i.e., CHMCF) by IVF. She had persisting severe vaginal bleeding, which led to termination of her pregnancy at 10 weeks of gestation. Pathohistological examination revealed that this was a case of CHMCF. Five weeks after the termination, the serum ß-human chorionic gonadotropin level was still extremely high, and systemic contrast-enhanced computed tomography revealed a tumor in the uterine corpus and more than 30 lung nodules. After 11 cycles of combination chemotherapy with etoposide, methotrexate, actinomycin-D, cyclophosphamide, and vincristine (EMA/CO) to treat high-risk GTD, hysterectomy was needed as radical therapy. CONCLUSION: Cases of CHMCF following ART may also have higher malignant potential and higher risk of GTD development and become more aggressive biologically. The clinical course of CHMCF after ART seems to be almost the same as that without ART based on the results of literature review.
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Fertilização in vitro/efeitos adversos , Doença Trofoblástica Gestacional/patologia , Mola Hidatiforme/patologia , Complicações Neoplásicas na Gravidez/patologia , Gravidez de Gêmeos , Aborto Induzido , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gonadotropina Coriônica Humana Subunidade beta/sangue , Ciclofosfamida/uso terapêutico , Dactinomicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Idade Gestacional , Doença Trofoblástica Gestacional/tratamento farmacológico , Doença Trofoblástica Gestacional/cirurgia , Humanos , Histerectomia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Metotrexato/uso terapêutico , Gravidez , Tomografia Computadorizada por Raios X/métodos , Hemorragia Uterina , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgia , Vincristina/uso terapêuticoRESUMO
INTRODUCTION: There are several sets of criteria for the diagnosis of Amniotic Fluid Embolism (AFE), but little is known about their degree of agreement. AIM: To evaluate the concordance of the Japan criteria for AFE in comparison with two definitions: the US AFE registration entry criteria (the US criteria) and UK Obstetric Surveillance System criteria for defining cases of amniotic fluid embolism (the UK criteria). MATERIALS AND METHODS: A retrospective observational study was conducted in which the AFE cases registered in the Obstetrical Gynaecological Society of Kinki District in Japan for the period of April 2005 to December 2012 have been analysed by the expert steering obstetric committee, organized by the members of the Obstetric Research group. Cohen's kappa coefficient was used to calculate the agreement among three clinical diagnoses. For inter-group comparison, the Pearson Chi-square test was used (for categorical) and Mann-Whitney test was used (for continuous variables). RESULTS: Among the 26 cases registered for this period, a total of 18 women were selected as having AFE according to the Japan criteria. Five women died (case fatality rate 27.8%). Agreement between the Japan criteria and the US and UK criteria was k = 0.453 and k = 0.538, respectively, reflecting moderate agreement. However, only 38.9% were given a diagnosis of AFE according to all three criteria. The factor that most often caused disagreement in diagnosis between the Japan criteria and the US criteria was "onset within 30 minutes postpartum". The UK criteria excluded "women with postpartum haemorrhage as the first presenting feature in whom there was no evidence of cardiorespiratory compromise". The case fatality rates in US and UK are higher than in Japan (50.0% and 38.5% vs 27.8%), but this did not result in a significant difference (p=0.497). CONCLUSION: The groups of subjects identified as having AFE by the Japan criteria had a medium agreement with the US (k=0.453) or UK criteria (k=0.538). These three definition criteria identified different subgroups of patients. Such disagreement has serious implications for research and treatment.
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OBJECTIVE: Previous studies have reported that concentrations of squamous cell carcinoma (SCC) antigen in amniotic fluid are extremely higher than that in the maternal serum. The aim of this study was to assess the potential clinical utility of vaginal fluid SCC level as a marker for diagnosing premature rupture of membranes (PROM). METHODS: A case-control study was performed using patients admitted to Nara Medical University Hospital, delivery ward, from January 2011 to December 2012. The discriminatory potential of SCC assay was determined using 54 PROM and 108 gestational age-matched control vaginal fluid samples, in a 1:2 ratio. Levels of vaginal fluid SCC in patients with PROM and control pregnant women were quantified by an enzyme-linked immunosorbent assay. RESULTS: The statistical results showed no correlation between gestational age and vaginal fluid SCC levels. There was no significant difference in vaginal fluid SCC levels between patients with PROM and those with control pregnant women (16156.5 ± 10495.8 ng/mL versus 15471.9 ± 11362.2 ng/mL, p = 0.467). CONCLUSION: We conclude that SCC could not be regarded as a potential marker for diagnosis of PROM. SCC may be a physiologic constituent of the vaginal fluid during pregnancy.
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Antígenos de Neoplasias/metabolismo , Ruptura Prematura de Membranas Fetais/diagnóstico , Serpinas/metabolismo , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Ruptura Prematura de Membranas Fetais/metabolismo , Humanos , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Estudos Retrospectivos , Vagina/metabolismoRESUMO
Severely decreased ADAMTS13 unbound to VWF may play a key role in the pathogenesis of HELLP syndrome.A qualitative ADAMTS13 assay may be important for diagnosing HELLP syndrome.
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OBJECTIVE: To determine the relationship between preterm labor and delivery, and the pH and buffer capacity of vaginal secretions. METHODS: Between January 1, 2009 and March 31, 2012, two cohorts of patients at 22-36weeks of pregnancy were enrolled in a prospective cohort study at Nara Medical University Hospital, Japan. Patients experiencing preterm contractions and a control group of patients experiencing normal pregnancies were included. The pH and buffer capacity of vaginal secretions were measured and compared. RESULTS: Of the 237 patients enrolled, 48 (20.3%) were experiencing symptoms of preterm labor and 189 (79.7%) were included in the control group. The pH was higher (P<0.001) and the buffer capacity was lower (P=0.0135) in the vaginal secretions of the patients experiencing preterm contractions compared with the control group. There was no difference in the pH and buffer capacity of the vaginal secretions of symptomatic patients who would experience preterm delivery and those who would not. Receiver operating characteristic curve analyses demonstrated that vaginal-secretion pH and buffer capacity could differentiate between patients experiencing preterm contractions and those not, but could not differentiate between patients who would experience preterm delivery and those who would not. CONCLUSION: Vaginal-secretion pH and buffer capacity could be useful in diagnosing preterm labor; further studies are needed to determine potential practical diagnostic criteria.
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Trabalho de Parto Prematuro/diagnóstico , Vagina/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Concentração de Íons de Hidrogênio , Japão , Valor Preditivo dos Testes , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Curva ROC , Fatores de Risco , Adulto JovemRESUMO
Two histologic types, clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC), are the common histology in ovarian cancer patients who have associated endometriosis. However, both tumor types have distinct clinicopathological characteristics and molecular phenotypes. EAC is predominantly positive for estrogen receptor (ER), but CCC specifically exhibits lower ER expression. This study reviews the current understanding of the role of the ER information in the pathogenesis of CCC, as well as the English language literature for biochemical studies on ER expression and estrogenic action in CCC. The iron-mediated oxidative stress occurs due to repeated hemorrhage in endometriosis, then this compound oxidatively modifies genomic DNA and, subsequently, ER depletion may be observed. There are a number of factors that interfere with ER expression and estrogen activity, which include DNA methylation of the promoter region, histone deacetylation, heme and iron binding, chromatin remodeling and ubiquitin ligase activity. Loss of estrogen function may be a turning point in CCC progression and aggressiveness.
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Inflammation plays a role in the pathogenesis of endometriosis. Endometriosis-associated ovarian carcinogenesis might be promoted through oxidative stress-induced increased genomic instability, aberrant methylation, and aberrant chromatin remodeling, as well as mutations of tumor suppressor genes. Aberrant expression of ARID1A, PIK3CA, and NF-kB genes has been recognized as the major target genes involved in oxidative stress-induced carcinogenesis. HNF-1beta appears to play a key role in anti-oxidative defense mechanisms. We discuss the pathophysiologic roles of oxidative stress as somatic mutations as well as highly specific agents that effectively modulate these targets.
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Endometriose/complicações , Endometriose/metabolismo , Neoplasias Ovarianas/metabolismo , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/metabolismo , Antioxidantes/uso terapêutico , Endometriose/patologia , Feminino , Humanos , Inflamação/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/etiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Transdução de SinaisRESUMO
Increased insulin resistance and inflammatory action are observed in pregnancy-induced hypertension (PIH), but similar insulin resistance is observed also in successful pregnancy. To estimate insulin resistance and inflammatory activity in normal pregnancy and PIH, serum concentrations of free fatty acids (FFA; corrected with albumin to estimate unbound FFA), monocyte chemoattractant protein (MCP)-1, and high-molecular weight (HMW) adiponectin were measured in severe PIH patients with a BMI less than 25 kg/m(2) and were measured 3 times during the course of pregnancy in women with normal pregnancies. FFA/albumin, MCP-1, and HMW adiponectin concentrations were significantly higher in PIH patients than in women with normal pregnancies. The 3 measurements of FFA/albumin showed a significant increase through the course of uncomplicated pregnancies. In contrast, MCP-1 and HMW adiponectin were significantly decreased during the course of pregnancy. These results suggest that the reduced MCP-1 concentration in normal pregnancy may be a pathway to inhibit the induction of pathological features from physiological insulin resistance and homeostatic inflammation.
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Quimiocinas/sangue , Ácidos Graxos não Esterificados/sangue , Resistência à Insulina/fisiologia , Adiponectina/sangue , Adulto , Quimiocina CCL2/sangue , Feminino , Humanos , Estudos Longitudinais , GravidezRESUMO
Inflammatory response in preeclampsia (PE) is a key feature in its pathophysiology. Advanced Glycation Endproducts (AGEs), receptors for AGEs (RAGE), and RAGE ligands are involved in systemic inflammation in various pathological conditions. In this study, we measured serum RAGE ligands in normal pregnancy controls and PE patients. Levels of Carboxymethyl Lysine (CML), HMGB1 and S100A12/EN-RAGE were measured in thirty-three normal pregnant women 3 times at 10-12 (1st measurement), 28 (2nd measurement), and 36 (3rd measurement) weeks during gestation for paired analysis. We also measured those in serum samples from 17 severe PE patients at admission using ELISA. Early onset (EO, <32 weeks) and late onset (LO, ≥32 weeks) PE patients were compared with the 2nd and 3rd measurements of normal controls, respectively. CML and HMGB1 did not change during normal pregnancy. However, S100A12/EN-RAGE decreased from the 1st to 2nd measurement (P<0.0001). Across all PE patients, serum CML was unaltered, while HMGB1 significantly increased compared to 2nd (P=0.0002) and 3rd (P<0.0001) measurement as well as individually compared to both EO (P=0.018) and LO groups (P=0.0001). S100A12 in all PE patients increased over 2nd (P=0.0015) and 3rd (P=0.0002) measurements, although only LO was significantly increased compared to the 3rd measurement (P=0.0005). Our data suggest that patterns of serum RAGE ligand concentration indicate different inflammatory pathways in normal pregnancy, EO-PE, and LO-PE.
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Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/imunologia , Receptores Imunológicos/imunologia , Adulto , Biomarcadores/sangue , Progressão da Doença , Feminino , Seguimentos , Proteína HMGB1/sangue , Humanos , Inflamação/sangue , Inflamação/imunologia , Mediadores da Inflamação/sangue , Ligantes , Lisina/análogos & derivados , Lisina/sangue , Gravidez , Trimestres da Gravidez , Receptor para Produtos Finais de Glicação Avançada , Proteínas S100/sangue , Proteína S100A12RESUMO
PROBLEM: Preeclampsia, a pregnancy-related hypertensive disorder, is one of the leading causes of fetal and maternal death globally. Angiogenic factors including vascular endothelial growth factor (VEGF) are involved in the formation of new blood vessels required for placental development and function. The hallmark of preeclampsia is similar to the toxicities related to antiangiogenesis therapy. VEGF inhibitors or antagonists promote vasoconstriction, hypertension and proteinuria. VEGF plays a role in attenuating hypertension and improving kidney damage in an animal model; however, the mechanisms underlying this effect remain poorly defined. The aim of this paper is to summarize recent advances in VEGF-mediated signaling and the target molecules, and provide new insights into treatment strategies for preeclampsia. METHOD OF STUDY: This article reviews the English-language literature for pathogenesis of preeclampsia based on VEGF signaling and hypertension. RESULTS: VEGF activates downstream signaling molecules, including Ca(2+)/CAMKK, Rac1/NOX, ROS/ERK, Ezrin/Calpain/PI3K/Akt, PLCγ/PKC and Src/HSP90. Among these signalings, important pathways for receptor-triggered intracellular signaling are (1) the PI3K/Akt-dependent, (2) the PLCγ-dependent and (3) the ERK/Egr-1-dependent pathway. VEGF is closely involved in receptor-activated signaling events, leading to eNOS-dependent NO synthesis and eNOS-independent endothelial cell proliferation, respectively, and thus modulates vasoactive function and angiogenic response. CONCLUSION: This review highlights the potential role of NO in vasodilation, while stress-related ERK activation might act to strengthen angiogenesis, migration and proliferation. We discuss the similarity between preeclampsia and VEGF-targeted therapy-induced hypertension.
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Inibidores da Angiogênese/efeitos adversos , Hipertensão/induzido quimicamente , Pré-Eclâmpsia/induzido quimicamente , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/fisiologia , Feminino , Humanos , Hipertensão/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
We report the case of a patient with placenta previa accreta. A 29-year-old multipara, who had previously undergone a cesarean section, was admitted to our hospital for vaginal bleeding. An emergency cesarean section was carried out at the 33rd week of gestation. Uterine bleeding was uncontrollable, and hence, hysterectomy was planned. However, before hysterectomy, B-Lynch brace suture was carried out to control the massive bleeding; moreover, the suturing technique enabled uterine artery embolization to be carried out as an interventional radiological technique. A good postoperative course was observed, and thus, a secondary hysterectomy was not required. A combination of the B-Lynch brace suture technique and uterine artery embolization may be an alternative treatment for emergency bleeding during cesarean section in patients with placenta previa accreta.
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Cesárea/efeitos adversos , Placenta Acreta/cirurgia , Hemorragia Pós-Parto/cirurgia , Técnicas de Sutura , Embolização da Artéria Uterina/métodos , Hemorragia Uterina/cirurgia , Adulto , Feminino , Humanos , Gravidez , Hemorragia Uterina/etiologiaAssuntos
Síndrome de Down/complicações , Medicamentos de Ervas Chinesas/uso terapêutico , Cirrose Hepática/complicações , Transtornos Mieloproliferativos/tratamento farmacológico , Biópsia , Colagogos e Coleréticos , Diagnóstico Diferencial , Seguimentos , Humanos , Recém-Nascido , Fígado/patologia , Cirrose Hepática/tratamento farmacológico , Masculino , Mielopoese , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/etiologiaRESUMO
PROBLEM: Preeclampsia, a pregnancy-specific hypertensive syndrome, is one of the leading causes of premature births as well as fetal and maternal death. Preeclampsia lacks effective therapies because of the poor understanding of disease pathogenesis. The aim of this paper is to review molecular signaling pathways that could be responsible for the pathogenesis of preeclampsia. METHOD OF STUDY: This article reviews the English-language literature for pathogenesis and pathophysiological mechanisms of preeclampsia based on genome-wide gene expression profiling and proteomic studies. RESULTS: We show that the expression of the genes and proteins involved in response to stress, host-pathogen interactions, immune system, inflammation, lipid metabolism, carbohydrate metabolism, growth and tissue remodeling was increased in preeclampsia. Several significant common pathways observed in preeclampsia overlap the datasets identified in TLR (Toll-like receptor)- and RAGE (receptor for advanced glycation end products)-dependent signaling pathways. Placental oxidative stress and subsequent chronic inflammation are considered to be major contributors to the development of preeclampsia. CONCLUSION: This review summarizes recent advances in TLR- and RAGE-mediated signaling and the target molecules, and provides new insights into the pathogenesis of preeclampsia.
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Inflamação/metabolismo , Pré-Eclâmpsia/etiologia , Receptores de Reconhecimento de Padrão/metabolismo , Animais , Feminino , Perfilação da Expressão Gênica , Humanos , Inflamação/genética , Ligantes , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Gravidez , ProteômicaRESUMO
Endometriosis affects an estimated 10% of women in the reproductive-age group. Here, we review current knowledge on molecular genesis of endometriosis-associated epithelial ovarian carcinoma (EOC). This article reviews the English language literature for biology, pathogenesis, and pathophysiological studies on endometriosis-associated EOC. Although endometriosis generally remains a benign condition, it demonstrates somatically acquired genetic alterations. Clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) are the most frequent types of EOC associated with endometriosis. Retrograde menstruation or ovarian hemorrhage carries highly pro-oxidant factors, such as iron, into the peritoneal cavity or ovarian endometrioma. CCC and EAC should be considered separately in studies of endometriosis-associated EOC. The repeated events of hemorrhage in endometriosis can contribute to carcinogenesis and progression via 3 major processes: 1) increasing oxidative stress promotes DNA methylation; 2) activating anti-apoptotic pathways supports tumor promotion; and 3) aberrant expression of stress signaling pathways contributes to tumor progression. This review summarizes recent advances in the understanding of epidemiology, carcinogenesis, pathogenesis, and pathophysiology of endometriosis-associated EOC; and a possible novel model is proposed.
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Carcinoma/genética , Carcinoma/fisiopatologia , Endometriose/complicações , Endometriose/fisiopatologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/fisiopatologia , Carcinoma/etiologia , Metilação de DNA/fisiologia , Feminino , Genes do Tumor de Wilms , Genes ras/genética , Hemorragia/etiologia , Hemorragia/fisiopatologia , Fator 1 Nuclear de Hepatócito/genética , Humanos , Perda de Heterozigosidade , Repetições de Microssatélites/genética , Biologia Molecular , Neoplasias Ovarianas/etiologia , Estresse Oxidativo/fisiologia , PTEN Fosfo-Hidrolase/genética , Receptores de Estrogênio/genética , Fatores de Risco , Transdução de Sinais/fisiologia , Estresse Fisiológico/fisiologiaRESUMO
Recent data have provided information regarding the profiles of clear cell carcinoma of the ovary (CCC) with adenine-thymine rich interactive domain 1A (ARID1A) mutations. The purpose of this review was to summarize current knowledge regarding the molecular mechanisms involved in CCC tumorigenesis and to describe the central role played by the aberrant chromatin remodeling. The present article reviews the English-language literature for biochemical studies on the ARID1A mutation and chromatin remodeling in CCC. ARID1A is responsible for directing the SWI/SNF complex to target promoters and regulates the transcription of certain genes by altering the chromatin structure around those genes. The mutation spectrum of ARID1A was enriched for C to T transitions. CCC and clear cell renal cell carcinoma (ccRCC) resemble each other pathogenetically. Dysfunction of the ARID1A protein, which occurs with VHL mutations in ccRCC, is responsible for loss of the assembly of the ARID1A-mediated histone H2B complex. Therefore, ARID1A acts as a chromatin remodeling modifier, which stimulates cell signaling that can lead to cell cycle arrest and cell death in the event of DNA damage. The dysfunction of ARID1A may result in susceptibility to CCC carcinogenesis through a defect in the repair or replication of damaged DNA.