RESUMEN
The narrative review article is focused on the strengths and limitations of modern imaging methods in the preoperative differential diagnosis of uterine mesenchymal tumours. In order to tailor the surgical procedures, imaging methods, namely ultrasound and magnetic resonance imaging (MRI), should be taken into account as well as clinical symptoms, age, and fertility plans. On ultrasound scans, uterine sarcomas have the appearance of large, usually solitary tumours of non-homogenous structure with irregular cysts, ill-defined outline borders (interrupted capsule), absence of calcifications with acoustic shadowing, and moderate to rich internal vascularisation. Rapid growth between follow-ups or atypical growth in peri- or post-menopause is also a sign of malignancy. On MRI, uterine sarcomas are characterized by irregular borders, hyperintense areas on T1-weighted and T2- weighted images, and central non-enhancing necrotic areas. On diffusion-weighted imaging (DWI/MRI), sarcomas exhibit markedly restricted diffusion but there is a significant overlap with some variants of fibroids. Core-needle or hysteroscopic biopsy can be used preoperatively if suspicious features are detected on ultrasound or MRI scans, particularly before myomectomy if fertility preservation is required or when conservative management is considered in asymptomatic women. Other imaging methods, such as positron emission tomography fused with CT (PET-CT) or computed tomography (CT) have limited role to distinguish uterine sarcomas from myomas and are suitable only for staging purposes. The importance of tumour markers including lactate dehydrogenase in preoperative work-up have not been verified yet. Conclusion: Uterine sarcomas can be distinguished from much more common myomas based on a combination of malignant features on ultrasound or MR imaging. In these suspicious cases the type and extent of surgery should be adjusted, avoiding intraperitoneal morcellation, which could lead to iatrogenic tumour spread and worsening of the patient's prognosis.
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Sarcoma , Neoplasias Uterinas , Humanos , Femenino , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/patología , Sarcoma/diagnóstico , Sarcoma/diagnóstico por imagen , Sarcoma/cirugía , Diagnóstico Diferencial , Leiomioma/diagnóstico , Leiomioma/diagnóstico por imagen , Leiomioma/cirugía , Ultrasonografía/métodos , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: The addition of trabectedin to doxorubicin, followed by trabectedin maintenance, may have superior efficacy to doxorubicin alone as first-line treatment in patients with advanced leiomyosarcoma. METHODS: We conducted a phase 3 trial involving patients with metastatic or unresectable leiomyosarcoma who had not received chemotherapy previously. Patients were randomly assigned to receive either single-agent doxorubicin (six cycles) or doxorubicin plus trabectedin (six cycles), with continued trabectedin as maintenance therapy in patients in the doxorubicin-trabectedin group who did not have disease progression. Surgery to resect residual disease was allowed in each group after six cycles of therapy. Analyses of progression-free survival (primary end point) and overall survival (secondary end point) were adjusted for two stratification factors: tumor origin site (uterine vs. soft tissue) and disease stage (locally advanced vs. metastatic). The primary end-point results were reported previously. RESULTS: A total of 150 patients underwent randomization. At a median follow-up of 55 months (interquartile range, 49 to 63), a total of 107 patients had died (47 in the doxorubicin-trabectedin group and 60 in the doxorubicin group). The median overall survival was longer in the doxorubicin-trabectedin group (33 months; 95% confidence interval [CI], 26 to 48) than in the doxorubicin group (24 months; 95% CI, 19 to 31); the adjusted hazard ratio for death was 0.65 (95% CI, 0.44 to 0.95). In a finding consistent with earlier reports, progression-free survival was longer in the doxorubicin-trabectedin group (12 months; 95% CI, 10 to 16) than in the doxorubicin group (6 months; 95% CI, 4 to 7); the adjusted hazard ratio for progression or death was 0.37 (95% CI, 0.26 to 0.53). The incidence of adverse events and the percentage of patients with dose reductions were higher with doxorubicin plus trabectedin than with doxorubicin alone. CONCLUSIONS: Combination therapy with doxorubicin and trabectedin induction, followed by trabectedin maintenance, was associated with improved overall survival and progression-free survival, as compared with doxorubicin alone, among patients with metastatic or surgically unresectable uterine or soft-tissue leiomyosarcoma. (Funded by PharmaMar and others; LMS04 ClinicalTrials.gov number, NCT02997358.).
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Protocolos de Quimioterapia Combinada Antineoplásica , Doxorrubicina , Leiomiosarcoma , Neoplasias de los Tejidos Blandos , Trabectedina , Neoplasias Uterinas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Estimación de Kaplan-Meier , Leiomiosarcoma/tratamiento farmacológico , Leiomiosarcoma/mortalidad , Leiomiosarcoma/patología , Quimioterapia de Mantención , Supervivencia sin Progresión , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/patología , Análisis de Supervivencia , Trabectedina/administración & dosificación , Trabectedina/efectos adversos , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/mortalidad , Neoplasias Uterinas/patología , Estadificación de NeoplasiasRESUMEN
Emerging evidence suggests a tentative association between cathepsins and uterine leiomyoma (UL). Previous investigations have predominantly focused on the role of cathepsins in the metastasis and colonization of gynecological malignancies. Still, observational studies may lead to confounding and biases. We employed a bidirectional Mendelian randomization (MR) analysis to elucidate the causative links between various cathepsins and UL. Instrumental variables (IVs) of cathepsins and UL within the European cohort were from extant genome-wide association study datasets. Sensitivity assessments was executed, and the heterogeneity of the findings was meticulously dissected to affirm the solidity of the outcomes. Our findings reveal the association between cathepsin B (CTSB) and an elevated risk of developing UL (all cancers excluded) [Inverse Variance Weighted (IVW) method]: OR = 1.06, 95%CI [1.02, 1.11], P = 0.008895711. Although the association does not persist after multiple testing or Steiger filtering, this finding adds to our understanding of the causal relationship between CTSB of various cathepsins and UL (all cancers excluded) and may herald new therapeutic avenues for individuals affected by this condition.
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Catepsina B , Catepsinas , Estudio de Asociación del Genoma Completo , Leiomioma , Análisis de la Aleatorización Mendeliana , Neoplasias Uterinas , Humanos , Femenino , Leiomioma/genética , Leiomioma/patología , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Catepsina B/genética , Catepsina B/metabolismo , Catepsinas/genética , Catepsinas/metabolismo , Polimorfismo de Nucleótido Simple , Predisposición Genética a la EnfermedadRESUMEN
Over 70% of leiomyoma (LM) harbor MED12 mutations, primarily in exon 2 at c.130-131 (GG). Myometrial cells are the cell origin of leiomyoma, but the MED12 mutation status in non-neoplastic myometrial cells is unknown. In this study, we investigated the mutation burden of MED12 in myometrium. As traditional Sanger or even NGS sequencing may not be able to detect MED12 mutations that are lower than 0.1% in the testing sample, we used duplex deep sequencing analysis (DDS) to overcome this limitation. Tumor-free myometria (confirmed by pathology evaluation) were dissected, and genomic DNA from MED12 exon 2 (test) and TP53 exon 5 (control) were captured by customer-designed probe sets, followed by DDS. Notably, DDS demonstrated that myometrial cells harbored a high frequency of mutations in MED12 exon 2 and predominantly in code c.130-131. In contrast, the baseline mutations in other coding sequences of MED12 exon 2 as well as in the TP53 mutation hotspot, c.477-488 were comparably low in myometrial cells. This is the first report demonstrating a non-random accumulation of MED12 mutations at c.130-131 sites in non-neoplastic myometrial cells which provide molecular evidence of early somatic mutation events in myometrial cells. This early mutation may contribute to the cell origin for uterine LM development in women of reproductive age.
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Complejo Mediador , Mutación , Miometrio , Humanos , Femenino , Miometrio/metabolismo , Miometrio/patología , Complejo Mediador/genética , Complejo Mediador/metabolismo , Mutación/genética , Exones/genética , Leiomioma/genética , Leiomioma/patología , Persona de Mediana Edad , Adulto , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Uterine leiomyosarcoma (uLMS) is the most common type of uterine sarcoma, associated with poor prognosis, high rates of recurrence, and metastasis. Currently, the molecular mechanism of the origin and development of uLMS is limited. Bromodomain and extra-terminal (BET) proteins are involved in both physiological and pathological events. However, the role of BET proteins in the pathogenesis of uLMS is unknown. Here, we show for the first time that BET protein family members, BRD2, BRD3, and BRD4, are aberrantly overexpressed in uLMS tissues compared to the myometrium, with a significant change by histochemical scoring assessment. Furthermore, inhibiting BET proteins with their small, potent inhibitors (JQ1 and I-BET 762) significantly inhibited the uLMS proliferation dose-dependently via cell cycle arrest. Notably, RNA-sequencing analysis revealed that the inhibition of BET proteins with JQ1 and I-BET 762 altered several critical pathways, including the hedgehog pathway, EMT, and transcription factor-driven pathways in uLMS. In addition, the targeted inhibition of BET proteins altered several other epigenetic regulators, including DNA methylases, histone modification, and m6A regulators. The connections between BET proteins and crucial biological pathways provide a fundamental structure to better understand uterine diseases, particularly uLMS pathogenesis. Accordingly, targeting the vulnerable epigenome may provide an additional regulatory mechanism for uterine cancer treatment.
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Leiomiosarcoma , Factores de Transcripción , Neoplasias Uterinas , Humanos , Femenino , Leiomiosarcoma/metabolismo , Leiomiosarcoma/patología , Leiomiosarcoma/genética , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patología , Neoplasias Uterinas/genética , Factores de Transcripción/metabolismo , Proliferación Celular , Azepinas/farmacología , Regulación Neoplásica de la Expresión Génica , Triazoles/farmacología , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Epigénesis Genética , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/genética , Persona de Mediana Edad , Proteínas que Contienen Bromodominio , Benzodiazepinas , ProteínasRESUMEN
OBJECTIVES: To investigate the clinicopathological characteristics and prognosis of patients with uterine sarcoma treated following surgery for presumed benign disease. METHODS: We identified all patients with uterine sarcoma found incidentally after primary surgery for presumed benign disease who presented to our institution and received re-exploration for completion surgery from January 1, 2004 to January 1, 2021. We analyzed the clinicopathological characteristics and prognosis. RESULTS: Overall, 95 patients were included in our study. For the initial surgery, myomectomy was performed in 50 (52.6%, 50/95) patients, hysterectomy was performed in 45 (47.4%, 45/95) patients. All patients were re-explored to complete the staging operation. The median time to the staging surgery was 40 days (range 15-90 days). There were 29 patients (30.5%, 29/95) had remnant sarcomas, with 17 patients (17/95, 17.9%) on the remaining uterus, 9 patients (9/95, 9.5%) had disseminated diseases, and 4 patients (4/95, 4.2%) had positive lymph nodes. About 40 patients (42.1%) received adjuvant chemotherapy, 55.2% (16/29) and 36.4% (24/66) patients with/without remnant diseases received adjuvant chemotherapy, respectively (P = 0.087). The median follow-up duration was 76.7 months (IQR: 34.8-118.1 months). And 17 patients (17.9%) had recurrence following re-exploration surgery. 5-year progression-free survival (PFS) and 5-year overall survival (OS) for the entire cohort was 81.7% and 92.1%, respectively. Patients with remnant sarcomas had a tendency towards a worse 5-year PFS and 5-year OS, compared with those without (5-year PFS: 75.6% vs. 84.5%, P = 0.224; 5-year OS: 85.5% vs. 95.1%, P = 0.217). Patients with disseminated diseases had a worse 5-year OS (62.5% vs. 95.1%, P = 0.007) and non-significantly worse 5-year PFS (64.8% vs. 83.4%, P = 0.153) compared with those without. CONCLUSIONS: Patients with uterine sarcoma treated following surgery for presumed benign disease have a favorable survival. Patients with disseminated diseases had a worse 5-year OS compared with those without. Surgical re-exploration may be valuable for removing remnant sarcomas and disseminated diseases.
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Histerectomía , Sarcoma , Neoplasias Uterinas , Humanos , Femenino , Persona de Mediana Edad , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/patología , Neoplasias Uterinas/mortalidad , Adulto , Sarcoma/cirugía , Sarcoma/mortalidad , Sarcoma/patología , Anciano , Pronóstico , Estudios Retrospectivos , Estadificación de Neoplasias , Quimioterapia Adyuvante , Miomectomía Uterina , Análisis de SupervivenciaRESUMEN
Uterine fibroids (UFs), the most common tumors in women of reproductive age, are characterized by sex steroid-dependent growth and excessive deposition of extracellular matrix (ECM) surrounding UF smooth muscle cells. Women with symptomatic UFs experience heavy menstrual bleeding and consequent iron-deficiency anemia. They also have a risk of recurrent pregnancy loss, preterm birth, and cesarean delivery, indicating that UFs can negatively affect reproductive outcomes. Various types of immune cells, including innate and adaptive cells, are observed in UFs; however, the impact of these cells on the pathophysiology of UFs remains unclear. Inflammation may play important roles in the growth of UFs, and expression levels of proinflammatory and inflammatory cytokines, such as interleukin (IL)-1, IL-6, IL-10, TNF-α, and TGF-ß, are upregulated in UFs. These cytokines play important roles in the interaction between growth factors and ECM that is regulated by the sex steroids estrogen and progesterone. Furthermore, proinflammatory mediators are upregulated in females with UFs, with higher expression levels in the endometrium with submucosal and intramural UFs than in the endometrium without UFs, indicating that these proinflammatory cytokines may impair endometrial receptivity, leading to implantation failure in in vitro fertilization programs. Hormonal treatments using gonadotropin releasing hormone analogs and the selective progesterone receptor modulator ulipristal acetate significantly shrink UFs and improve UF-related symptoms. These compounds can regulate local inflammation in UFs and adjacent myometrium. Controlling and improving local inflammation caused by UFs may represent a novel therapeutic strategy for UFs and potentially improve reproductive outcomes in women with symptomatic UFs.
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Inflamación , Leiomioma , Humanos , Femenino , Leiomioma/inmunología , Leiomioma/patología , Embarazo , Inflamación/inmunología , Citocinas/metabolismo , Neoplasias Uterinas/inmunología , Neoplasias Uterinas/patología , Endometrio/inmunología , Endometrio/patología , Mediadores de Inflamación/metabolismoRESUMEN
BACKGROUND: Angioleiomyoma, a benign tumour composed of smooth muscle cells and thick-walled vessels, is expected to be very rare in the female genital tract. This study aimed to describe the clinicopathological features and treatment outcomes of angioleiomyoma in the female genital tract. METHODS: We retrospectively reviewed 89 women with angioleiomyoma in the genital tract who were treated at Third Xiangya Hospital of Central South University between July 2008 and October 2023. Symptom remission rate was the primary outcome of the study. RESULTS: Angioleiomyomas accounted for 0.6% of leiomyomas of the female genital tract. The average age of the 89 women was 41.8 ± 8.7 years. Seventy women (78.7%) had a history of uterine surgery, of whom two patients had removed uterine angioleiomyoma by laparoscopic myomectomy. The angioleiomyomas of 61 (68.5%) women were located in the uterine corpus, 17 (19.1%) in the broad ligament, 10 (11.2%) in the cervix and only 1 (1.1%) in the vagina. Abnormal uterine bleeding was the main clinical manifestation of angioleiomyomas located in the uterine corpus or cervix, whereas the main clinical manifestation of angioleiomyomas in the broad ligaments was pelvic mass. Of the 89 women, 59 underwent surgery to preserve the uterus, and 30 underwent total hysterectomy or subtotal hysterectomy. The intraoperative blood loss was more than 500 ml (700-4,500 ml) in six women. The symptom remission rate was 100% after surgery. Among the 59 women with preserved uterus, 8 showed multiple uterine leiomyomas during follow-up, but it was difficult to determine whether they were angioleiomyomas. Angioleiomyomas recurred in one women who underwent total hysterectomy. CONCLUSION: Angioleiomyoma is rare in the female reproductive tract, and patients may present with diverse symptoms, which are related to the location of the tumour. Hysterectomy and myomectomy are both effective treatment methods, but the risk of intraoperative bleeding should be recognised for multiple lesions and those with large diameters. Relapse may occur in some patients.
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Angiomioma , Humanos , Femenino , Estudios Retrospectivos , Adulto , Angiomioma/cirugía , Angiomioma/patología , Persona de Mediana Edad , Resultado del Tratamiento , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/patología , Neoplasias de los Genitales Femeninos/cirugía , Neoplasias de los Genitales Femeninos/patología , Estudios de Cohortes , Histerectomía/métodos , Histerectomía/estadística & datos numéricosRESUMEN
PURPOSE: Uterine serous carcinoma (USC) is a highly aggressive and frequently recurring subtype of endometrial cancer with limited treatment options for advanced or recurrent stages. Sulindac, a classic non-steroidal anti-inflammatory drug, has demonstrated anti-tumor activity in several pre-clinical tumor models. This study aims to evaluate the effect of sulindac on cell proliferation and invasion in USC cells. METHODS: Human USC cell lines ARK-1 and SPEC2 were treated with different concentrations of sulindac. Cell proliferation was assessed using MTT and colony formation assays. ELISA assays measured cellular stress, cleaved caspase 3 activity, antioxidant ability, and adhesion. Cell cycle arrest was evaluated by Cellometer. The invasive capability was detected by wound healing assay. Western blotting was used to analyze the changes in protein expression induced by sulindac. RESULTS: Exposure to sulindac decreased cellular viability in a dose-dependent manner in ARK-1 and SPEC2 cells. Sulindac effectively inhibited cell cycle progression, increased cellular stress, caused apoptosis, and reduced cell adhesion and invasion in USC cells. Additionally, sulindac decreased the expression of COX-2 and blocked phosphorylation of NF-κB induced by TNF-α. CONCLUSION: Sulindac is a potential therapeutic agent for USC that deserves further exploration in pre-clinical studies and potentially future clinical trials.
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Apoptosis , Proliferación Celular , Cistadenocarcinoma Seroso , Sulindac , Neoplasias Uterinas , Humanos , Femenino , Sulindac/farmacología , Proliferación Celular/efectos de los fármacos , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/patología , Línea Celular Tumoral , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/metabolismo , Apoptosis/efectos de los fármacos , Invasividad Neoplásica , Adhesión Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacosRESUMEN
Gestational trophoblastic diseases (GTDs) encompass a spectrum of conditions characterized by abnormal trophoblastic cell growth, ranging from benign molar pregnancies to malignant trophoblastic neoplasms. This systematic review explores the molecular underpinnings of GTDs, focusing on genetic and epigenetic factors that influence disease progression and clinical outcomes. Based on 71 studies identified through systematic search and selection criteria, key findings include dysregulations in tumor suppressor genes such as p53, aberrant apoptotic pathways involving BCL-2 (B-cell lymphoma), and altered expression of growth factor receptors and microRNAs (micro-ribose nucleic acid). These molecular alterations not only differentiate molar pregnancies from normal placental development but also contribute to their clinical behavior, from benign moles to potentially malignant forms. The review synthesizes insights from immunohistochemical studies and molecular analyses to provide a comprehensive understanding of GTD pathogenesis and implications for personalized care strategies.
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Mola Hidatiforme , Humanos , Mola Hidatiforme/genética , Mola Hidatiforme/patología , Mola Hidatiforme/metabolismo , Embarazo , Femenino , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Neoplasias Uterinas/metabolismo , Epigénesis GenéticaRESUMEN
BACKGROUND Perivascular epithelioid cell tumor (PEComa) is usually a benign perivascular tumor that expresses both melanocytic and myogenic cell markers. We report 2 cases of advanced malignant uterine perivascular epithelioid cell tumor (PEComa) in a 74-year-old woman and a 50-year-old woman undergoing surgery in our center. CASE REPORT Case 1: A 74-year-old woman presented with a painful and massive abdominal mass. The imaging revealed a 19-cm necrotic mass close to the mesentery, a suspicious lesion in the uterus, and a probable liver metastasis. The pathological diagnosis was quite difficult with mixed features of leiomyosarcoma and PEComa with an uncommon immunohistochemistry staining pattern. Therefore, we gave a diagnosis of sarcoma with PEComa-like features. Case 2: A 50-year-old woman with metrorrhagia and abdominal pain. Imaging revealed a 7-cm mass in the uterus and suspicious metastatic lesions in the lung and the liver. The immunohistochemistry pattern was typical, with a strong positivity of Human Melanoma Black-45 (HMB-45) and focal positivity of H-Caldesmon. The patient benefited from targeted adjuvant therapy (MTOR inhibitor-based), with 8-month a follow-up showing no recurrence for this Grade IV PEComa mutated for TP53, ATRX, and TSC1. CONCLUSIONS We have report 2 cases of metastatic PEComa with different clinicopathological features. An overlap remains between characteristics of PEComas and smooth-muscle tumors. At present, there are no known pathognomonic findings or specific diagnostic markers.
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Neoplasias de Células Epitelioides Perivasculares , Neoplasias Uterinas , Humanos , Femenino , Neoplasias de Células Epitelioides Perivasculares/diagnóstico , Neoplasias de Células Epitelioides Perivasculares/secundario , Neoplasias de Células Epitelioides Perivasculares/patología , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/patología , Persona de Mediana Edad , Anciano , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/diagnóstico , Diagnóstico Diferencial , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundarioRESUMEN
Significant racial disparities exist between Black and White patients with uterine serous carcinoma (USC). While the reasons for these disparities are unclear, several studies have demonstrated significantly different rates of driver mutations between racial groups, including TP53. However, limited research has investigated the transcriptional differences of tumors or the composition of the tumor microenvironment (TME) between these groups. Here, we report the single-nuclei RNA-sequencing profiles of primary USC tumors from diverse racial backgrounds. We find that there are significant differences between the tumors of Black and White patients. Tumors from Black patients exhibited higher expression of specific genes associated with aggressiveness, such as PAX8, and axon guidance and synaptic signaling pathways. We also demonstrated that T cell populations are reduced in the tumor tissue compared to matched benign, while anti-inflammatory macrophage populations are retained within the TME. Furthermore, we investigated the connection between PAX8 overexpression and immunosuppression in USC through regulation of several cytokines and chemokines. Notably, we show that PAX8 activity can influence macrophage gene expression and protein secretion. These studies provide a detailed understanding of the USC transcriptome and TME, and identify differences in tumor biology from patients of different racial backgrounds.
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Factor de Transcripción PAX8 , Transducción de Señal , Microambiente Tumoral , Neoplasias Uterinas , Humanos , Femenino , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Factor de Transcripción PAX8/genética , Factor de Transcripción PAX8/metabolismo , Transducción de Señal/genética , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/inmunología , Regulación Neoplásica de la Expresión Génica , Población Blanca/genética , Análisis de la Célula Individual , Persona de Mediana EdadRESUMEN
Endometrial cancer, including high-grade subtypes, has a rising incidence and mortality. Uterine serous carcinoma (USC) and uterine carcinosarcoma (UCS) make up a small but increasing proportion of endometrial cancer cases and account for a significant portion of endometrial cancer mortality. Despite being molecularly and clinically distinct, both USC and UCS have a poor prognosis. Thus far, there have been few therapeutic strategies directed at these endometrial cancer subtypes. This review summarizes the genomic and molecular features of USC and UCS, clinical advances in the treatment of primary advanced and recurrent endometrial cancer, and novel molecularly-driven treatment strategies.
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Carcinosarcoma , Cistadenocarcinoma Seroso , Neoplasias Uterinas , Humanos , Femenino , Carcinosarcoma/terapia , Carcinosarcoma/genética , Carcinosarcoma/patología , Carcinosarcoma/diagnóstico , Neoplasias Uterinas/genética , Neoplasias Uterinas/terapia , Neoplasias Uterinas/patología , Cistadenocarcinoma Seroso/terapia , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/diagnóstico , Pronóstico , Terapia Molecular DirigidaRESUMEN
OBJECTIVE: To assess the efficacy of mechanical resection through TruClear™ hysteroscopy in patients with endometrial polyps and submucosal fibroids. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Obstetrics and Gynaecology, Shifa International Hospital, Islamabad, Pakistan, from June 2018 to 2022. METHODOLOGY: Patients diagnosed with endometrial polyps and submucosal fibroids confirmed by abdominal or transvaginal ultrasonography were included. Patients having a history of congestive cardiac failure, chronic kidney disease, and bleeding diathesis were excluded from the study. Data about the complete removal of pathology (endometrial polyps and submucosal fibroids), mean operating time, and postoperative complications such as bleeding and perforation were extracted. The follow-up was set up to 6 months after the procedure. RESULTS: The average age of the 45 patients was 35.62 ± 7.46 years. Heavy menstrual bleeding was the most prevalent symptom, seen in 73.3% of cases, followed by irregular vaginal bleeding (IVB) in 11.1% of cases. The most frequent disease identified by sonography was a polyp in 21 (47%) instances, followed by submucosal fibroids in 12 (27%) cases, mixed pathology in 10 (22%), and malignancy in 2 (4%) cases. The overall average operative time was 36.46 ± 24.94 minutes. A hundred percent removal of lesions was observed in this study. Persistent symptoms were observed in 13% of patients after the surgery so they were treated with other interventions. The most common intervention was an intrauterine hormonal device. Intraoperative bleeding was observed in only one patient and was managed by intraoperative intrauterine balloon insertion. The recurrence rate was 8.9% (4/45). CONCLUSION: TruClear™ hysteroscopy showed a major advantage in the successful and complete removal of the pathology, low operation time, and complications. KEY WORDS: Fibroids, Hysteroscopy, Polyps, Endometrial resection, Menstrual bleeding.
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Histeroscopía , Leiomioma , Pólipos , Neoplasias Uterinas , Humanos , Femenino , Histeroscopía/métodos , Leiomioma/cirugía , Leiomioma/patología , Pólipos/cirugía , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/patología , Pakistán/epidemiología , Tempo Operativo , Menorragia/cirugía , Enfermedades Uterinas/cirugía , Complicaciones Posoperatorias/epidemiología , Hemorragia Uterina/cirugíaRESUMEN
BACKGROUND: Patients with choriocarcinoma (CC) accompanying chemoresistance conventionally present a poor prognosis. Whether ras protein activator like-1 (RASAL1) functions as a tumor promoter or suppressor depends on tumor types. However, the role of RASAL1 in process of chemoresistance of CC and underlying molecular mechanism remain elusive. METHODS: The expression pattern of RASAL1 in CC cells and tissues was measured using Western blotting, immunohistochemistry and qRT-PCR. Cell viability and proliferative ability were assessed by MTT assay, Tunnel assay and flow cytometric analysis. Additionally, the stemness was evaluated by the colony formation and tumor sphere formation. Methotrexate (MTX) was applied to exam the chemosensitivity of CC cells. RESULTS: The expression of RASAL1 was reduced both at the protein and mRNA levels in CC tissues and cells compared to hydatidiform mole (HM) and invasive mole (IM). Loss of RASAL1 was attributed to its promoter hypermethylation and could be restored by 5-Aza. Knock-down of RASAL1 promoted the viability, proliferative potential, stemness and EMT phenotype of JEG-3 cells. However, induced overexpression of RASAL1 by 5-Aza significantly prohibited cell proliferation and stemness potential of the JAR cell. Additionally, the xenograft model indicated that knockdown of RASAL1 led to a remarkable increase of tumor volume and weight in comparison with its counterpart. Moreover, the stimulatory activity brought by decrease of RASAL1 could be deprived by ß-catenin inhibitor XAV 939, yet the suppressive activity resulted from its promoter demethylation could be rescued by ß-catenin activator BML-284, indicating that function of RASAL1 depends on ß-catenin. Besides, the co-immunoprecipitation assay confirmed the physical binding between RASAL1 and ß-catenin. Further investigations showed hypermethylated RASAL1 was regulated by TET2 but not DNMTs. CONCLUSION: Taken together, the present data elucidated that reduced RASAL1 through its promoter hypermethylation regulated by TET2 promoted the tumorigenicity and chemoresistance of CC via modulating ß-catenin both in vitro and in vivo.
Asunto(s)
Coriocarcinoma , Metilación de ADN , Proteínas de Unión al ADN , Dioxigenasas , Resistencia a Antineoplásicos , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas , Animales , Femenino , Humanos , Ratones , Embarazo , Carcinogénesis/genética , Línea Celular Tumoral , Proliferación Celular , Coriocarcinoma/metabolismo , Coriocarcinoma/patología , Coriocarcinoma/genética , Dioxigenasas/metabolismo , Dioxigenasas/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/genética , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Neoplasias Uterinas/metabolismoRESUMEN
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is an autosomal-dominant disorder that results from a germline pathogenic variant in the fumarate hydratase (FH) gene on chromosome 1, characterised by renal cell carcinoma (RCC), cutaneous leiomyoma and uterine leiomyoma. Leiomyosarcomas are reported in less than 1% of those with HLRCC. We report a case of a man in his 30s who had a long-standing plaque excised from the left upper arm after undergoing a radical nephrectomy for a fumarate-deficient RCC, with histological exam revealing a grade 1 leiomyosarcoma. Genetic testing confirmed a heterozygous pathogenic variant in the FH gene. This is a rare case of leiomyosarcoma associated with HLRCC, and our patient remains under surveillance with interval abdominal imaging and skin examination. Leiomyosarcomas are difficult to distinguish clinically from their benign counterpart; therefore, histopathological examination is paramount with a low threshold for excision.
Asunto(s)
Fumarato Hidratasa , Leiomiomatosis , Leiomiosarcoma , Síndromes Neoplásicos Hereditarios , Neoplasias Cutáneas , Neoplasias Uterinas , Humanos , Leiomiomatosis/genética , Leiomiomatosis/patología , Leiomiomatosis/cirugía , Leiomiomatosis/diagnóstico , Masculino , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Leiomiosarcoma/genética , Leiomiosarcoma/diagnóstico , Leiomiosarcoma/cirugía , Leiomiosarcoma/patología , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/cirugía , Síndromes Neoplásicos Hereditarios/patología , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirugía , Adulto , Fumarato Hidratasa/genética , Nefrectomía , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/diagnóstico , Neoplasias Renales/cirugíaRESUMEN
PURPOSE: This study was presented to investigate the clinical-pathological characteristics of gestational trophoblastic neoplasia (GTN) following non-molar pregnancy and differentiated with ectopic pregnancy (EP). METHODS: The clinical data of 83 patients who were admitted for suspected GTN after non-molar pregnancy at the Women's Hospital School of Medicine Zhejiang University from January 2015 to September 2022 were selected for analysis. RESULTS: In total, 41 cases were confirmed non-molar GTN, including 31 choriocarcinoma, 9 PSTT (placental site trophoblastic tumor), and 1 ETT (epithelioid trophoblastic tumor), while 42 cases were confirmed EP. Compared with ectopic pregnancy, non-molar GTN patients had lower levels of serum progesterone compared with EP (3.81 nmol/L vs 17.70 nmol/L, P = 0.001). Based on the ultrasound, the thickness of the endometrium was thinner in patients with non-molar GTN compared with EP (0.565 cm vs 0.70 cm, P = 0.018). By histopathologic examination, the endothelium of non-molar GTN showed less decidual-like changes compared with EP (64.3% vs 14.6%, P = 0.001). CONCLUSION: A combination of serum progesterone levels, endometrium thickness, and histopathologic features of the endometrium can help to differentiate non-molar GTN and EP. Surgeries including hysteroscopy with curettage and/or laparoscopy are needed.
Asunto(s)
Enfermedad Trofoblástica Gestacional , Embarazo Ectópico , Progesterona , Humanos , Femenino , Embarazo , Adulto , Diagnóstico Diferencial , Enfermedad Trofoblástica Gestacional/sangre , Enfermedad Trofoblástica Gestacional/patología , Enfermedad Trofoblástica Gestacional/diagnóstico , Embarazo Ectópico/sangre , Embarazo Ectópico/diagnóstico , Embarazo Ectópico/patología , Progesterona/sangre , Neoplasias Uterinas/patología , Neoplasias Uterinas/sangre , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirugía , Estudios Retrospectivos , Endometrio/patología , Tumor Trofoblástico Localizado en la Placenta/patología , Tumor Trofoblástico Localizado en la Placenta/sangre , Tumor Trofoblástico Localizado en la Placenta/diagnóstico , Tumor Trofoblástico Localizado en la Placenta/cirugía , Ultrasonografía , Persona de Mediana EdadRESUMEN
Pseudo-Meigs syndrome is a rare syndrome characterized by hydrothorax and ascites associated with pelvic masses, and patients occasionally present with elevated serum cancer antigen-125 (CA125) levels. Hydropic leiomyoma (HLM) is an uncommon subtype of uterine leiomyoma characterized by hydropic degeneration and secondary cystic changes. Rapidly enlarging HLMs accompanied by hydrothorax, ascites, and elevated CA125 levels may be misdiagnosed as malignant tumors. Here, we report a case of HLM in a 45-year-old Chinese woman who presented with ascites and hydrothorax. Preoperative abdominopelvic CT revealed a giant solid mass in the fundus uteri measuring 20 × 15 × 12 cm. Her serum CA125 level was elevated to 247.7 U/ml, while her hydrothorax CA125 level was 304.60 U/ml. The patient was initially diagnosed with uterine malignancy and underwent total abdominal hysterectomy and adhesiolysis. Pathological examination confirmed the presence of a uterine hydropic leiomyoma with cystic changes. After tumor removal, the ascites and hydrothorax subsided quickly, with no evidence of recurrence. The patient's serum CA125 level decreased to 116.90 U/mL on Day 7 and 5.6 U/mL on Day 40 postsurgery. Follow-up data were obtained at 6 months, 1 year, and 2 years after surgery, and no recurrence of ascites or hydrothorax was observed. This case highlights the importance of accurate diagnosis and appropriate management of HLM to achieve successful outcomes.