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1.
Virchows Arch ; 478(2): 153-190, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33604759

RESUMO

A European consensus conference on endometrial carcinoma was held in 2014 to produce multidisciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (27 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2014, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 191 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover endometrial carcinoma staging, definition of prognostic risk groups integrating molecular markers, pre- and intra-operative work-up, fertility preservation, management for early, advanced, metastatic, and recurrent disease and palliative treatment. Principles of radiotherapy and pathological evaluation are also defined.


Assuntos
Carcinoma/terapia , Neoplasias do Endométrio/terapia , Oncologia/normas , Biomarcadores Tumorais/genética , Biópsia/normas , Carcinoma/genética , Carcinoma/patologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Medicina Baseada em Evidências/normas , Feminino , Humanos , Técnicas de Diagnóstico Molecular/normas , Estadiamento de Neoplasias/normas , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Resultado do Tratamento
2.
Chirurgia (Bucur) ; 116(1): 109-116, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33638332

RESUMO

Cutaneous metastases from endometrial cancer are rare and unusual. This is the case of a 72 years old female patient, diagnosed in 2018 with G3 endometrial serous carcinoma (ESC). At 18 months from the surgical intervention, the patient developed bilateral inguinal lymph nodes metastases and skin secondary lesions; histological and immunohistochemical tests were performed. Computed tomography scan did not indicate visceral secondary lesions, local or regional relapses. We present the treatment practiced, the case's evolution and we discuss about epidemiology, molecular biology, treatment options and management of advanced and local lesions. The appearance of skin metastases in theses cases is associated with poor prognosis and treatment options are limited to palliative chemotherapy and radiotherapy.


Assuntos
Neoplasias do Endométrio , Linfonodos , Neoplasias Cutâneas , Adulto , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Virilha , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Cuidados Paliativos , Neoplasias Cutâneas/secundário , Neoplasias Cutâneas/terapia , Resultado do Tratamento
4.
Anticancer Res ; 41(1): 249-258, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419819

RESUMO

BACKGROUND/AIM: Peritumoral ectopic lymphoid-like structures and tertiary lymphoid structures (TLS), have been identified in various cancers. However, evidence for the role of TLS in endometrial cancer (EC) is lacking. We found a cluster of peritumoral lymphocytes with band-like structures (PLB) in the forefront of EC and analyzed their association with the clinical outcome. MATERIALS AND METHODS: This was a single-center, retrospective cohort study. We evaluated peritumoral lymphoid cells using conventional hematoxylin-eosin and immunohistochemical staining by semi-quantitative digital analysis. RESULTS: A total of 85 cases were included and the presence of PLB was examined. A strong correlation was observed between the density of PLB and progression-free survival (very low, low vs. intermediate, high; HR=0.22; 95%CI=0.093-0.52; p<0.001) and overall survival (very low, low vs. intermediate, high; HR=0.259; 95%CI=0.091-0.73; p=0.011). CONCLUSION: PLB in type II EC show a strong association with fatal outcome.


Assuntos
Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Linfócitos do Interstício Tumoral/patologia , Microambiente Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Terapia Combinada , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/terapia , Feminino , Imunofluorescência , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
5.
Anticancer Res ; 41(2): 937-948, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517300

RESUMO

BACKGROUND/AIM: Most women are managed by a general gynaecologist rather than being centralized in an oncogynaecology unit, resulting in different clinical management. In 2006, a hub & spoke model was introduced in the Provincial Healthcare System of Reggio Emilia, and shared guidelines were written. We aimed to verify the adherence to guidelines and the consequent improvements in quality care. PATIENTS AND METHODS: All patients who underwent a hysterectomy for endometrial cancer in the Reggio Emilia Province hospitals from 2000 to 2016 were included in the study. Clinical and pathological data were carefully recorded for each patient included. RESULTS: This study included 132 and 277 patients in the periods before and after the implementation of the guideline, respectively. In the post-guideline period, the use of hysteroscopy, magnetic resonance, laparoscopy and adjuvant treatment significantly increased. CONCLUSION: Common shared guidelines and a clinical audit can help in improving centralization, resulting in an increased quality of care.


Assuntos
Neoplasias do Endométrio/terapia , Histerectomia/métodos , Qualidade da Assistência à Saúde , Idoso , Quimioterapia Adjuvante , Auditoria Clínica , Feminino , Fidelidade a Diretrizes , Humanos , Histeroscopia , Itália , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto
6.
Support Care Cancer ; 29(1): 311-322, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32358778

RESUMO

PURPOSE: To assess the feasibility and efficacy of a non-hormonal hyaluronic acid (HLA) vaginal gel in improving vulvovaginal estrogen-deprivation symptoms in postmenopausal women with a history of hormone receptor-positive (HR+) cancer. METHODS: For this single-arm, prospective longitudinal trial, we identified disease-free patients with a history of HR+ breast cancer treated with aromatase inhibitors or HR+ endometrial cancer treated with surgery and postoperative radiation. Participants used HLA daily for the first 2 weeks, and then 3×/week until weeks 12-14; dosage was then increased to 5×/week for non-responders. Vulvovaginal symptoms and pH were assessed at 4 time points (baseline [T1], 4-6 weeks [T2], 12-14 weeks [T3], 22-24 weeks [T4]) with clinical evaluation, the Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), Female Sexual Function Index (FSFI), and Menopausal Symptom Checklist (MSCL). RESULTS: Of 101 patients, mean age was 55 years (range, 31-78), 68% (n = 69) were partnered, and 60% (n = 61) were sexually active. In linear mixed models, VAS/VuAS scores significantly improved at all assessment points (all p < 0.001). MSCL scores similarly improved (all p < 0.001). FSFI scores significantly improved from T1 to T2 (p < 0.03), T3 (p < 0.001), and T4 (p < 0.001). Severe vaginal pH (> 6.5) decreased from 26% at T1 to 19% at T4 (p = 0.18). CONCLUSIONS: HLA moisturization improved vulvovaginal health/sexual function of cancer survivors. While HLA administration 1-2×/week is recommended for women in natural menopause, a 3-5×/week schedule appears to be more effective for symptom relief in cancer survivors.


Assuntos
Inibidores da Aromatase/uso terapêutico , Sobreviventes de Câncer , Ácido Hialurônico/uso terapêutico , Vagina/patologia , Doenças Vaginais/tratamento farmacológico , Vulva/patologia , Adulto , Idoso , Atrofia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Pós-Menopausa/fisiologia , Estudos Prospectivos , Cremes, Espumas e Géis Vaginais/uso terapêutico
8.
Bull Cancer ; 107(10): 1006-1018, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-32958220

RESUMO

Endometrial cancer is a common cancer in older women and is often associated with comorbidities. Management of metastatic disease and/or relapse requires a multidisciplinary approach. Recent advances in the understanding of oncogenesis and molecular classification of endometrial cancers offer new therapeutic perspectives. These first recommendations, established following the methodology of Nice-Saint-Paul recommendations for clinical practice (RPC), aims to integrate molecular advances in diagnostic and therapeutic management. In 2020, the histological diagnosis of endometrial cancer is based on morphology and immunohistochemistry, including at least p53, oestrogen and progesterone receptors. Deficiency in the DNA mismatch repair system (MMR) must be assessed in all advanced endometrial tumors for oncogenetic and theranostic purposes. It can be sought initially by an analysis in immunohistochemistry with the 4 markers (MLH1, MSH2, MSH6, PMS2). Medical treatment depends on histological type, presence of hormone receptors and patient's profile to refer to chemotherapy (carboplatin-paclitaxel) or hormone therapy (for example of the progestogen type); in the event of MMR-deficiency, immunotherapy trial is the best option. As part of overall management of advanced endometrial cancer, radiotherapy (and surgery in rare cases) must be discussed, in particular in the event of loco-regional only relapse or oligometastatic disease.


Assuntos
Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/terapia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/terapia , Árvores de Decisões , Neoplasias do Endométrio/secundário , Feminino , Humanos
9.
ESMO Open ; 5(Suppl 3)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32718919

RESUMO

The rapid spread of severe acute respiratory syndrome coronavirus 2 infection and its related disease (COVID-19) has required an immediate and coordinate healthcare response to face the worldwide emergency and define strategies to maintain the continuum of care for the non-COVID-19 diseases while protecting patients and healthcare providers. The dimension of the COVID-19 pandemic poses an unprecedented risk especially for the more vulnerable populations. To manage patients with cancer adequately, maintaining the highest quality of care, a definition of value-based priorities is necessary to define which interventions can be safely postponed without affecting patients' outcome. The European Society for Medical Oncology (ESMO) has endorsed a tiered approach across three different levels of priority (high, medium, low) incorporating information on the value-based prioritisation and clinical cogency of the interventions that can be applied for different disease sites. Patients with gynaecological cancer are at particular risk of COVID-19 complications because of their age and prevalence of comorbidities. The definition of priority level should be based on tumour stage and histology, cancer-related symptoms or complications, aim (curative vs palliative) and magnitude of benefit of the oncological intervention, patients' general condition and preferences. The decision-making process always needs to consider the disease-specific national and international guidelines and the local healthcare system and social resources, and a changing situation in relation to COVID-19 infection. These recommendations aim to provide guidance for the definition of deferrable and undeferrable interventions during the COVID-19 pandemic for ovarian, endometrial and cervical cancers within the context of the ESMO Clinical Practice Guidelines.


Assuntos
Infecções por Coronavirus/terapia , Neoplasias dos Genitais Femininos/terapia , Oncologia/métodos , Pneumonia Viral/terapia , Guias de Prática Clínica como Assunto , Betacoronavirus/fisiologia , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Assistência à Saúde/estatística & dados numéricos , Assistência à Saúde/tendências , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/terapia , Europa (Continente)/epidemiologia , Feminino , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/epidemiologia , Humanos , Oncologia/organização & administração , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/terapia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Sociedades Médicas , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/terapia
10.
Int J Nanomedicine ; 15: 4625-4637, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636622

RESUMO

Purpose: Besides the tumor cells themselves, solid tumors are comprised of numerous cell types including infiltrating immune cells such as tumor-associated macrophages (TAMs). TAMs are vital stromal components of host immune system and play a critical role in the development of cancer. TAMs can be divided into two subtypes: M1 tumor-suppressive macrophage and M2 tumor-supportive macrophage. To better address the observations of TAMs functional performance, we describe an in vitro system that mimics the populations of TAMs infiltrated into the tumor mass by using our disintegrable supramolecular gelatin (DSG) hydrogels, which are physically crosslinked by host-guest complexations. Materials and Methods: The host-guest interaction was adopted between the aromatic groups of gelatin and the photocrosslinkable acrylated ß-cyclodextrins (Ac-ß-CDs) to form the DSG hydrogels. The convenient macrophage/endometrial cancer cells heterospheroid 3D model was set up by DSG hydrogels. RT-PCR and Western blot assays were developed to evaluate the efficiencies of inducers on the macrophages. The ELISA and oxygen saturation assays were performed to measure the secretion of VEGF and consumption of oxygen of tumor and/or macrophages, respectively. To determine the antitumor effects of M2 reprogrammed macrophages in vitro and in vivo, migration assay and tumor xenograft model were used, respectively. Results: The host-guest complexations of DSG hydrogels were controllably broken efficiently by soaking into the solution of competitive guest monomers 1-adamantanamine hydrochloride. The DSG hydrogels help IFN-γ reprogram the M2 to M1 and then decrease the tumor/M2 reprogrammed macrophage cells heterospheroid secretion of VEGF and increase the relative oxygen saturation. Significantly, the co-cultural tumor/M2 reprogrammed group from the disintegrated DSG hydrogels reduced the migration of cancer cells in vitro and the tumor growth in vivo. Conclusion: We obtain a TAMs/tumor microenvironment-responsive 3D model based on the novel DSG hydrogels, and will be of utility in cancer therapy and drug discovery.


Assuntos
Neoplasias do Endométrio/patologia , Gelatina/química , Hidrogéis/química , Macrófagos/citologia , Macrófagos/transplante , Animais , Técnicas de Cultura de Células , Neoplasias do Endométrio/terapia , Matriz Extracelular/patologia , Feminino , Gelatina/farmacocinética , Humanos , Hidrogéis/farmacocinética , Camundongos Endogâmicos BALB C , Esferoides Celulares/citologia , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Eur J Cancer ; 133: 104-111, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32454416

RESUMO

BACKGROUND: Patients with International Federation of Gynaecology and Obstetrics (FIGO) stage III endometrial cancer (EC) have a substantial risk of adverse outcomes. After surgery, adjuvant therapy is recommended with external beam radiotherapy (EBRT), chemotherapy (CT) or both EBRT and CT. Recent trials suggest that EBRT + CT is superior to EBRT or CT alone but also results in more toxicity. We have compared the outcome of different adjuvant treatments in a population-based cohort to identify subgroups that benefit most from EBRT + CT. METHODS: All patients diagnosed with FIGO stage III EC and treated with surgery in 2005-2016 were identified from the Netherlands Cancer Registry. The primary outcome was overall survival (OS); associations with adjuvant treatment were analysed using Cox regression analysis. RESULTS: Among 1241 eligible patients, EBRT + CT was associated with a better OS than CT (hazard ratio [HR] = 1.84, 95% confidence interval [CI] = 1.34-2.52) and EBRT alone (HR = 1.37, 95% CI = 1.05-1.79). In stage IIIC, there was a significant benefit of EBRT + CT compared with CT or EBRT alone. In stage IIIA-B, there was no difference between EBRT + CT or EBRT alone. In endometrioid EC (EEC) and carcinosarcomas, EBRT + CT was associated with a better OS than CT or EBRT alone. For uterine serous cancers, there was no survival benefit of EBRT + CT over CT. In all analysis by stage and histology, any adjuvant treatment was superior to no adjuvant therapy. CONCLUSIONS: In this population-based study, adjuvant EBRT + CT was associated with improved OS compared with CT or EBRT alone in FIGO stage IIIC EC, EEC and carcinosarcoma. This suggests that application of EBRT + CT in stage III should be further stratified according to these subgroups.


Assuntos
Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/terapia , Carcinossarcoma/mortalidade , Carcinossarcoma/terapia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/terapia , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/mortalidade , Braquiterapia/estatística & dados numéricos , Carcinoma Endometrioide/patologia , Carcinossarcoma/patologia , Quimiorradioterapia Adjuvante/métodos , Quimiorradioterapia Adjuvante/mortalidade , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/mortalidade , Quimioterapia Adjuvante/estatística & dados numéricos , Estudos de Coortes , Terapia Combinada/métodos , Terapia Combinada/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histerectomia/mortalidade , Histerectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Países Baixos/epidemiologia , Radioterapia Adjuvante/métodos , Radioterapia Adjuvante/mortalidade , Radioterapia Adjuvante/estatística & dados numéricos , Sistema de Registros , Análise de Sobrevida
12.
Gynecol Oncol ; 157(2): 323-328, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32253046

RESUMO

OBJECTIVES: Given the disparity that exists in enrollment of minorities to oncology clinical trials, the objective of our study was to assess whether race is associated with willingness to participate in gynecologic oncology clinical trials in a rural Southern academic medicine setting. Our secondary aim was to determine whether willingness to participate is impacted by an educational intervention. METHODS: A single institution prospective survey study was performed at an academic medical center. Women presenting to the gynecologic oncology clinic with a current or prior diagnosis of gynecologic malignancy were approached to participate. The validated Attitudes to Randomized Trials Questionnaire (ARTQ) assessed willingness to participate in clinical trials. Relevant demographic and clinical data were abstracted. Characteristics were compared between those willing and unwilling to participate in clinical trials with a chi-square test for categorical variables and Wilcoxon rank sum tests for continuous data. RESULTS: We enrolled 156 participants (50% White, 50% non-White) from May 2017 to January 2018. The minority group included 35% non-Hispanic Black, 9% Hispanic, 4% Asian, and 2% other. Median age was 63 years with endometrial cancer being the most common diagnosis (48%). On initial screen, only 35% were willing to participate in a clinical trial. Willingness to participate did not differ between race, age, marital status, education level, cancer type, stage, or mode of treatment. Rates improved to 82% after being provided additional educational information. Following education, White women and those with more education were significantly more willing to participate in clinical trials than their minority and less educated counterparts. CONCLUSIONS: Willingness to participate improved among all sub-categories following an educational intervention. The increase in willingness was less robust among racial and ethnic minorities, suggesting that different tools are needed for recruitment of minorities to gynecologic oncology clinical trials.


Assuntos
Neoplasias do Endométrio/etnologia , Neoplasias do Endométrio/terapia , Grupos Étnicos/psicologia , Grupos Minoritários/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto/psicologia , Grupo com Ancestrais do Continente Africano/psicologia , Idoso , Americanos Asiáticos/psicologia , Neoplasias do Endométrio/psicologia , Grupo com Ancestrais do Continente Europeu/psicologia , Feminino , Hispano-Americanos/psicologia , Humanos , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/métodos , Estudos Prospectivos , Inquéritos e Questionários , Estados Unidos
13.
Hum Cell ; 33(3): 790-800, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32304027

RESUMO

Anterior gradient 2 (AGR2) was proved to modulate cancer progression. However, the role of AGR2 on endometrial cancer was not established. Here, we investigated the effects of AGR2 expression on endometrial cancer and explored the regulation mechanism. In the study, we found that AGR2 was overexpressed in tumor tissues of 30 endometrial cancer patients. A high level of AGR2 promoted endometrial cancer cells proliferation, migration and invasion. AGR2 induced the expression of lactate dehydrogenase A (LDHA), phosphoglycerate kinase 1 (PGK1), kallikrein 2 (HK2), and enolase 1-α (ENO1), glucose uptake and lactate production. AGR2 could bind to MUC1 and induce MUC1 and hypoxia-inducible factor 1α (HIF-1α). The inhibition effects of AGR2 knockdown on cells proliferation, migration and invasion ability were abolished by the overexpression of MUC1. Besides, the overexpression of MUC1 also reversed the inhibition effects of AGR2 knockdown on the expression of LDHA, HK2, PGK1 and ENO1, glucose uptake and lactate production. AGR2 knockdown inhibited tumor growth, the levels of Ki-67, MUC1, HIF-1α and glycolysis. In conclusion, AGR2 was overexpressed in endometrial cancer and AGR2-induced glucose metabolism facilitated the progression of endometrial carcinoma via the MUC1/HIF-1α pathway. AGR2 may be an effective therapeutic target for endometrial carcinoma.


Assuntos
Carcinoma/genética , Carcinoma/patologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Glucose/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Mucina-1/genética , Mucina-1/metabolismo , Mucoproteínas/fisiologia , Proteínas Oncogênicas/fisiologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma/metabolismo , Carcinoma/terapia , Movimento Celular/genética , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Progressão da Doença , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/terapia , Feminino , Expressão Gênica , Hexoquinase/genética , Hexoquinase/metabolismo , Humanos , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Terapia de Alvo Molecular , Mucoproteínas/genética , Mucoproteínas/metabolismo , Invasividade Neoplásica/genética , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Fosfoglicerato Quinase/genética , Fosfoglicerato Quinase/metabolismo , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
14.
J Ovarian Res ; 13(1): 37, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293505

RESUMO

BACKGROUND: Although lncRNA CTBP1-AS2 has been functionally analyzed only in cardiomyocyte hypertrophy and diabetes, analysis of TCGA dataset revealed its downregulation in endometrial carcinoma (EC), indicating its involvement in EC. RESULTS: In this study we found that CTBP1-AS2 was downregulated in EC and correlated with poor survival. MiR-216a might form base pairs with CTBP1-AS2 based on RNA-RNA interaction, which was confirmed by luciferase activity assay. Interestingly, upregulation of PTEN was observed after CTBP1-AS2 overexpression. Transwell assay showed that CTBP1-AS2 and PTEN overexpression led to decreased cancer cell invasion and migration and reduced enhancing effects of miR-216a on cell invasion and migration. It was known that miR-216a targeted PTEN. CONCLUSION: Therefore, CTBP1-AS2 may sponge miR-216a to upregulate PTEN, thereby suppressing endometrial cancer cell invasion and migration.


Assuntos
Neoplasias do Endométrio/genética , MicroRNAs , PTEN Fosfo-Hidrolase/genética , RNA Longo não Codificante , Linhagem Celular Tumoral , Movimento Celular , Regulação para Baixo , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Invasividade Neoplásica , PTEN Fosfo-Hidrolase/metabolismo , Regulação para Cima
15.
Nat Rev Clin Oncol ; 17(6): 349-359, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32152484

RESUMO

Folate receptor α (FRα) came into focus as an anticancer target many decades after the successful development of drugs targeting intracellular folate metabolism, such as methotrexate and pemetrexed. Binding to FRα is one of several methods by which folate is taken up by cells; however, this receptor is an attractive anticancer drug target owing to the overexpression of FRα in a range of solid tumours, including ovarian, lung and breast cancers. Furthermore, using FRα to better localize effective anticancer therapies to their target tumours using platforms such as antibody-drug conjugates, small-molecule drug conjugates, radioimmunoconjugates and, more recently, chimeric antigen receptor T cells could further improve the outcomes of patients with FRα-overexpressing cancers. FRα can also be harnessed for predictive biomarker research. Moreover, imaging FRα radiologically or in real time during surgery can lead to improved functional imaging and surgical outcomes, respectively. In this Review, we describe the current status of research into FRα in cancer, including data from several late-phase clinical trials involving FRα-targeted therapies, and the use of new technologies to develop FRα-targeted agents with improved therapeutic indices.


Assuntos
Antineoplásicos/uso terapêutico , Receptor 1 de Folato/metabolismo , Imunoconjugados/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imagem Molecular , Neoplasias/metabolismo , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Epitelial do Ovário/diagnóstico por imagem , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/terapia , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/terapia , Feminino , Corantes Fluorescentes , Ácido Fólico , Antagonistas do Ácido Fólico/uso terapêutico , Humanos , Imunoterapia Adotiva , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Maitansina/análogos & derivados , Maitansina/uso terapêutico , Mesotelioma/diagnóstico por imagem , Mesotelioma/metabolismo , Mesotelioma/terapia , Terapia de Alvo Molecular , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Imagem Óptica , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/terapia , Cintilografia , Nanomedicina Teranóstica , Moduladores de Tubulina/uso terapêutico
16.
Anticancer Res ; 40(3): 1669-1676, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132073

RESUMO

AIM: To study whether mismatch repair (MMR) status is related to the expression of programmed cell death-ligand 1 (PD-L1) and CD8 counts in a series of grade 3 endometrial carcinomas. MATERIALS AND METHODS: The expression of MMR protein PD-L1 and CD8+ cell count were evaluated by immunohistochemistry and related to several clinicopathological parameters. RESULTS: Among 105 endometrial carcinomas, 40% were of endometrioid and 60% of non-endometrioid histology. MMR deficiency was observed in 28.6% of cases and was related to endometrioid histology (p<0.001), positive PD-L1 expression (p=0.047) and high CD8+ cell count (p=0.022). When examined by histotype, endometrioid MMR-deficient tumors were related only to PD-L1 expression (p=0.032) but not to high CD8+ cell count (p=0.231), whereas non-endometrioid MMR-deficient carcinomas were not related to either of these markers. MMR deficiency was associated with PD-L1+/CD8high status (p=0.006), whilst MMR proficiency was associated with PD-L1-/CD8low status. In MMR-proficient tumors, high CD8+ cell infiltration alone and combined with PD-L1- status was associated with better progression-free survival (p=0.013 and p=0.04, respectively). CONCLUSION: MMR-deficient high-grade endometrioid tumors might be more likely to benefit from immunotherapy compared to other grade 3 endometrial carcinomas.


Assuntos
Biomarcadores Tumorais/metabolismo , Reparo de Erro de Pareamento de DNA/imunologia , Neoplasias do Endométrio/terapia , Imunoterapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade
17.
Am J Obstet Gynecol ; 223(3): 398.e1-398.e18, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32142825

RESUMO

BACKGROUND: Differences in receipt of guideline-concordant treatment might underlie well-established racial disparities in endometrial cancer mortality. OBJECTIVE: Using the National Cancer Database, we assessed the hypothesis that among women with endometrioid endometrial cancer, racial/ethnic minority women would have lower odds of receiving guideline-concordant treatment than white women. In addition, we hypothesized that lack of guideline-concordant treatment was linked with worse survival. STUDY DESIGN: We defined receipt of guideline-concordant treatment using the National Comprehensive Cancer Network guidelines. Multivariable logistic regression models were used to compute odds ratios and 95% confidence intervals for associations between race and guideline-concordant treatment. We used multivariable Cox proportional hazards regression models to estimate hazards ratios and 95% confidence intervals for relationships between guideline-concordant treatment and overall survival in the overall study population and stratified by race/ethnicity. RESULTS: This analysis was restricted to the 89,319 women diagnosed with an invasive, endometrioid endometrial cancer between 2004 and 2014. Overall, 74.7% of the cohort received guideline-concordant treatment (n = 66,699). Analyses stratified by race showed that 75.3% of non-Hispanic white (n = 57,442), 70.1% of non-Hispanic black (n = 4334), 71.0% of Hispanic (n = 3263), and 72.5% of Asian/Pacific Islander patients (n = 1660) received treatment in concordance with guidelines. In multivariable-adjusted models, non-Hispanic black (odds ratio, 0.92, 95% confidence interval, 0.86-0.98) and Hispanic women (odds ratio, 0.90, 95% confidence internal, 0.83-0.97) had lower odds of receiving guideline-concordant treatment compared with non-Hispanic white women, while Asian/Pacific Islander women had a higher odds of receiving guideline-concordant treatment (odds ratio, 1.11, 95% confidence interval, 1.00-1.23). Lack of guideline-concordant treatment was associated with lower overall survival in the overall study population (hazard ratio, 1.12, 95% confidence interval, 1.08-1.15) but was not significantly associated with overall survival among non-Hispanic black (hazard ratio, 1.09, 95% confidence interval, 0.98-1.21), Hispanic (hazard ratio, 0.92, 95% confidence interval=0.78-1.09), or Asian/Pacific Islander (hazard ratio, 0.90, 95% confidence interval, 0.70-1.16) women. CONCLUSION: Non-Hispanic black and Hispanic women were less likely than non-Hispanic white women to receive guideline-concordant treatment, while Asian/Pacific Islander women more commonly received treatment in line with guidelines. Furthermore, in the overall study population, overall survival was worse among those not receiving guideline-concordant treatment, although low power may have had an impact on the race-stratified models. Future studies should evaluate reasons underlying disparate endometrial cancer treatment.


Assuntos
Carcinoma Endometrioide/terapia , Neoplasias do Endométrio/terapia , Fidelidade a Diretrizes/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Adulto , Afro-Americanos , Idoso , Carcinoma Endometrioide/etnologia , Carcinoma Endometrioide/mortalidade , Neoplasias do Endométrio/etnologia , Neoplasias do Endométrio/mortalidade , Grupos Étnicos , Grupo com Ancestrais do Continente Europeu , Feminino , Hispano-Americanos , Humanos , Pessoa de Meia-Idade , Grupos Minoritários , Estadiamento de Neoplasias , Grupo com Ancestrais Oceânicos , Razão de Chances , Modelos de Riscos Proporcionais , Taxa de Sobrevida
18.
Am J Surg Pathol ; 44(5): 641-648, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32205482

RESUMO

Endometrial carcinoma (EC), as described by Bokhman, has historically been classified as Type I (low-grade, hormone-dependant, young patients, good prognosis) or Type II (high-grade, hormone-independent, older patients, poor prognosis). This classification is no longer pragmatic, however, as EC is a much more heterogeneous disease. Four molecular subtypes of EC were identified by The Cancer Genome Atlas (TCGA), and subsequent studies have demonstrated its utility in predicting prognosis. While endometrial serous carcinoma (ESC), the prototypical Type II EC, largely occurs in older women, younger women with ESC were not accounted for in the Bokhman model and were underrepresented in the TCGA study. We hypothesized that a subset of ESCs in young patients do not represent bona fide serous carcinomas but rather high-grade endometrioid carcinomas mimicking a serous phenotype. We identified ESCs and mixed endometrioid/serous carcinomas in women <60 years (n=37), and analyzed their clinical, morphologic, immunohistochemical, and molecular characteristics. Sixteen percent showed mismatch repair deficiency (MMR-D) and 11% were diagnosed with Lynch syndrome. Additionally, 16% of cases tested harbored a hotspot POLE exonuclease domain mutation (POLE-EDM). Morphologically, 47% of tumors showed confirmatory endometrioid features, including atypical hyperplasia, a low-grade endometrioid carcinoma component, or squamous differentiation. Clinically, the overall survival in patients with MMR-D and POLE-EDM was significantly better than that of patients without these features (P=0.0329). In conclusion, ESCs in young patients comprise a heterogeneous group of tumors, demonstrating diverse clinical, immunohistochemical, morphologic, and molecular features which have implications for prognosis and adjuvant therapy.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA , DNA Polimerase II/genética , Enzimas Reparadoras do DNA/deficiência , Neoplasias do Endométrio/genética , Mutação , Neoplasias Complexas Mistas/genética , Neoplasias Císticas, Mucinosas e Serosas/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Adulto , Fatores Etários , Neoplasias Colorretais Hereditárias sem Polipose/enzimologia , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Neoplasias Colorretais Hereditárias sem Polipose/terapia , Neoplasias do Endométrio/enzimologia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Complexas Mistas/enzimologia , Neoplasias Complexas Mistas/patologia , Neoplasias Complexas Mistas/terapia , Neoplasias Císticas, Mucinosas e Serosas/enzimologia , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Císticas, Mucinosas e Serosas/terapia , Fenótipo , Fatores de Risco , Fatores de Tempo
19.
Ginekol Pol ; 91(1): 6-12, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32039461

RESUMO

OBJECTIVES: Since 1990s the number of patients diagnosed with endometrial cancer (EC) has doubled. The standard treatment method for treating early endometrial cancer is surgery. Some patients require a subsequent adjuvant therapy. In early endometrial cancers its application is limited to the populations with a high risk of recurrence. The aim of this study was to assess the effectiveness of early endometrial cancer treatment based on an analysis of 5-year follow up of EC patients. MATERIAL AND METHODS: The analysis consisted in a retrospective non-randomized interventional study of patients treated for early endometrial cancer (FIGO stage IA, IB, II). Its end point was either local (small pelvis) or distant recurrence of the disease. Intervention involved an adjuvant treatment applied in selected patients according to the current guidelines for EC treatment. There was no randomization for adjuvant and non-adjuvant EC treatment. The study included a total of 419 patients treated for EC from 2010 to 2012. RESULTS: The analysis revealed that 108 patients (25.8%) were diagnosed with the recurrent disease. Out of 112 patients treated for stage IA endometrial cancer 32 (28.6%) experienced recurrence. Out of 216 patients at FIGO Stage IB, recurrence was diagnosed in 38 (17.6%). In the group of 91 patients treated for FIGO stage II, EC the recurrence was diagnosed in 38 (41.2%) cases. CONCLUSIONS: Early EC treatment results were unsatisfactory and should be improved. The best outcomes were achieved in patients with IA stage of EC who received a radiation therapy.


Assuntos
Adenocarcinoma de Células Claras/terapia , Carcinoma Endometrioide/terapia , Quimioterapia Adjuvante/métodos , Terapia Combinada/métodos , Neoplasias do Endométrio/terapia , Radioterapia Adjuvante/métodos , Prevenção Secundária/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
20.
Gynecol Oncol ; 157(2): 312-322, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32014330

RESUMO

For over forty years, the Gynecologic Oncology Group drove progress in treating endometrial cancer. The first decades of investigation began with a meticulous prospective, surgicopathologic staging study that was the platform for development of all subsequent trials. The resultant statistical model of low risk, intermediate risk, and high-risk groups of patients led to trials where therapeutic modalities were best targeted at disease spread. A clear role for chemotherapy was established. It was realized that greater advances might be achieved with the advent of newer anti-neoplastic agents and these agents were subjected to extensive phase II testing. These agents later were integrated into comparison trials for advanced endometrial cancer. Multimodality therapy continues to show promise. Hormonal therapy was thoroughly investigated and led to combination hormonal therapy trials. Newer agents, including biologics are under active study, as well as the potential contribution of modern imaging techniques. Finally, GOG0210 established a repository of clinical specimens with detailed clinical and epidemiologic data from patients with surgically staged endometrial carcinoma. This should provide for a much greater understanding of molecular characteristics associated with risk of endometrial cancer recurrence, clinical and histological characteristics, and epidemiologic factors.


Assuntos
Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Animais , Feminino , Humanos , Estadiamento de Neoplasias , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
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