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1.
Tumour Biol ; 42(8): 1010428320951057, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32829673

RESUMO

The exchange of metabolites between mitochondria and cytosol occurs through pores formed by voltage-dependent anion channel proteins. Voltage-dependent anion channels appear to be master regulators of mitochondrial bioenergetics and the intracellular flow of energy. Deregulation of voltage-dependent anion channels expression is thought to be related to mitochondrial dysfunction in cancer. The aim of this study was to investigate the mRNA and protein expression levels of VDAC1, VDAC2, and VDAC3 in relation to clinicopathological characteristics of endometrial cancer as well as the prognostic significance of voltage-dependent anion channels expression for overall survival. VDAC1 and VDAC3 expressions were significantly higher in cancer compared to normal tissues. Kaplan-Meier analysis indicated that high expression of all VDAC genes or high VDAC2 protein level predicted poor overall survival. Multivariate analysis identified the VDAC1 and VDAC2 mRNA levels as well as VDAC2 protein level as independent prognostic factors. Our results suggest that increased expression of voltage-dependent anion channels correlates with tumor progression and may serve as a potential prognostic biomarker in endometrial cancer.


Assuntos
Neoplasias do Endométrio/patologia , Mitocôndrias/patologia , Proteínas de Transporte da Membrana Mitocondrial/genética , Canal de Ânion 1 Dependente de Voltagem/genética , Canal de Ânion 2 Dependente de Voltagem/genética , Canais de Ânion Dependentes de Voltagem/genética , Sequência de Aminoácidos , Biomarcadores Tumorais/genética , Citoplasma/metabolismo , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/biossíntese , Prognóstico , RNA Mensageiro/genética , Canal de Ânion 1 Dependente de Voltagem/biossíntese , Canal de Ânion 2 Dependente de Voltagem/biossíntese , Canais de Ânion Dependentes de Voltagem/biossíntese
2.
J Cancer Res Clin Oncol ; 146(7): 1725-1735, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32394054

RESUMO

OBJECTIVE: The plasminogen activator system (PAS) and vascular endothelial growth factor (VEGF) are important in the carcinogenesis and play a key role in cancer invasion and mediating metastasis of carcinomas. The aim of the study was to evaluate the correlation of serum levels of VEGF and components of the PAS with clinicopathological risk factors and outcome in patients with endometrial cancer (EC). METHODS: Preoperative blood was collected from 173 patients treated for EC between 1999 and 2009. Serum concentrations of VEGF, urokinase plasminogen activator (uPA) tissue plasminogen activator (tPA), plasminogen activator inhibitor type-1 (PAI-1) and -2 (PAI-2) were assessed by enzyme-linked immunosorbent assays (ELISA). RESULTS: Serum levels of VEGF and components of the PAS were significantly associated with stage of the disease, tumor histology, tumor grade, myometrial invasion (MI), presence of lymphovascular space invasion (LVSI) and lymph node metastases (LNM). Preoperative serum levels of PAI-1 and -2 and tPA were higher in patients who experienced a recurrence than in patients who remained disease free (p < 0.01). PAI-1 and -2 and tPA were significantly independent prognostic factors for DFS with a HR of 3.85 (95% CI 1.84-8.07), 3.90 (95% CI 1.75-8.66) and 2.53 (95% CI 1.16-5.55), respectively. PAI-1 and tPA turned out to be independent prognostic factors for OS, with a HR of 2.09 (95% CI 1.08-4.05) and 2.16 (95% CI 1.06-4.44), respectively. CONCLUSION: Serum levels of VEGF and components of the PAS at primary diagnosis were associated with well-known clinicopathological risk factors such as; FIGO stage, tumor histology, tumor grade, MI, LVSI and LNM. High concentrations of PAI-1 and-2 and tPA are independent factors for poor prognosis in patients with endometrial cancer.


Assuntos
Neoplasias do Endométrio/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Idoso , Biomarcadores Tumorais , Transformação Celular Neoplásica , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/etiologia , Neoplasias do Endométrio/mortalidade , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Modelos Moleculares , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Ativador de Plasminogênio Tecidual/sangue , Ativador de Plasminogênio Tecidual/metabolismo , Fator A de Crescimento do Endotélio Vascular/sangue
3.
Arch Gynecol Obstet ; 302(1): 249-263, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32468162

RESUMO

BACKGROUND: Lymph node metastasis is a principal prognostic factor for the treatment of endometrial cancer. Added value of para-aortic lymphadenectomy to only pelvic lymphadenectomy for intermediate/high-risk endometrial cancer patients remains controversial. OBJECTIVE: A systematic review and meta-analysis was performed to assess the impact of combined pelvic and para-aortic lymph node dissection (PPALND) compared to only pelvic lymph node dissection (PLND) on survival outcomes of intermediate and/or high-risk patients. STUDY DESIGN: The systematic review and meta-analysis adhered to the PRISMA guidelines for meta-analyses of interventional studies. Pubmed, Scopus, EMBASE and Cochrane were searched up to April 20, 2018. Included studies were those comparing high-risk endometrial cancer patients that had performed pelvic and para-aortic lymph node dissection (PPALND) vs. only pelvic lymph node dissection (PLND) apart from standard procedure (total hysterectomy with bilateral salpingo-oophorectomy, TAHBSO). Primary outcomes of the study were overall survival and disease-free survival rates. Methodological quality of the included studies was assessed using the ROBINS-I tool. Overall quality of the evidence for the primary and secondary outcomes was evaluated as per GRADE guideline using the GRADE pro GD tool. RESULTS: There were 13 studies identified with 7349 patients included. All studies were retrospective observational as no RCTs or prospective studies adhering to inclusion criteria were retrieved. Combined pelvic and para-aortic lymphadenectomy was associated with 46% decreased risk for death (HR 0.54, 95% CI 0.35-0.83, I2 = 62.1%) and 49% decreased risk for recurrence (HR 0.51, 95% CI 0.28-0.93). It was also associated with increased 5-year OS rate (RR 1.13, 95% CI 1.04-0.24, I2 = 57.3%) and increased 5-year DFS rate (RR 1.23, 95% CI 1.14-1.31, I2 = 85.5) compared with only pelvic lymphadenectomy. CONCLUSION: Combined pelvic and para-aortic lymphadenectomy is associated with improved survival outcomes compared with only pelvic lymphadenectomy in women with intermediate/high-risk endometrial cancers. Further prospective studies should be performed.


Assuntos
Neoplasias do Endométrio/cirurgia , Excisão de Linfonodo/métodos , Linfonodos/patologia , Metástase Linfática/patologia , Adulto , Idoso , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
4.
Aging (Albany NY) ; 12(8): 6518-6535, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: covidwho-140657

RESUMO

Angiotensin-converting enzyme 2 (ACE2) is a member of the renin-angiotension system, however, the correlation between ACE2 and prognosis in UCEC (Uterine Corpus Endometrial Carcinoma) and KIRP (Kidney Renal Papillary Cell Carcinoma) is not clear. We analyzed the expression levels of ACE2 in the Oncomine and TIMER databases, the correlation between ACE2 and overall survival in the PrognoScan, GEPIA and Kaplan-Meier plotter databases. The correlation between ACE2 and immune infiltration level and the type markers of immune cells was investigated in TIMER database. A prognosis analysis based on the expression levels of ACE2 was further performed in related immune cells subgroup. The ACE2 promoter methylation profile was tested in the UALCAN database. In addition, we used GSE30589 and GSE52920 databases to elucidate the changes of ACE2 expression in vivo and in vitro after SARS-CoV infection. ACE2 was elevated in UCEC and KIRP, and high ACE2 had a favorable prognosis. The expression of ACE2 was positively correlated with the level of immune infiltration of macrophage in KIRP, B cell, CD4+T cell, neutrophil and dendritic cell immune infiltration levels in UCEC. ACE2 was significantly positively correlated with the type markers of B cells and neutrophils, macrophages in UCEC, while ACE2 in KIRP was positively correlated with the type markers of macrophages. High ACE2 expression level had a favorable prognosis in different enriched immune cells subgroups in UCEC and KIRP. And the promoter methylation levels of ACE2 in UCEC and KIRP were significantly reduced. What's more, we found that the expression of ACE2 decreased in vivo and in vitro after SARS-CoV infection. In conclusion, ACE2 expression increased significantly in UCEC and KIRP, elevated ACE2 was positively correlated with immune infiltration and prognosis. Moreover, tumor tissues may be more susceptible to SARS-CoV-2 infection in COVID-19 patients with UCEC and KIRP, which may worsen the prognosis.


Assuntos
Betacoronavirus , Carcinoma de Células Renais , Infecções por Coronavirus , Neoplasias do Endométrio , Imunidade Celular , Neoplasias Renais , Pandemias , Peptidil Dipeptidase A/biossíntese , Pneumonia Viral , Biomarcadores Tumorais , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Prognóstico
5.
Aging (Albany NY) ; 12(8): 6518-6535, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32339157

RESUMO

Angiotensin-converting enzyme 2 (ACE2) is a member of the renin-angiotension system, however, the correlation between ACE2 and prognosis in UCEC (Uterine Corpus Endometrial Carcinoma) and KIRP (Kidney Renal Papillary Cell Carcinoma) is not clear. We analyzed the expression levels of ACE2 in the Oncomine and TIMER databases, the correlation between ACE2 and overall survival in the PrognoScan, GEPIA and Kaplan-Meier plotter databases. The correlation between ACE2 and immune infiltration level and the type markers of immune cells was investigated in TIMER database. A prognosis analysis based on the expression levels of ACE2 was further performed in related immune cells subgroup. The ACE2 promoter methylation profile was tested in the UALCAN database. In addition, we used GSE30589 and GSE52920 databases to elucidate the changes of ACE2 expression in vivo and in vitro after SARS-CoV infection. ACE2 was elevated in UCEC and KIRP, and high ACE2 had a favorable prognosis. The expression of ACE2 was positively correlated with the level of immune infiltration of macrophage in KIRP, B cell, CD4+T cell, neutrophil and dendritic cell immune infiltration levels in UCEC. ACE2 was significantly positively correlated with the type markers of B cells and neutrophils, macrophages in UCEC, while ACE2 in KIRP was positively correlated with the type markers of macrophages. High ACE2 expression level had a favorable prognosis in different enriched immune cells subgroups in UCEC and KIRP. And the promoter methylation levels of ACE2 in UCEC and KIRP were significantly reduced. What's more, we found that the expression of ACE2 decreased in vivo and in vitro after SARS-CoV infection. In conclusion, ACE2 expression increased significantly in UCEC and KIRP, elevated ACE2 was positively correlated with immune infiltration and prognosis. Moreover, tumor tissues may be more susceptible to SARS-CoV-2 infection in COVID-19 patients with UCEC and KIRP, which may worsen the prognosis.


Assuntos
Betacoronavirus , Carcinoma de Células Renais , Infecções por Coronavirus , Neoplasias do Endométrio , Imunidade Celular , Neoplasias Renais , Pandemias , Peptidil Dipeptidase A/biossíntese , Pneumonia Viral , Biomarcadores Tumorais , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Prognóstico
6.
Orv Hetil ; 161(11): 425-433, 2020 Mar.
Artigo em Húngaro | MEDLINE | ID: mdl-32148096

RESUMO

Introduction: Endometrial cancer is the most common invasive gynecologic malignancy in developed countries. The best survival rates are expected after surgical removal, thus the aim of a complex treatment is to achieve resecability in locally and locoregionally advanced disease. Aim: The primary purpose of this study was to evaluate if the neoadjuvant systemic treatment leads to better overall survival compared to irradiation solely. Method: From January 2015 to December 2018, we enrolled 28 patients diagnosed with irresecable, locally and locoregionally advanced high-risk endometrial carcinoma. Patients were treated by neoadjuvant paclitaxel-carboplatin, then radical hysterectomy, bilateral oophorectomy and lymphadenectomy were performed. Results: After administration of 6 cycles of carboplatin-paclitaxel, the control MR test showed tumor shrinkage in all patients. Complete resection was achieved in the case of every patient. Tumor residuum in lymph nodes was verified in 4 cases by pathological evaluation. The 2-year survival and the 2-year progression-free survival rates were 65,1% and 66,1%, respectively. The median overall survival was 16,5 months. Conclusion: Neoadjuvant treatment can be an effective approach in providing the conditions for complete tumor resection, which may result in survival advantage. Despite multimodal treatment, prognosis is poor. Orv Hetil. 2020; 161(11): 425-433.


Assuntos
Carboplatina/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/cirurgia , Terapia Neoadjuvante , Paclitaxel/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino/uso terapêutico , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Excisão de Linfonodo , Estadiamento de Neoplasias , Ovariectomia , Taxa de Sobrevida , Resultado do Tratamento
7.
Am J Clin Oncol ; 43(6): 411-417, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32205571

RESUMO

BACKGROUND: Metabolic syndrome has previously been linked to increased risk of endometrial cancer. This study examines the association between metabolic syndrome and cancer-specific survival (CSS) in early stage and locoregionally advanced endometrial cancer. METHODS: The SEER-Medicare linked database was used to identify a cohort of patients with endometrial cancer between 1992 and 2011 who underwent hysterectomy. Patients with incomplete stage or grade information were excluded. Patients were stratified into early stage (stage I to II) or locoregionally advanced (stage III to IVa) disease. Metabolic syndrome status was determined through Medicare claims 1 year before diagnosis. The relationship between metabolic syndrome and CSS was evaluated using univariable and multivariable Cox proportional hazards regression analyses. RESULTS: A total of 10,090 patients with endometrial cancer were identified. The mean age was 75 and the majority (91.5%) were white. At diagnosis, 86.6% of patients were early stage and 13.4% were locoregionally advanced. Sixteen percent of patients had metabolic syndrome. On stage stratified multivariable analysis, race, income quartile, year of diagnosis, histopathology, and adjuvant treatment were associated with CSS in early stage disease. Presence of metabolic syndrome was associated with worse CSS in early stage disease (hazard ratio=1.28, 95% confidence interval: 1.09-1.53); this difference did not exist for locoregionally advanced disease (hazard ratio=1.18, 95% confidence interval: 0.93-1.49). CONCLUSIONS: In elderly early stage endometrial cancer patients, metabolic syndrome is associated with worse CSS. Control of metabolic syndrome through lifestyle and pharmacologic therapies may improve cancer prognosis in this population.


Assuntos
Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/mortalidade , Síndrome Metabólica/complicações , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Bases de Dados Factuais , Neoplasias do Endométrio/patologia , Feminino , Humanos , Medicare , Estadiamento de Neoplasias , Programa de SEER , Taxa de Sobrevida , Estados Unidos
8.
Anticancer Res ; 40(3): 1563-1570, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132058

RESUMO

BACKGROUND/AIM: This study aimed to determine whether a pelvic and para-aortic lymphadenectomy (PPAL) improves survival compared with a pelvic lymphadenectomy (PL) in patients with endometrial cancer. PATIENTS AND METHODS: Data from all women operated for endometrial cancer between 1998 and 2013 were extracted from the Surveillance, Epidemiology and End Results database. Women treated with PL were matched with those treated with PPAL according to age and risk of recurrence. The primary endpoint was disease-specific survival (DSS). RESULTS: A total of 1015 patients who underwent PL were matched with 1015 patients who underwent PPAL. The 3-year DSS probabilities for patients at intermediate- and high-risk (IHR) of recurrence were similar in the PPAL group and the PL group. Multivariate analysis of prognostic factors indicated that in patients with an IHR of recurrence, PPAL did not reduce the risk of death compared with PL. CONCLUSION: For patients with an IHR of recurrence, the extent of lymphadenectomy does not impact DSS.


Assuntos
Neoplasias do Endométrio/cirurgia , Excisão de Linfonodo/métodos , Estudos de Coortes , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Taxa de Sobrevida
9.
Orv Hetil ; 161(10): 382-388, 2020 Mar.
Artigo em Húngaro | MEDLINE | ID: mdl-32115990

RESUMO

Introduction: Recently published unfavourable results of endoscopic radical surgery for early-stage cervical cancer compared to open surgery raises the need for auditing treatment results of endoscopic staging surgery for endometrial cancer. Aim: Comparison of progression-free and overall survival (PFS and OS) between endometrial cancer patients treated with laparoscopic (LSC) and open surgical techniques. Method: Retrospective analysis was performed to compare clinicopathological and survival data of endometrial cancer patients who had either laparoscopic or open staging surgery between 2013 and 2019 at the Gynaecological Oncology Unit of the University of Debrecen, Hungary. Distribution of the most relevant prognostic factors were compared with χ2 and t-tests. Frequencies of progressive disease and disease-specific deaths were compared in the Cox-model, while progression-free and overall survival curves were compared with the Kaplan-Meier method. Results: The frequency of endometrioid, serous papillary, mixed Müllerian, adenosquamous and other histological types in the laparoscopic and open groups were similar (p = 0.3356). The frequency of grade 1, 2 and 3 tumours in the endoscopic and open groups showed significant differences (p = 0.0036). Pathological stage-distribution (IA, IB, II, IIIA, IIIB, IIIC1, IIIC2) of endoscopic cases and open cases was also statistically different (p = 0.0048). The mean number of removed lymph-nodes was higher in the open surgery group (14.3 vs. 9,3, p<0.0001). The frequency of recurrence did not show significant difference between the two groups, in contrast to the frequency of disease-specific deaths (2/120 vs. 29/345, p = 0.01; 2/120 vs. 17/345, p = 0.12). In the Cox-model, progression-free survival and overall survival showed a hazard ratio favouring laparoscopic surgery, however, the range of 95% confidence intervals showed no statistical significance (PFS LSC vs. open: HR = 0.36, 95% CI = 0.084-1.538; OS LSC vs. open: HR = 0.603, 95% CI = 0.135-2.693). Conclusion: Progression-free and overall survival of endoscopically staged endometrial cancer is not worse than those of patients staged with open surgery. Orv Hetil. 2020; 161(10): 382-388.


Assuntos
Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/cirurgia , Histerectomia , Laparoscopia/métodos , Intervalo Livre de Doença , Neoplasias do Endométrio/patologia , Feminino , Humanos , Hungria/epidemiologia , Excisão de Linfonodo , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
10.
Future Oncol ; 16(8): 307-316, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32039638

RESUMO

Aim: To reveal the prognostic significance of serum albumin (ALB) concentration in endometrial cancer (EC) patients in China. Patients & methods: 345 EC patients were enrolled in a single center, and the preoperative serum ALB concentration were measured. Kaplan-Meier curve analysis and Cox proportional hazards regression model were performed to evaluate the associations between ALB concentration and overall survival (OS) of EC patients. Results: The EC patients with lower preoperative serum ALB concentration exhibited a significantly poorer OS (p < 0.05). Univariate analysis and multivariate analysis indicated that serum ALB concentration was an independent prognostic factor of unfavorable OS for EC patients. Conclusion: Our results showing that ALB concentration may serve as an independent prognostic factor for EC patients.


Assuntos
Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/mortalidade , Hipoalbuminemia/complicações , Período Pré-Operatório , Adulto , Idoso , Biomarcadores , China , Terapia Combinada , Gerenciamento Clínico , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Resultado do Tratamento
12.
Dis Markers ; 2020: 1805764, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32076456

RESUMO

Background: The association between tumour-infiltrating immune cells and the prognosis of endometrial cancer (EC) is controversial due to the smaller sample sizes and limited statistical power of the extant studies. We carried out a meta-analysis of the relationship between tumour-infiltrating immune cells and EC survival outcomes. Methods: A literature search in multiple databases was carried out up to December 2019. Pooled hazard ratio (HRs) and 95% confidence intervals (CIs) were calculated by the Z-test to assess the association between infiltrating immune cells and overall survival (OS), progression-free survival (PFS), relapse-free survival (RFS), disease-specific survival (DSS), and disease-free survival (DFS). A subgroup analysis was performed based on the localisation of immune cells in tumour parenchyma or stroma, immune markers, and the International Federation of Gynecology and Obstetrics stage. Heterogeneity and publication bias between studies were evaluated by Cochran's Q-test and Egger regression test, respectively. Results: Seventeen studies were included in the analysis. The pooled HR of OS, PFS, DSS, and DFS indicated that a high CD8+ T cell density was associated with a favorable prognosis in EC patients. A significant relationship was found between a high density of CD45RO+ T cells and a favorable OS in EC patients, but the FoxP3+ T cell density was not associated with either OS or RFS. A high TAM density was associated with a worse PFS. However, a sensitivity analysis indicated that the findings of PFS and DSS in CD8+ T cell and PFS in TAM were not robust results. Conclusion: This is the first meta-analysis of the relationship between tumour-infiltrating immune cells and the prognosis of EC. High CD8+ and CD45RO+ T cell densities in tumours were associated with favorable outcomes in EC patients.


Assuntos
Biomarcadores Tumorais/imunologia , Neoplasias do Endométrio/mortalidade , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Neoplasias do Endométrio/imunologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Antígenos Comuns de Leucócito/metabolismo , Prognóstico , Análise de Sobrevida
13.
Support Care Cancer ; 28(10): 4901-4909, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32008090

RESUMO

PURPOSE: Health-related quality of life (HRQOL) is an important prognostic factor in cancer patients. To date, no other studies have assessed the association between HRQOL measured before diagnosis and survival in older women with endometrial cancer. METHODS: The Surveillance, Epidemiology, and End Results - Medicare Health Outcomes Survey linked database was used to identify 995 women who were at least 65 years old and completed a survey before diagnosis with endometrial cancer. We obtained scores for 10 HRQOL scales, as measured by Medical Outcomes Study Short Form-36 and Veterans RAND 12-Item Survey, and data on activities of daily living (ADLs) impairments and depressive symptoms. Fine and Gray competing risks regression and Cox proportional hazards were used to estimate the association of HRQOL with endometrial cancer-specific and overall survival, respectively. RESULTS: Women who died had worse pre-diagnosis HRQOL than women who were still alive at the end of the study period. For every five-point increase in HRQOL score, overall survival improved by 5-9%. The strongest associations were observed for vitality (HR = 0.91, 95% CI 0.86, 0.97, p = 0.0021) and physical functioning (HR = 0.92, 95% CI 0.87, 0.97, p = 0.0010). ADL impairments were generally not predictive of survival, though depressive symptoms were significantly associated with increased hazard of death from all causes (HR = 1.34, 95% CI 1.00, 1.79, p = 0.0466). CONCLUSION: HRQOL measured before diagnosis with endometrial cancer has prognostic value. Having measures of HRQOL available at diagnosis may facilitate timely supportive care to improve survival.


Assuntos
Neoplasias do Endométrio/mortalidade , Atividades Cotidianas , Idoso , Feminino , Humanos , Medicare/estatística & dados numéricos , Prognóstico , Qualidade de Vida , Programa de SEER , Inquéritos e Questionários , Estados Unidos/epidemiologia
14.
Am J Clin Oncol ; 43(6): 399-410, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32079851

RESUMO

OBJECTIVE: We sought to understand factors associated with refusal of adjuvant radiotherapy in endometrial cancer and its impact on outcomes. METHODS: Data from the National Cancer Database for patients who underwent surgery for nonmetastatic endometrial cancer between 2004 and 2015 were pooled. The Pearson χ test and multivariate logistic regression analyses were used to assess demographic, clinical, and treatment factors. Inverse probability of treatment weighting was used to account for differences in baseline characteristics. Kaplan-Meier analyses and doubly-robust estimation with multivariate Cox proportional hazards modeling were used to analyze overall survival (OS). RESULTS: We identified 4739 of 80,803 patients (5.9%) who refused radiotherapy. Factors associated with refusal were: no insurance (relative risk [RR]=1.66, P<0.01), Medicare (RR=1.42, P<0.01), living >50 miles from treatment (RR=1.34, P<0.01), Charlson-Deyo Comorbidity Scores of 1 (RR=1.16, P<0.01) or ≥2 RR=1.38, P<0.01), age above 60 years (RR=1.28, P<0.01), International Federation of Gynecology and Obstetrics (FIGO) stages IIIA (RR=1.63, P<0.01) and IIIC (RR=1.65, P<0.01) disease, papillary (RR=1.69, P<0.01) and clear cell histology (RR=1.64, P<0.01). Factors associated with radiation therapy receipt included: Hispanic race (RR=0.61, P<0.01), income >$63,000 (RR=0.89, P=0.044), undergoing chemotherapy (RR=0.17, P<0.01), FIGO stages IB (RR=0.81, P<0.01) and II (RR=0.70, P<0.01) disease, and lymphadenectomy (RR=0.79, P<0.01). After weighting, 5-year OS was significantly lower with refusal (74.3% vs. 79.7%, P<0.01). This survival decrement was maintained across FIGO stages. CONCLUSIONS: We identified characteristics associated with radiation refusal, including socioeconomic barriers, advanced disease stage, and histology. Refusal of radiotherapy conferred decreased OS across FIGO stages.


Assuntos
Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/radioterapia , Recusa do Paciente ao Tratamento , Feminino , Humanos , Pessoa de Meia-Idade , Radioterapia Adjuvante , Taxa de Sobrevida
15.
Medicine (Baltimore) ; 99(8): e19281, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080141

RESUMO

BACKGROUND: The aim of this meta-analysis was to assess the clinicopathological features and to confirm prognostic value of POLE exonuclease domain mutations (EDM) in endometrial carcinoma patients. METHODS: The PubMed, Web of Science, the data of China National Knowledge Infrastructure, and Wan fang Medical Network were systematically searched for relevant articles without a cut-off date. The keywords for the search were "endometrial cancer," "endometrial carcinoma," "EC," "POLE mutations," "POLE exonuclease domain mutations," "POLE-mutant," "clinical characteristics" "prognostic." Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by using Review manager 5.3 and Stata 14.0 statistical software. RESULTS: Six cohort studies assessing 179 EC patients with POLE EDMs were included. The results indicated a favorable progression-free survival in POLE-mutant patients (HR = 0.32; 95% CI: = [0.09-1.18]). Furthermore, the overall survival was great in patients with POLE-mutant (HR = 0.68; 95% CI = [0.41-1.13]). It was shown that a significantly higher incidence of POLE mutations with Federation of International of Gynecologists and Obstetricians (FIGO) I group compared to FIGO II-IV group (pooled ORs: 0.34, 95% CI: [0.12-0.94], P = .04), POLE-mutant EC was not significantly associated with histology (OR = 0.56,95% CI: 0.29-1.23), tumor grade (OR = 1.22,95% CI:0.85-1.74), lymph-vascular space invasion (OR = 0.40,95% 0.06-2.42), depth of myometrial invasion (OR = 0.70,95% CI: 0.41-1.18), lymph node status (OR = 0.41, 95% 0.04-4.50), and European Society for Medical Oncology risk groups (OR = 0.68,95% CI: 0.37-1.26). CONCLUSION: This meta-analysis has confirmed POLE EDMs may serve as a predictive biomarker of favorable prognosis. Further studies are needed to explore the appropriate clinical utility of POLE EDMs in EC.


Assuntos
DNA Polimerase II/genética , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , Mutação , Proteínas de Ligação a Poli-ADP-Ribose/genética , Biomarcadores Tumorais/genética , Neoplasias do Endométrio/patologia , Feminino , Humanos , Linfonodos/patologia , Miométrio/patologia , Invasividade Neoplásica , Prognóstico , Intervalo Livre de Progressão
16.
DNA Cell Biol ; 39(4): 615-630, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32105510

RESUMO

Uterine corpus endometrial carcinoma (UCEC) is one of the leading causes of death from gynecological cancer due to the high recurrence rate. A recent study indicated that molecular biomarkers can enhance the recurrence prediction power if they were integrated with clinical information. In this study, we attempted to identify a new multi-RNA-type-based molecular biomarker for predicting the recurrence risk and recurrence-free survival (RFS). Matched mRNA (including lncRNA) and miRNA RNA-sequencing data from 463 UCEC patients (n = 75, recurrent; n = 388, non-recurrent) were downloaded from The Cancer Genome Atlas database. LASSO (least absolute shrinkage and selection operator) analysis was used to screen the optimal combination of prognostic RNAs and then the risk score model was constructed. Moreover, the molecular mechanisms of prognostic RNAs were explored by establishing various interaction networks based on corresponding predictive databases. A multi-RNA-type-based signature (including three miRNAs: hsa-miR-6511b, hsa-miR-184, hsa-miR-4461; three lncRNAs: ENO1-IT1, MCCC1-AS1, AATBC; and 7 mRNAs: EPPK1, ASB9, BDNF, CYP11A1, ECEL1, EN2, F13A1) was developed for the prediction of RFS. The risk scoring system established by these signature genes was effective for the discrimination of the 5-year RFS in the high-risk from low-risk patients in the training [an area under the receiver operating characteristic curve (AUC) = 0.960], validation (AUC = 0.863), and entire datasets (AUC = 0.873). This risk score model was also proved to be a more excellent, independent prognostic discriminator than the single-RNA-type (overall AUC: 0.947 vs. 0.677, lncRNAs; 0.709, miRNAs; 0.899, mRNAs) and clinical staging (overall AUC: 0.947 vs. 0.517). Furthermore, the downstream mechanisms for some prognostic miRNAs or lncRNAs (HAND2-AS1-hsa-miR-6511b-APC2, PAX8-AS1-hsa-miR-4461-TNIK and MCCC1-AS1/ENO1-IT1-TNIK) were newly predicted based on the coexpression or competitive endogenous RNA theories. In conclusion, our findings may provide novel biomarkers for recurrence prediction and targets for treatment of UCEC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Sequência de Bases , Colo do Útero/patologia , Intervalo Livre de Doença , Neoplasias do Endométrio/diagnóstico , Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pessoa de Meia-Idade , Análise de Sequência de RNA
17.
Oncology ; 98(4): 195-201, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32036368

RESUMO

PURPOSE: The objective of this study was to evaluate the impact of hormone replacement therapy (HRT) on the prognosis in endometrial cancer (EC) survivors. METHODS: The research was conducted using the following electronic databases: MEDLINE (PubMed), Web of Science, ClinicalTrial.gov, and Cochrane Library. We performed a review of studies published from January 1986 to January 2019. We selected studies that included EC patients submitted to surgery with curative intent and postoperative use of HRT. RESULT: Seven of 1,332 abstracts considered were eligible: 4 retrospective series, 1 prospective study, 1 randomized controlled trial, and 1 population study. Globally in the observed studies there was not a significant increase in the recurrence rate, measured by the relative risk, in the EC survivors using HRT compared with the controls in tumour stages I and II. The bias was that HRT was prescribed only to low-risk patients, who were young and had a low stage of disease. CONCLUSION: This systematic review shows that HRT use had no negative effect on prognosis in EC survivors in tumour stages I and II.


Assuntos
Sobreviventes de Câncer , Neoplasias do Endométrio/mortalidade , Terapia de Reposição Hormonal , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Humanos , Recidiva Local de Neoplasia/epidemiologia , Prognóstico
18.
Asian Pac J Cancer Prev ; 21(1): 249-254, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31983192

RESUMO

BACKGROUND: This study aimed to survey quality of life (QoL) in endometrial cancer survivors between surgery with adjuvant therapy (radiation with or without chemotherapy) and surgery alone in Thammasat University Hospital, Thailand. MATERIALS AND METHODS: This cross-sectional study was conducted at the Gynecologic Oncology clinic, Thammasat University hospital, Thailand between March 2011 and May 2019. Participants were endometrial cancer cases who underwent surgical staging with or without adjuvant treatment (study) and healthy women who came to gynecologic department for annual cervical screening (control). Assessment of QoL was investigated via the structural questionnaire designed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (Thai version). RESULTS: During the period of the study, 94 participants who were diagnosed with endometrial cancer and underwent surgical staging were enrolled. There were 51, 43 and 51 cases in group A (surgery with adjuvant therapy), group B (surgery only) and group C (control), respectively. Control cases were participants who had comparable demographic characteristics and underwent gynecological checkup during the period of study. In part of physical functioning, group B had statistically better scores than group A. Participant in group B and C reported significantly better QoL in part of social functioning than group A. Symptom severity; appetite loss and constipation in group B was statistically less than in group A. Constipation problems in group A and C were comparable. Participants in group C had worse global health status than group A/B. CONCLUSION: Adjuvant treatment with either radiation or chemotherapy had negative impacts on QoL in endometrial cancer survivors. It impacted physical health, social function, appetite loss, and constipation. All endometrial cancer survivors had global health scores better than healthy peers. Thoroughly counseling to endometrial cancer survivors remains an important tool for increasing awareness of treatment complications and lowering psychological emotional stress.
.


Assuntos
Sobreviventes de Câncer/psicologia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/psicologia , Qualidade de Vida , Saúde da Mulher , Estudos de Casos e Controles , Estudos Transversais , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Seguimentos , Hospitais Universitários , Humanos , Pessoa de Meia-Idade , Prognóstico , Inquéritos e Questionários , Taxa de Sobrevida , Tailândia
19.
Ir J Med Sci ; 189(3): 835-842, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31970616

RESUMO

BACKGROUND: Prognostic value of accompanying adenomyosis in endometrial cancer is the subject of interest due to their common etiology and co-occurrence frequency. However, it is still unclear whether adenomyosis has a role in the prognosis of endometrial cancer. AIMS: The aim of this study was to determine the effects of adenomyosis on the prognosis of patients with endometrial cancer. METHODS: In this study, medical records of 552 patients with endometrioid endometrial cancer who underwent surgery between 2007 and 2017 were retrospectively reviewed. The patients were divided into two groups based on the presence or absence of adenomyosis, and these two groups were compared in terms of the clinicopathological factors and survival outcomes of patients. RESULTS: Of these patients, 103 (18.7%) had adenomyosis, and the remaining 449 (81.3%) did not. The endometrial cancer patients with adenomyosis exhibited earlier stages (p < 0.001), lower tumor grades (p < 0.001), tumor sizes ≤ 2 cm (p = 0.002), myometrial invasion < 50% (p < 0.001), and negative lymphovascular space invasion (p < 0.001). The 5-year overall survival rate was comparable between the adenomyosis and non-adenomyosis groups (95 vs. 89.1%, respectively; p = 0.085). The presence of adenomyosis was significantly associated with a higher 5-year disease-free survival rate (95.1 vs. 87.9%; p = 0.047), but adenomyosis did not remain as a prognostic factor in multivariate analysis. CONCLUSION: The results of our study showed that the endometrioid endometrial cancer patients with adenomyosis are significantly associated with smaller tumor sizes, less myometrial invasion, lower tumor grades, less lymphovascular space invasion, and earlier FIGO stages. Nevertheless, adenomyosis was not found to be an independent prognostic factor for endometrioid endometrial cancer.


Assuntos
Neoplasias do Endométrio/complicações , Adenomiose/complicações , Adenomiose/mortalidade , Adenomiose/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
20.
Am J Surg Pathol ; 44(2): 174-181, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31651527

RESUMO

Programmed death-ligand 1 (PD-L1) is a biomarker that may predict the response to anti-programmed death 1/PD-L1 immunotherapy. We evaluated the expression of PD-L1 in carcinoma cells (Ca) and immune cells (ICs) across histopathologic and The Cancer Genome Atlas (TCGA) molecular subgroups of endometrial carcinoma (EC). Our study included 842 patients with EC. Direct sequencing of polymerase epsilon (POLE) exonuclease domain hot spots and conventional immunohistochemistry (MLH1, PMS2, MSH2, MSH6, p53) were conducted to identify TCGA classification-based molecular subgroups of EC: POLE-mutated, mismatch repair deficient, no specific molecular profile, and p53 aberrant. Multiplex immunohistochemistry was performed to evaluate PD-L1 expression in Ca and tumor-infiltrating ICs. PD-L1 expression in Ca and in ICs was detected in 8.6% and 27.7% of the cases, respectively. A combined positive score (CPS) was ≥1% in 19.4% of the samples. PD-L1 positivity in Ca and ICs, and CPS correlated with tumor T-cell density (P<0.001). POLE-mutated and mismatch repair-deficient tumors were more likely to present PD-L1-expressing ICs, CPS positivity, and abundant tumor-infiltrating lymphocytes compared with other TCGA subgroups (P<0.001). No differences existed in Ca-PD-L1 expression (P=0.366). Within various histotypes, non-endometrioid carcinomas displayed the highest Ca-PD-L1, ICs, and CPS (P<0.03). Advanced cancers showed more frequent Ca-PD-L1 positivity (P=0.016), and CPS (P=0.029) and IC≥1% (P=0.037) positivity compared with early disease. In conclusion, PD-L1 expression profiles differ between molecular subclasses, histologic subtypes, and disease stage of EC. Prospective studies are needed to explore the predictive value of various PD-L1 scoring systems within the subgroups of EC. CPS presents methodological advantages over cell type-specific scoring systems.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma/metabolismo , Neoplasias do Endométrio/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Idoso , Carcinoma/mortalidade , Carcinoma/patologia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Serial de Tecidos
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