Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.201
Filtrar
1.
Rio de Janeiro; s.n; 20200100. 28 p. ilus.
Monografia em Português | Coleciona SUS | ID: biblio-1049867

RESUMO

"O Carcinoma Dediferenciado do Endométrio (DDEC) é uma neoplasia constituída por dois componentes histológicos morfologicamente distintos (diferenciado e indiferenciado). O componente diferenciado corresponde a um carcinoma endometrioide de baixo grau (I ou II), enquanto o componente indiferenciado é caracterizado por células epiteliais homogêneas de tamanho médio, sem qualquer tipo de diferenciação ou padrão morfológico arquitetural. Esta neoplasia foi descrita inicialmente em 2006, mas somente em 2014 foi incluída na classificação dos tumores da Organização Mundial de Saúde (OMS). Por ser uma entidade relativamente nova e ainda desconhecida por parte de alguns patologistas, estimase que o DDEC seja subdiagnosticado. O componente indiferenciado pode ser confundido com área sólida de um carcinoma endometrioide grau III ou mesmo com outras entidades tais como tumores neuroendócrinos, sarcomas ou linfomas. O estudo imuno-histoquímico e molecular contribui para confirmação do diagnóstico. Este trabalho tem como objetivo revisar a literatura recente do DDEC para melhor caracterização dos seus aspectos clínicopatológicos, já que esta neoplasia tem um pior prognóstico quando comparado com os carcinomas endometrioides e serosos uterinos."(AU)


"Dedifferentiated Endometrial Carcinoma (DDEC) is a neoplasm consisting of two morphologically distinct histological components (differentiated and undifferentiated). The differentiated component corresponds to a low grade endometrioid carcinoma (I or II), while the undifferentiated component is characterized by homogeneous epithelial cells of medium size, without any kind of differentiation or architectural morphological pattern. This neoplasm was first described in 2006, but only in 2014 it was included in the World Health Organization (WHO) classification of tumors. Because it is a relatively new entity and still unknown to some pathologists, it is estimated that DDEC is underdiagnosed. The undifferentiated component can be confused with the solid area of a grade III endometrioid carcinoma or even with other entities such as neuroendocrine tumors, sarcomas or lymphomas, and immunohistochemical and molecular study contribute to confirmation of the diagnosis. This paper aims to review the recent literature of DDEC to better characterize its clinical and pathological aspects, since this neoplasia has a worse prognosis when compared to endometrioid and serous uterine carcinomas." (AU)


Assuntos
Humanos , Feminino , Carcinoma Endometrioide/patologia , Carcinoma/patologia
2.
Gynecol Oncol ; 156(1): 154-161, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759772

RESUMO

OBJECTIVE: Adjuvant management of women with high-intermediate- and high-risk early-stage endometrial cancer remains controversial. Recently published results of GOG 249 revealed that vaginal brachytherapy plus chemotherapy (VBT + CT) was not superior to whole pelvic radiation therapy (WPRT) and was associated with more toxicities and higher nodal recurrences. This study examined off-study utilization of VBT + CT among women who met criteria for GOG 249 in the period prior to study publication. METHODS: Women diagnosed with FIGO IA-IIB endometrioid, serous, or clear cell uterine cancer between 2004-2015 and treated with hysterectomy and radiotherapy (RT) were identified in the National Cancer Database. Cochrane-Armitrage trend test was used to assess trends over time. Univariate and multivariate Cox analyses were performed to calculate odds ratio (OR) of VBT + CT receipt and hazard ratio (HR) of OS. Propensity-score matched analysis was conducted to account for baseline differences. RESULTS: 9956 women met inclusion criteria. 7548 women (75.8%) received WPRT while 2408 (24.2%) received VBT + CT in the study period. From 2004-2015, there was a significant increase in VBT + CT use (p < 0.001) with the largest overall increase occurring in 2009 to 22%. Factors significantly associated with VBT + CT receipt included higher socioeconomic status (p < 0.001), higher grade endometrioid cancer (p < 0.001), and aggressive histology (p < 0.001). After propensity-score matching, VBT + CT was associated with improved OS (HR 0.74, 95% CI 0.58-0.93); however, when stratified by FIGO stage, VBT + CT was only associated with improved OS for FIGO stage 1B (HR 0.62, 95% CI 0.44-0.87). CONCLUSIONS: There was significant use of experimental arm off-study treatment in the United States prior to report of GOG 249 results. Providers should be cautious when offering off-study treatment utilizing an experimental regimen given uncertainty about efficacy and toxicity.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/radioterapia , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/radioterapia , Adenocarcinoma de Células Claras/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/métodos , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/radioterapia , Carcinoma Endometrioide/cirurgia , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/radioterapia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Adulto Jovem
3.
Gynecol Oncol ; 156(1): 251-259, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31767187

RESUMO

The majority of endometrial cancers are detected early with a favourable prognosis. However, for patients with advanced disease, chemotherapy response rates and overall survival remains poor. The endometrial cancer population is typically elderly with multiple co-morbidities and aggressive cytotoxic therapy may be hazardous. Therefore, there is an urgent need to define optimal treatment strategies for advanced and recurrent disease and personalise therapy based on individual tumour and patient characteristics. Three-dimensional (3D) models that preserve the tumour microenvironment and tumour-stromal interactions are increasingly important for translational research with the advent of immunotherapy and molecularly targeted agents. 3D patient-relevant pre-clinical models in endometrial cancer include spheroids, patient-derived organoids, microfluidic systems, patient-derived xenografts and patient-derived explants. Here we present a review of available 3D modelling systems in endometrial cancers, highlighting their current use, advantages, disadvantages and applications to translational research with a focus on the power of the patient-derived explant platform.


Assuntos
Técnicas de Cultura de Células/métodos , Neoplasias do Endométrio/patologia , Animais , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/patologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Xenoenxertos , Humanos , Transplante de Neoplasias/métodos , Organoides/patologia , Esferoides Celulares/patologia , Pesquisa Médica Translacional/métodos
4.
Gynecol Oncol ; 156(1): 194-202, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31757464

RESUMO

OBJECTIVES: Assess outcomes of a clinical cohort of patients with endometrioid endometrial cancer (EEC) harboring somatic POLE exonuclease domain mutations (EDMs). METHODS: Patients were consented to a protocol of tumor-normal massively parallel sequencing of 410-468 cancer related genes. EECs subjected to sequencing from 2014 to 2018 were reviewed. Tumors with somatic POLE EDMs were identified. EECs were assessed for microsatellite instability (MSI) using MSIsensor and immunohistochemical analysis for mismatch repair (MMR) proteins. RESULTS: Of the 451 EECs sequenced, 23 had a POLE EDM (5%): 20 primary and 3 recurrent tumors sequenced. Nineteen cases (83%) were stage I/II and 4 (17%) were stages III/IV. Thirteen EECs (57%) were of FIGO grades 1/2, 10 (43%) grade 3. All patients were treated with surgery and 17 (89%) received adjuvant therapy. Five (22%) demonstrated loss of DNA MMR protein expression, none were due to Lynch syndrome. MSIsensor scores were conclusive for 21 samples: 19 were microsatellite stable and 2 MSI-high. After median follow-up of 30 months, 4/23 (17%) developed recurrences: 3 with initial grade 3 stage I and 1 with grade 1 stage III disease. One patient with grade 2 stage IV EEC had progressive disease after treatment. CONCLUSIONS: Patients with POLE EDM EEC have been shown to have a favorable prognosis. In this real-world cohort of patients, de novo metastatic disease and recurrences in initially uterine-confined cases were observed. Further research is warranted before incorporating the presence of POLE EDM into decision-making regarding adjuvant therapy.


Assuntos
Carcinoma Endometrioide/genética , DNA Polimerase II/genética , Neoplasias do Endométrio/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Adulto , Idoso , Carcinoma Endometrioide/enzimologia , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/terapia , Estudos de Coortes , Reparo de Erro de Pareamento de DNA , DNA Polimerase II/metabolismo , Neoplasias do Endométrio/enzimologia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Metástase Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Prognóstico , Estudos Prospectivos
5.
Gynecol Oncol ; 155(3): 429-435, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31610885

RESUMO

OBJECTIVE: To report on patterns of care as well as evaluate the two treatment regimens using a large retrospective hospital-based registry to identify possible subgroups of patients who may experience benefit with VBT + CT vs. EBRT. METHODS: Patients from the National Cancer Database (NCDB) were identified who met the inclusion criteria for GOG 249 and were treated with either VBT + CT or WPRT. Demographic, clinicopathologic, and treatment factors were collected. Association of treatment type and other variables with overall survival was analyzed using Cox proportional hazards model. Subset analyses were performed based on a variety of risk factors, including high risk pathologies, surgical nodal sampling, and grade. RESULTS: A total of 4,602 patients were included in the analysis, with 41% receiving VBT + CT and 59% receiving WPRT. For the entire cohort, VBT + CT was associated with improved survival, with 3-year overall survival 89.6% vs. 87.8% (hazard ratio 1.24, 95%CI 1.01-1.52, p = 0.04). On subset analysis, patients with serous histology experienced benefit with VBT + CT, while high-grade endometrial patients without lymph node dissection experienced improved survival associated with EBRT. After exclusion of serous histology, there was no survival difference associated with treatment type. CONCLUSIONS: VBT + CT was associated with superior survival outcomes in patients with early-stage serous carcinoma. For non-serous histology, treatment modality was not associated with a difference in survival, although patients with high-grade disease and no nodal dissection experienced benefit from EBRT.


Assuntos
Braquiterapia/métodos , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/radioterapia , Idoso , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/radioterapia , Quimiorradioterapia , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/radioterapia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Fatores de Risco , Resultado do Tratamento
6.
Pathologe ; 40(6): 609-618, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31578630

RESUMO

Dedifferentiated endometrial carcinomas (ECs) are composed of undifferentiated EC and a FIGO grade 1 or 2 endometrioid carcinoma. The undifferentiated component represents a malignant epithelial neoplasm with no obvious differentiation and immunohistochemical loss of PAX8, E­cadherin and focal expression of EMA and/or CK18 and the predominant presence of nuclear staining for INI1 (SMARCB1) and BRG1 (SMARCA4). The main differential diagnoses include poorly differentiated endometrioid EC, neuroendocrine carcinoma, lymphoma, plasmocytoma, high-grade endometrial stromal sarcomas, undifferentiated uterine sarcomas (UUS), carcinosarcomas, and metastases to the endometrium. The histogenesis is not yet fully understood and molecular data are still limited. Some tumors represent a loss of MHL1 and PMS2 staining due to MLH1-promotor methylation. Rare cases are associated with Lynch syndrome or POLE mutation. The un- or dedifferentiated EC represents a high-grade endometrial carcinoma that requires extended surgery and indicates a poor prognosis. In cases with mismatch repair protein deficiency or POLE mutation, immuno-oncological treatment with checkpoint inhibitors are a therapeutic option.


Assuntos
Carcinoma Endometrioide , Carcinossarcoma , Neoplasias do Endométrio , Biomarcadores Tumorais , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/patologia , Carcinossarcoma/diagnóstico , Carcinossarcoma/patologia , Diagnóstico Diferencial , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica
7.
Zhonghua Fu Chan Ke Za Zhi ; 54(9): 595-600, 2019 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-31550775

RESUMO

Objective: To investigate the clinicopathological characteristics and significance of solid, endometrioid and transitional (SET) ovarian high-grade serous carcinoma (HGSC). Methods: A total of 408 cases of ovarian HGSC admitted to Peking University People's Hospital from January 2011 to September 2016 were collected. (1) According to the proportion of tumors with SET form in all tumors, they were divided into three groups: HGSC-classic group (<25%), HGSC-SET Ⅰ (25%-50%) and HGSC-SET Ⅱ (>50%) group. The clinical and pathological characteristics of three groups of ovarian HGSC patients were compared respectively. (2) According to the growth pattern, that was, the proportion of pushing/expanding invasive tumors in the whole pelvic disseminated tumors of pelvic disseminated tumors, the three groups were divided into four subgroups: group A (0-25%), group B (26%-50%), group C (51%-75%) and group D (>75%). Differences in progression-free survival (PFS) among the four subgroups in each group were compared respectively. Results: The median age of 408 cases with ovarian HGSC was 63.3 years (47-78 years), including 152 cases premenopausal and 256 cases postmenopausal. Among 408 cases of ovarian HGSC, 290 cases were in HGSC-classic group, 91 cases in HGSC-SET Ⅰ and 27 cases in HGSC-SET Ⅱ group. (1) There were significant differences in age, proportion of menopausal patients, tumor necrosis (including map necrosis or acne necrosis), response rate to primary chemotherapy, 5-year mortality rate and PFS between HGSC-SET Ⅰ and HGSC-SET Ⅱ (P<0.05). There was no significant difference among the above indexes between HGSC-SET Ⅰ and HGSC-SET Ⅱ (P>0.05). In HGSC-classic group, HGSC-SET Ⅰ and HGSC-SET Ⅱ, the proportion of family members or patients with history of epithelial ovarian cancer or breast cancer increased in turn, and the detection rate of serous tutal intraepithelial carcinoma (STIC) in fallopian tube tissue decreased in turn. There were significant differences between the two groups (P<0.05). (2) In HGSC-classic group, there were 147 cases in group A, 124 cases in group B and 19 cases in group C (0 case in group D), with median PFS of 17.4, 17.7 and 16.5 months respectively (P<0.05); 10, 6, 29 and 46 cases in group A, B, C and D in HGSC-SET Ⅰ, with median PFS of 9.6, 12.7, 30.1 months and 39.0 months respectively, which there were significant difference among group A and C and D (all P<0.05); among group B, C and D group in HGSC-SET Ⅱ, there were respectively 3, 12 and 12 cases (0 case in group A), and the median PFS was 13.5, 34.2 and 47.8 months (P<0.05). PFS was positively correlated with the increase of push/expansive infiltration ratio. Conclusions: The detection rate of STIC in ovarian HGSC patients with SET is higher, the effect of primary chemotherapy is better, and PFS is prolonged. PFS was significantly prolonged in patients with pelvic disseminated tumors of HGSC-SET, the infiltration of which were predominated by pushing or expanding boarder.


Assuntos
Carcinoma Endometrioide/patologia , Cistadenocarcinoma Seroso/patologia , Neoplasias Ovarianas/patologia , Idoso , Carcinoma in Situ , Carcinoma Endometrioide/mortalidade , China/epidemiologia , Cistadenocarcinoma Seroso/mortalidade , Neoplasias das Tubas Uterinas , Tubas Uterinas , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Índice de Gravidade de Doença
8.
Int J Mol Sci ; 20(15)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370215

RESUMO

Dedifferentiated endometrial carcinoma (DDEC) is defined as an undifferentiated carcinoma admixed with differentiated endometrioid carcinoma (Grade 1 or 2). It has poor prognosis compared with Grade 3 endometrioid adenocarcinoma and is often associated with the loss of mismatch repair (MMR) proteins, which is seen in microsatellite instability (MSI)-type endometrial cancer. Recent studies have shown that the effectiveness of immune checkpoint inhibitor therapy is related to MMR deficiency; therefore, we analyzed the immunophenotype (MMR deficient and expression of PD-L1) of 17 DDEC cases. In the undifferentiated component, nine cases (53%) were deficient in MMR proteins and nine cases (53%) expressed PD-L1. PD-L1 expression was significantly associated with MMR deficiency (p = 0.026). In addition, the presence of tumor-infiltrating lymphocytes (CD8+) was significantly associated with MMR deficiency (p = 0.026). In contrast, none of the cases showed PD-L1 expression in the well-differentiated component. Our results show that DDEC could be a target for immune checkpoint inhibitors (anti PD-L1/PD-1 antibodies), especially in the undifferentiated component. As a treatment strategy for DDEC, conventional paclitaxel plus carboplatin and cisplatin plus doxorubicin therapies are effective for those with the well-differentiated component. However, by using immune checkpoint inhibitors in combination with other conventional treatments, it may be possible to control the undifferentiated component and improve prognosis.


Assuntos
Anticorpos Neutralizantes/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Idoso , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Carboplatina/uso terapêutico , Carcinoma/genética , Carcinoma/imunologia , Carcinoma/patologia , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/imunologia , Carcinoma Endometrioide/patologia , Cisplatino/uso terapêutico , Reparo de Erro de Pareamento de DNA/efeitos dos fármacos , Doxorrubicina/uso terapêutico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/patologia , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Linfócitos do Interstício Tumoral , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/uso terapêutico , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia
9.
Eur J Obstet Gynecol Reprod Biol ; 240: 310-315, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31377459

RESUMO

OBJECTIVE: The purpose of this study was to develop a risk assessment index that could determine which endometrioid endometrial cancer (EC) patients would benefit from a lymphadenectomy. METHODS: The final pathology reports of 353 women who underwent complete surgical staging, including pelvic and para-aortic lymphadenectomy, for endometrioid EC between January 2008 and June 2018 were retrospectively reviewed. A logistic regression was used to investigate the clinicopathological factors associated with a positive nodal status. The independent risk factors for lymphatic dissemination were used to build a risk model and a "Lymph Node (LN) Metastasis Risk Index" was defined as follows: (tumor grade) × (primary tumor diameter) × (percentage of myometrial invasion) × (preoperative serum CA 125 level). The scores used in the LN Metastasis Risk Index were weighted according to the odds ratios assigned for each variable. The diagnostic performance of the model was expressed as the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio. RESULTS: The LN Metastasis Risk Index correctly identified 35 of 40 LN-positive women at a cutoff point of 981.0 (sensitivity: 87.5%, specificity: 86.3%, negative predictive value: 98.2%, positive predictive value: 44.9%, positive likelihood ratio: 6.37, and negative likelihood ratio: 0.14). The area under the receiver operating characteristic curve was 0.90 (95% confidence interval = 0.858-0.947) at this cutoff. The clinical accuracy of the model was 86.4%. When a cutoff point of <981.0 was selected in order to define those women at low-risk for lymphatic dissemination, our prediction model classified 275 women (77.9%) as being at low-risk for nodal involvement. Among these 275 women, 5 actually had positive LNs, which indicated a 1.8% false-negative rate. CONCLUSION: After external validation, the LN Metastasis Risk Index may be a valuable tool for the surgical management of endometrioid EC.


Assuntos
Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/patologia , Metástase Linfática/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Vasos Linfáticos/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Medição de Risco
10.
Gynecol Oncol ; 155(1): 21-26, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31409487

RESUMO

OBJECTIVE: To compare two published risk stratification models (Milwaukee Model vs. Mayo Criteria) to predict lymphatic dissemination (LD) in endometrioid endometrial cancer (EC). METHODS: Patients with stage I-III EC undergoing surgery from 1/1/2004-9/30/2013 were retrospectively reviewed and classified as low-risk vs at-risk for LD using two independent risk models. LD was defined as positive nodes at surgery or lymph node recurrence within 2 years of surgery after negative lymph node dissection (LND) or when LND was not performed. False positive (FP) and false negative (FN) rates for each risk model were calculated. RESULTS: Among 1103 patients, 81 (7.3%) had LD (72 positive LN and 9 LN recurrences), and most (90.2%) had stage I EC. The Milwaukee Model yielded a low at-risk rate for LD (38.1%) but a high FN rate (13.6%, 95% CI 7.0-23.0). The traditional Mayo Criteria using a cut-off of 2 cm for tumor diameter (TD) had a higher at-risk rate for LD (69.5%) but a FN rate of 0% (95% CI, 0-4.5). Modifying the Mayo Criteria using a TD cutoff of ≤3 cm identified fewer women at-risk (56.8% vs. 69.5%) and had a lower FP rate (53.6% vs. 67.1%), but had a higher FN rate (3.7%, 95% CI, 0.8-10.4). CONCLUSIONS: The Milwaukee Model had the lowest at-risk rate of LD but an unacceptable FN rate. Modifying the Mayo Criteria by increasing the TD cutoff from the traditional ≤2 cm to ≤3 cm would spare an estimated 13.5% of patients LND, but the accompanying FN rate is unacceptably high. The traditional Mayo Criteria for low-risk EC remains the most sensitive in determining which patients LND can be omitted.


Assuntos
Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Estudos de Coortes , Reações Falso-Negativas , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Modelos Estatísticos , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Retrospectivos , Risco , Biópsia de Linfonodo Sentinela
11.
BMC Cancer ; 19(1): 810, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412816

RESUMO

BACKGROUND: Endometrial cancer is the most common gynecological cancer. G-protein coupled receptor 64 (GPR64) belongs to a family of adhesion GPCRs and plays an important role in male fertility. However, the function of GPR64 has not been studied in endometrial cancer. Our objective is to investigate the role of GPR64 in endometrial cancer. METHODS: We examined the levels of GPR64 in human endometrioid endometrial carcinoma by immunohistochemistry analysis. To determine a tumor suppressor role of GPR64 in endometrial cancer, we used a siRNA loss of function approach in human endometrial adenocarcinoma cell lines. RESULTS: GPR64 levels were remarkably lower in 10 of 21 (47.62%) of endometrial carcinoma samples compared to control. Depletion of GPR64 by siRNA transfection revealed an increase of colony formation ability, cell proliferation, cell migration, and invasion activity in Ishikawa and HEC1A cells. The expression of Connexin 43 (Cx43), a member of the large family of gap junction proteins, was reduced through activation of AMP-activated protein kinase (AMPK) in Ishikawa cells with GPR64-deficicy. CONCLUSIONS: These results suggest that GPR64 plays an important tumor suppressor role in endometrial cancer.


Assuntos
Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/patologia , Receptores Acoplados a Proteínas-G/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Conexina 43/metabolismo , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Fosforilação , RNA Interferente Pequeno , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Receptores Acoplados a Proteínas-G/genética
12.
Anticancer Res ; 39(8): 4143-4147, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366499

RESUMO

BACKGROUND/AIM: Vitamin D analogs have a protective effect on carcinogenesis in humans. Since vitamin D receptor (VDR) is detected in many histotypes of cancer, this study evaluated the role of VDR expression in endometrioid carcinoma. MATERIALS AND METHODS: Tumor samples were collected from 60 patients who had undergone surgery, and the pattern of VDR expression assessed in tissue microarray (TMA) blocks of tumor samples. When VDR expression in the cytoplasm was higher than that in the nucleus, this was noted as 'displacement'. Using statistical analysis, the relationship between VDR expression and clinicopathological factors was evaluated. RESULTS: Immunohistochemical staining of nuclear VDR was as follows: Negative: 32 (53.3%); mild: 13 (21.7%); moderate: 14 (23.3%); strong: 1 (1.7%). For cytoplasmic VDR expression: Negative: 2 (3.3%); mild: 19 (31.7%); moderate: 31 (51.7%); strong: 7 (11.7%). VDR displacement was found in 42 (70%) cores. VDR displacement was significantly positively correlated with endometrioid carcinoma having lower histological grade (1, p=0.03). CONCLUSION: Displacement of VDR was significantly correlated with lower histological grade. Clinicians might be able to predict prognosis and decide therapies related to vitamin D analogs using this remarkable biomarker for endometrial carcinoma.


Assuntos
Carcinogênese/genética , Carcinoma Endometrioide/genética , Prognóstico , Receptores de Calcitriol/genética , Adulto , Idoso , Carcinoma Endometrioide/patologia , Citoplasma/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Análise Serial de Tecidos , Vitamina D/genética
13.
Medicina (Kaunas) ; 55(9)2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466367

RESUMO

Background and objectives: Endometrial polyps in asymptomatic postmenopausal women are often incidentally found, yet only 1.51% of them are malignant. Their potential for malignant transformation has not been adequately addressed. The aim of this study was to investigate the proliferation within endometrial polyps as one of the indicators of their malignization potential in asymptomatic postmenopausal women. Materials and Methods: Immunohistochemical studies of Ki-67 were performed. Cases included 52 benign postmenopausal polyps, 19 endometrioid carcinoma with coexisting benign polyps, 12 polyps with foci of carcinoma and 4 cases of polyps, which later developed carcinoma. The control group included 31 atrophic endometria and 32 benign premenopausal polyps. Ki-67 was scored in either 10 or 20 "hot spot" fields, as percentage of positively stained cells. Results: The median epithelial Ki-67 score in postmenopausal benign polyps (4.7%) was significantly higher than in atrophic endometria (2.41%, p < 0.0001) and significantly lower than in premenopausal benign polyps (11.4%, p = 0.003) and endometrial cancer (8.3%, p < 0.0001). Where endometrial polyps were found in association with endometrial carcinoma, Ki-67 was significantly higher in cancer (p < 0.0001). No significant difference was found between Ki-67 scores of cancer focus and of the polyps tissue itself, respectively 2.8% and 4.55%, p = 0.37. Ki-67 expression, where polyps were resected and women later developed cancer, was not significantly different (p = 0.199). Conclusion: Polyps from asymptomatic postmenopausal women showed significantly more proliferation in both epithelial and stromal components than inactive atrophic endometria but less than premenopausal benign polyps and/or endometrial cancer. Benign postmenopausal endometrial polyps exhibit low proliferative activity, suggesting low malignant potential and may not require resection in asymptomatic women.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Endometrioide/patologia , Transformação Celular Neoplásica/patologia , Neoplasias do Endométrio/patologia , Antígeno Ki-67/metabolismo , Pólipos/patologia , Doenças Uterinas/patologia , Idoso , Proliferação de Células , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Retrospectivos , Doenças Uterinas/metabolismo
15.
Gynecol Oncol ; 154(3): 487-494, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31257010

RESUMO

OBJECTIVES: To determine which patients with locoregionally advanced endometrial cancer may benefit from pelvic external beam radiotherapy (EBRT) in addition to chemotherapy compared to chemotherapy alone. METHODS: Patients with FIGO stages III-IVA endometrial carcinoma between 2004 and 2016 who underwent at least total hysterectomy and adjuvant multiagent chemotherapy were identified in the National Cancer Database. The primary outcome was overall survival according to receipt of pelvic EBRT, analyzed using the Kaplan-Meier method and Cox multivariable regression. RESULTS: In total, 13,270 patients were identified (62% pure endometrioid, 38% serous/clear cell or mixed histology; 22.6% stage IIIA, 4.7% stage IIIB, 71.2% stage IIIC, 1.5% stage IVA), of whom 40% received pelvic EBRT. In univariable analysis, EBRT was associated with absolute 5-year survival increases of 5% and 9% in the endometrioid and non-endometrioid cohorts, respectively (P < 0.0001). In multivariable analyses stratified by stage and histology, patients with a significant benefit from EBRT were stage IIIC (specifically IIIC2) endometrioid (adjusted hazard ratio [HR] 0.73, P = 0.01) and stages IIIB and IIIC non-endometrioid (adjusted HR 0.52, P = 0.01 and adjusted HR 0.79, P < 0.0001). The benefit of EBRT in node-positive patients persisted in those who underwent more extensive lymphadenectomy. CONCLUSIONS: Stages III-IVA endometrial cancer comprised a heterogeneous population with respect to the added benefit of radiotherapy compared to chemotherapy alone. Patients with stage IIIC2 endometrioid and stages IIIB-C non-endometrioid cancer may be most likely to benefit from pelvic EBRT.


Assuntos
Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/terapia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Braquiterapia , Carcinoma Endometrioide/patologia , Quimioterapia Adjuvante , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Sistema de Registros , Estados Unidos/epidemiologia
16.
JSLS ; 23(2)2019.
Artigo em Inglês | MEDLINE | ID: mdl-31285650

RESUMO

Background and Objectives: To determine if the use of an intrauterine manipulator is associated with an increased incidence of pseudovascular invasion on pathologic evaluation of hysterectomy specimens for endometrial cancer and to assess the possible implications of pseudovascular space invasion in the treatment of endometrial cancer. Methods: We performed a retrospective cohort study of patients with early stage (I/II) endometrial cancer who underwent minimally invasive surgical staging. The following data were abstracted: race, body mass index, grade, age, stage, histology, presence or absence of lymphovascular space invasion (LVSI), peritoneal cytology, and adjuvant treatment. Slides were blindly reviewed by a gynecologic pathologist. Results: Of the104 patients meeting eligibility criteria, 74 cases were reviewed in detail (the study was terminated early based on the results of an interim analysis). Patients in the no-manipulator group were older (P = .02) and had a higher stage 1B/II (P = .01) than patients in the manipulator group. No difference was found in the incidence of pseudovascular invasion between the manipulator and the no-manipulator groups (P = .86). Subgroup analysis showed no association of pseudovascular invasion with tumor grade (P = .79). Five patients were identified to have pseudovascular invasion misdiagnosed as true LVSI-4 had endometrioid and 1 had serous histology. Of these, 3 were in the manipulator group. Two received adjuvant radiotherapy which they not have gotten, absent reported lymphovascular invasion. Conclusion: The use of a uterine manipulator does not appear to increase the rate of pseudovascular invasion in our limited data set. Misdiagnosis of pseudovascular invasion as LVSI can result in risk migration of patients with potential for harm from unwarranted adjuvant therapy.


Assuntos
Carcinoma Endometrioide/cirurgia , Carcinossarcoma/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Histerectomia , Laparoscopia , Idoso , Carcinoma Endometrioide/patologia , Carcinossarcoma/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos
17.
Artigo em Inglês | MEDLINE | ID: mdl-31323767

RESUMO

Adjuvant treatment in advanced-stage (stages III /IV) endometrial carcinomas in terms of tumor grades has not yet been explored. We retrospectively analyzed 194 patients with advanced-stage endometrioid endometrial carcinoma who received surgery, followed by adjuvant therapy, at National Taiwan University Hospital between January 1, 2000 and August 31, 2017. Adjuvant therapies included radiation (RT), chemotherapy alone (CT), and combined modality treatment (CMT: radiation and chemotherapy). The prognostic factors were determined from multivariate survival analyses using Cox regression models. Progression-free survival (PFS) and overall survival (OS) times were estimated with the Kaplan-Meier method. The median follow-up was 45.5 months (range: 6.2-207.9). In grade 1/2 endometrioid carcinoma, neither adjuvant CT nor CMT could prolong PFS significantly compared to RT (CT: HR 1.59, 95% CI 0.64-3.97; CMT: HR 2.03, 95% CI 0.72-5.74). Notably, maximal cytoreduction independently improved PFS (HR 0.31, 95% CI 0.10-0.90). No particular adjuvant treatment provided an OS advantage over the others for grade 1/2 endometrioid carcinomas. However, for grade 3 endometrioid carcinoma, CMT showed OS benefits (HR 0.15, 95% CI 0.03-0.89) compared to RT and CT. In conclusion, maximal cytoreduction should be the goal in patients with grade 1/2 advanced-stage endometrioid carcinomas. Based on our results, patients with grade 3 endometrioid carcinomas might benefit from adjuvant CMT.


Assuntos
Carcinoma Endometrioide/terapia , Neoplasias do Endométrio/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Quimioterapia Adjuvante , Terapia Combinada , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Taiwan/epidemiologia , Útero/patologia
18.
Eur J Obstet Gynecol Reprod Biol ; 240: 220-225, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31326637

RESUMO

OBJECTIVE: To test the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) and determine the frequency of specific/prognostic molecular alterations within a cohort of endometrial cancer (EC) women conservatively treated by combined hysteroscopic resection and progestin therapy. STUDY DESIGN: We used blocks of formalin-fixed paraffin-embedded tissue from the primary tumors of patients enrolled into the ECCo trial (EudraCT 2010-018581-23) between 2007 and 2016. In order to assign EC resectoscopic specimens to one of four ProMisE subgroups, testing involved sequential assessment of i) immunohistochemistry (IHC) for mismatch repair (MMR) proteins MLH1, MSH2, MSH6 and PMS2; ii) sequencing for POLE/POLD1 exonuclease domain mutations (EDMs); iii) p53 IHC. RESULTS: Molecular analysis methods were used in 25 patients (stage IA, G1-2 endometrioid EC), of whom 15 (60%) represented fully evaluable cases. Seven cases (46.7%) had abnormal MMR IHC, POLE/POLD1 EDMs were found in 3 cases (20%), and abnormal p53 IHC in 1 case (6.6%). Three patients (20%) had more than one molecular feature. Among 10 (40%) 'unclassifiable' patients, six failures in achieving complete molecular categorization were due to the low tumor volume. Molecular classification of the 15 fully evaluable cases yielded the following ProMisE subtypes: 7 (46.7%) MMR IHC abnormal, 1 (6.6%) POLE EDM, 0 (0%) p53 IHC abnormal, 7 (46.7%) p53 IHC wild-type. CONCLUSIONS: Although larger series are needed to further assess the feasibility of a molecular categorization in a fertility-sparing setting, data presented are promising. In women with early stage low-volume disease, operative hysteroscopy could be advantageous to provide samples allowing complete genetic risk assessment.


Assuntos
Carcinoma Endometrioide/terapia , Neoplasias do Endométrio/terapia , Histeroscopia/métodos , Progestinas/uso terapêutico , Adulto , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia , Tratamento Conservador , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Preservação da Fertilidade , Humanos , Prognóstico , Medição de Risco , Resultado do Tratamento
19.
Gynecol Oncol ; 154(3): 516-523, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31340883

RESUMO

OBJECTIVE: Endometrioid ovarian carcinomas (EOCs) comprise 5-10% of all ovarian cancers and commonly co-occur with synchronous endometrioid endometrial cancer (EEC). We sought to examine the molecular characteristics of pure EOCs in patients without concomitant EEC. METHODS: EOCs and matched normal samples were subjected to massively parallel sequencing targeting 341-468 cancer-related genes (n = 8) or whole-genome sequencing (n = 28). Mutational frequencies of EOCs were compared to those of high-grade serous ovarian cancers (HGSOCs; n = 224) and EECs (n = 186) from The Cancer Genome Atlas, and synchronous EOCs (n = 23). RESULTS: EOCs were heterogeneous, frequently harboring KRAS, PIK3CA, PTEN, CTNNB1, ARID1A and TP53 mutations. EOCs were distinct from HGSOCs at the mutational level, less frequently harboring TP53 but more frequently displaying KRAS, PIK3CA, PIK3R1, PTEN and CTNNB1 mutations. Compared to synchronous EOCs and pure EECs, pure EOCs less frequently harbored PTEN, PIK3R1 and ARID1A mutations. Akin to EECs, EOCs could be stratified into the four molecular subtypes: 3% POLE (ultramutated), 19% MSI (hypermutated), 17% copy-number high (serous-like) and 61% copy-number low (endometrioid). In addition to microsatellite instability, a subset of EOCs harbored potentially targetable mutations, including AKT1 and ERBB2 hotspot mutations. EOCs of MSI (hypermutated) subtype uniformly displayed a good outcome. CONCLUSIONS: EOCs are heterogeneous at the genomic level and harbor targetable genetic alterations. Despite the similarities in the repertoire of somatic mutations between pure EOCs, synchronous EOCs and EECs, the frequencies of mutations affecting known driver genes differ. Further studies are required to define the impact of the molecular subtypes on the outcome and treatment of EOC patients.


Assuntos
Carcinoma Endometrioide/classificação , Carcinoma Epitelial do Ovário/classificação , Neoplasias Ovarianas/classificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patologia , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Cistadenocarcinoma Seroso/classificação , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Análise Mutacional de DNA , Feminino , Humanos , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Intervalo Livre de Progressão , Estudos Retrospectivos
20.
Exp Oncol ; 41(2): 138-143, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31262163

RESUMO

AIM: To analyze copy number variations of HER-2/neu, c-MYC and CCNE1 oncogenes and their protein expression in endometrioid endometrial carcinomas in relation to the degree of tumor progression and presence of a family history of cancer in cancer patients. MATERIALS AND METHODS: The study was conducted on endometrial cancer (EC) samples from 68 patients with I-II FIGO stages of disease. Copy number analysis of HER-2/neu, c-MYC and CCNE1 genes was performed by quantitative PCR. Protein expression was analyzed using immunohistochemistry. RESULTS: Assessment of copy number variations of HER-2/neu, c-MYC and CCNE1 genes revealed their amplification in the tumors of 18.8, 25.0 and 14.3% of EC patients, respectively. High expression of corresponding proteins was detected in 14.6, 23.5 and 65.6% of patients, respectively. It was established that HER-2/neu gene amplification is more common in the group of tumors of low differentiation grade than in moderate grade EC (35.7 and 5.5% of cases, respectively, p < 0.05). Also, high expression of c-Myc protein was more frequently observed in low differentiated tumors compared to the moderately differentiated EC (36.6 and 13.2% of cases, respectively, p < 0.05). Expression of HER-2/neu and cyclin E proteins was found to be dependent on the depth of tumor invasion into the myometrium. High expression of HER-2/neu protein was observed in 25.0 and 4.1% of EC patients with tumor invasion > ½ and < ½ of the myometrium, respectively, and cyclin E - in 86.7 and 46.6% of cases, respectively, p < 0.05. It was shown that among patients with a family history of cancer, a larger proportion of cases with high expression of c-Myc protein was observed compared to the group of patients with sporadic tumors (43.8 and 17.3%, respectively; p < 0.05). CONCLUSIONS: Amplification of HER-2/neu gene, along with high expression of c-Myc, HER-2/neu and cyclin E proteins, are associated with such indices of tumor progression as a low differentiation grade and deep myometrial invasion, suggesting the potential possibility of including these markers in the panel for determining the molecular EC subtype associated with an aggressive course of the disease. In a certain category of EC patients, there is a relationship between a family history of cancer and high expression of c-Myc protein.


Assuntos
Carcinoma Endometrioide/genética , Ciclina E/genética , Neoplasias do Endométrio/genética , Proteínas Oncogênicas/genética , Proteínas Proto-Oncogênicas c-myc/genética , Receptor ErbB-2/genética , Sequência de Bases , Biomarcadores Tumorais/genética , Carcinoma Endometrioide/patologia , Variações do Número de Cópias de DNA/genética , Neoplasias do Endométrio/patologia , Endométrio/patologia , Feminino , Amplificação de Genes/genética , Humanos , Pessoa de Meia-Idade , Miométrio/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA