RESUMO
OBJECTIVE: Breast cancer metastasis to the female genital tract is rare, and the ovaries are the most frequent site of extragenital cancer metastasis. The uterus and cervix have been rarely reported as the site of metastasis. CASE REPORT: A 57-year-old woman diagnosed with invasive lobular carcinoma of the left breast 2 years prior was undergoing tamoxifen treatment. She presented with a right breast mass and postmenopausal bleeding. Synchronous right breast invasive lobular carcinoma with endometrium metastasis was diagnosed. The metastasis tumor involved the endometrium, myometrium, cervix, ovaries, and fallopian tubes. CONCLUSION: We noted the rarity of massive metastasis of the female genital tract from breast cancer. Gynecological surveillance and prompt evaluation of the endometrium led to timely diagnosis and treatment.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Lobular/secundário , Neoplasias do Endométrio/secundário , Neoplasias dos Genitais Femininos/secundário , Carcinoma Lobular/complicações , Neoplasias do Endométrio/complicações , Feminino , Neoplasias dos Genitais Femininos/complicações , Humanos , Pessoa de Meia-Idade , Hemorragia Uterina/etiologiaRESUMO
Melanocytic metastasis to gynecologic organs is rare with most metastases to the ovaries. Metastases to the uterus, or in this case report, a uterine polyp, is exceedingly rare with only 17 cases reported in the literature. Post-menopausal bleeding is the most common presentation of metastatic melanoma in the endometrium, followed by uterine bleeding or abnormal postnatal bleeding in the premenopausal population. We present an 81-year-old woman with metastatic melanoma confined to an endometrial polyp leading to the diagnosis of widespread dissemination of the patient's acral melanoma resected 6 years prior. Although rare, metastatic melanoma should be considered as a cause for abnormal bleeding, especially in the post-menopausal patient with a history of melanoma.
Assuntos
Neoplasias do Endométrio/secundário , Melanoma/secundário , Pólipos/patologia , Neoplasias Cutâneas/patologia , Hemorragia Uterina/etiologia , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/patologia , Endométrio , Feminino , Humanos , Pólipos/complicações , Pós-Menopausa , Melanoma Maligno CutâneoRESUMO
Metastasis of breast cancer to the uterus is quite rare. The majority of reported cases have evolved from previously known invasive ductal and lobular carcinomas of the breast. Herein, a rare case of invasive micropapillary carcinoma of the breast that was diagnosed via endometrial biopsy, without a previous diagnosis or history of breast cancer, was presented. A 58-year-old postmenopausal patient, who had no history of cancer, presented with complaints of abnormal uterine bleeding (AUB) that had begun 2 weeks prior. After undergoing transvaginal ultrasonography, endometrial biopsy, tomography, and positron emission tomography/computed tomography, the patient was preliminarily diagnosed with invasive carcinoma of the breast. The biopsy confirmed the diagnosis of metastatic invasive micropapillary carcinoma of the breast. In postmenopausal AUB, endometrial metastasis of breast cancer should be kept in mind, especially in underdeveloped and developing countries where regular breast cancer screening has not been achieved. KEY WORDS: Breast cancer, Endometrium, Metastasis, Micropapillary carcinoma.
Assuntos
Neoplasias da Mama , Carcinoma Papilar , Neoplasias do Endométrio , Endométrio/patologia , Hemorragia Uterina , Biópsia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/secundário , Neoplasias do Endométrio/secundário , Endométrio/diagnóstico por imagem , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Pós-Menopausa , Hemorragia Uterina/etiologiaRESUMO
AIMS: Microcystic, elongated, and fragmented (MELF) pattern of myoinvasion has been related with increased risk of lympho-vascular space invasion (LVSI) and lymph node metastasis. We analysed a cohort of endometrioid endometrial carcinomas (EECs) to examine the relationships between the MELF pattern of invasion and the clinico-pathological and immunohistochemical features of EEC. METHODS AND RESULTS: 129 EECs were evaluated for the presence of MELF pattern and immunohistochemically tested for Mismatch repair (MMR) proteins, p16, p53 and beta-catenin. We observed 28 MELF + EECs and 101 MELF- EECs. LVSI was observed in 20 MELF + cases and in MELF- tumors. Lymph-node metastases were observed in 7 MELF + cases (2 macrometastases, 3 micrometastases and 2 ITCs). None of the MELF- cases showed micrometastases or ITCs, 18 cases had macrometastatic lymph-nodes. Statistical analysis showed that MELF + tumors carry an increased risk of developing nodal metastasis independent of tumor dimension and LVSI. Loss of MMR proteins expression was observed in 11 MELF + cases and 45 MELF- cases, respectively. Our data showed a higher frequency of immunohistochemical MLH1-PMS2 loss in MELF- pattern of invasion (32.67% of MELF- cases vs 21.43% of MELF + cases) but a higher prevalence of MSH2-MSH6 loss in MELF + pattern (7.14% in MELF + population vs 3.96% of MELF- population) CONCLUSIONS: The morphological recognition of MELF pattern is more reliable than immunohistochemical and molecular signatures of EEC in predicting the risk of nodal involvement. The observed higher prevalence of MSH2-MSH6 loss in MELF + group and MLH1-PMS2 loss in MELF- group may suggest a different molecular signature.
Assuntos
Carcinoma Endometrioide/diagnóstico , Neoplasias do Endométrio/diagnóstico , Linfonodos/patologia , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/secundário , Reparo de Erro de Pareamento de DNA , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/secundário , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Micrometástase de Neoplasia , Estudos RetrospectivosRESUMO
Although many studies have confirmed the relationship between obesity and endometrial cancer (EC), the molecular mechanism between obesity and EC progression has not been elucidated. Overexpression of fat mass and the obesity associated protein FTO leads to weight gain, although recently it has been discovered that FTO can serve as a demethylase which erases N6-methyladenosine (m6A) modification and regulates the metabolization of mRNAs. In this study, we found high expression of FTO in metastatic EC and that this action promote both metastasis and invasion in vivo and in vitro. Mechanistically, FTO can catalyse demethylation modification in 3'UTR region of HOXB13 mRNA, thereby abolishing m6A modification recognition with the YTHDF2 protein. Decreasing HOXB13 mRNA decay and increasing HOXB13 protein expression was accompanied by WNT signalling pathway activation and the expression of downstream proteins, leading to tumour metastasis and invasion. We also found the WNT signalling pathway inhibitor ICG-001 can block HOXB13 gene-induced tumour metastasis, therefore ICG-001 may be a promising molecular intervention. This study provides insight into the relationship between obesity and the pathogenesis of endometrial cancer while highlighting future areas of research.
Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias do Endométrio/secundário , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , RNA Mensageiro/metabolismo , Proteína Wnt1/metabolismo , Adenosina/análogos & derivados , Adenosina/química , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Animais , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Desmetilação , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Feminino , Proteínas de Homeodomínio/genética , Humanos , Camundongos , Camundongos SCID , Invasividade Neoplásica , Prognóstico , Estabilidade de RNA , RNA Mensageiro/química , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Células Tumorais Cultivadas , Proteína Wnt1/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
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 , HumanosRESUMO
BACKGROUND: Systematic retroperitoneal lymphadenectomy has been widely used in the surgical treatment of advanced ovarian cancer patients. Nevertheless, the corresponding therapeutic may not provide a survival benefit. The aim of this study was to assess the effect of systematic retroperitoneal lymphadenectomy in such patients. METHODS: Patients with advanced ovarian cancer (stage III-IV, according to the classification presented by the International Federation of Gynecology and Obstetrics) who were admitted and treated in Zhejiang Cancer Hospital from January 2004 to December 2013 were enrolled and reviewed retrospectively. All patients were optimally or suboptimally debulked (absent or residual tumor < 1 cm) and divided into two groups. Group A (no-lymphadenectomy group, n = 170): patients did not undergo lymph node resection; lymph nodes resection or biopsy were selective. Group B (n = 240): patients underwent systematic retroperitoneal lymphadenectomy. RESULTS: A total of 410 eligible patients were enrolled in the study. The patients' median age was 51 years old (range, 28-72 years old). The 5-year overall survival (OS) and 2-year progression-free survival (PFS) rates were 78 and 24% in the no-lymphadenectomy group and 76 and 26% in the lymphadenectomy group (P = 0.385 and 0.214, respectively). Subsequently, there was no significant difference in 5-year OS and 2-year PFS between the two groups stratified to histological types (serous type or non-serous type), the clinical evaluation of negative lymph nodes or with macroscopic peritoneal metastasis beyond pelvic (IIIB-IV). Multivariate Cox regression analysis indicated that systematic retroperitoneal lymphadenectomy was not a significant factor influencing the patients' survival. Patients in the lymphadenectomy group had a higher incidence of postoperative complications (incidence of infection treated with antibiotics was 21.7% vs. 12.9% [P = 0.027]; incidence of lymph cysts was 20.8% vs. 2.4% [P < 0.001]). CONCLUSIONS: Our study showed that systematic retroperitoneal lymphadenectomy did not significantly improve survival of advanced ovarian cancer patients with residual tumor < 1 cm or absent after cytoreductive surgery, and were associated with a higher incidence of postoperative complications.
Assuntos
Procedimentos Cirúrgicos de Citorredução/mortalidade , Excisão de Linfonodo/mortalidade , Neoplasia Residual/mortalidade , Neoplasias Ovarianas/mortalidade , Neoplasias Peritoneais/mortalidade , Espaço Retroperitoneal/cirurgia , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/secundário , Adenocarcinoma de Células Claras/cirurgia , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/secundário , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/secundário , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/secundário , Neoplasias do Endométrio/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Neoplasia Residual/patologia , Neoplasia Residual/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Prognóstico , Espaço Retroperitoneal/patologia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Recently, sentinel lymph node mapping was introduced in the surgical staging of endometrial cancer as alternative to systematic lymphadenectomy. However, the survival impact of sentinel node mapping is not well characterized yet. METHODS: We performed retrospective study of 104 patients with endometrial cancer treated with sentinel lymph node alone (n = 52) or with pelvic and para-aortic lymphadenectomy (n = 52). For sentinel node mapping, indocyanine green was used. The outcome measure was disease-free survival. RESULTS: Median follow-up was 42 months. Fifty-two patients staged by sentinel lymph node mapping were matched in 1:1 ratio with 52 patients staged by lymphadenectomy using patient age, histological type, tumor stage, tumor grade and lymph and vascular space invasion as matching criteria. The median number of removed lymph node was 3 (range 1-6) and 36 (13-63) in the sentinel and lymphadenectomy group, respectively. The rate of lymph node metastases was not significantly higher in the sentinel group (19.2%) in comparison with the lymphadenectomy group (14.3%). The overall detection rate of sentinel lymph nodes was 100% with a bilateral mapping of 98.1%. Most of the 152 lymph nodes identified and removed were localized in upper paracervical pathway (n = 143, 94.1%). During the follow-up period, overall 21 (20.2%) events were observed, 8 (15.4%) in the sentinel group and 13 (25.0%) in the lymphadenectomy group. The estimated disease-free survival was 84.6% and 75.0% for patients in the sentinel and lymphadenectomy groups, respectively. The survival curves demonstrated similar disease-free survival in two groups (p = 0.774). CONCLUSION: Sentinel lymph node mapping did not compromise the outcome of patients with endometrial cancer.
Assuntos
Neoplasias do Endométrio/secundário , Excisão de Linfonodo/métodos , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: Uterine malignant tumors (uterine cervical carcinoma [UCC], uterine endometrial carcinoma, and uterine sarcoma) are common in women. Brain metastases from uterine malignant tumors are rare, but its incidence has been increasing. The present study aimed to investigate the characteristics of brain metastases from uterine malignant tumors, evaluate predictive factors, and assess the efficacy of Gamma Knife surgery (GKS) for metastases from uterine malignant tumors. METHODS: We retrospectively reviewed the records of patients with brain metastases from uterine malignant tumors treated at Tokyo Gamma Unit Center from 2005 to 2017. RESULTS: We identified 37 patients: 16 had UCC, 12 had uterine endometrial carcinoma, and 9 had uterine sarcoma. Their median age at diagnosis of brain metastases was 54.0 years. The median interval from diagnosis of uterine malignant tumor to brain metastases was 21.0 months, the median number of brain metastases was 3.0, and the median Karnofsky Performance Status at first GKS was 80%. The median survival after first GKS was 6.0 months. All patients had other metastases. Six-month and 1-year survival after first GKS were 48.9% and 32.6%, respectively, and the tumor control rate at 6 months after GKS was 90.8%. Brain metastases from UCC were significantly correlated with good tumor control (P = 0.024). Multivariate analysis determined that Karnofsky Performance Status was significantly associated with patient survival (P = 0.001). CONCLUSIONS: The results of our study suggest that GKS is an acceptable choice for controlling brain metastases from uterine malignant tumors. In particular, GKS provides excellent local control for metastases from UCC.
Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Radiocirurgia/métodos , Neoplasias Uterinas/patologia , Adulto , Idoso , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/secundário , Feminino , Humanos , Estimativa de Kaplan-Meier , Avaliação de Estado de Karnofsky , Pessoa de Meia-Idade , Prognóstico , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Sarcoma/patologia , Sarcoma/secundário , Análise de Sobrevida , Resultado do TratamentoRESUMO
Synchronous primary endometrial and ovarian cancers (SEOs) represent 10% of all endometrial and ovarian cancers and are assumed to develop as independent entities. We investigated the clonal relationship between endometrial and ovarian carcinomas in a large cohort classified as SEOs or metastatic disease (MD). The molecular profiles were compared to The Cancer Genome Atlas (TCGA) data to explore primary origin. Subsequently, the molecular profiles were correlated with clinical outcome. To this extent, a retrospective multicenter study was performed comparing patients with SEOs (n = 50), endometrial cancer with synchronous ovarian metastasis (n = 19) and ovarian cancer with synchronous endometrial metastasis (n = 20). Targeted next-generation sequencing was used, and a clonality index was calculated. Subsequently, cases were classified as POLE mutated, mismatch repair deficient (MMR-D), TP53-wild-type or TP53-mutated. In 92% of SEOs (46/50), the endometrial and concurrent ovarian carcinoma shared at least one somatic mutation, with a clonality index above 0.95, supporting a clonal origin. The SEO molecular profiles showed striking similarities with the TCGA endometrial carcinoma set. SEOs behaved distinctly different from metastatic disease, with a superior outcome compared to endometrial MD cases (p < 0.001) and ovarian MD cases (p < 0.001). Classification according to the TCGA identified four groups with different clinical outcomes. TP53 mutations and extra-utero-ovarian disease were independent predictors for poor clinical outcome. Concluding, SEOs were clonally related in an overwhelming majority of cases and showed a favorable prognosis. Their molecular profile implied a primary endometrial origin. TP53 mutation and extra-utero-ovarian disease were independent predictors for outcome, and may impact adjuvant systemic treatment planning.
Assuntos
Neoplasias do Endométrio/genética , Mutação , Neoplasias Primárias Múltiplas/genética , Neoplasias Ovarianas/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Evolução Clonal , Reparo de Erro de Pareamento de DNA , DNA Polimerase II/genética , Bases de Dados Genéticas , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/secundário , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/secundário , Proteínas de Ligação a Poli-ADP-Ribose/genética , Prognóstico , Estudos Retrospectivos , Proteína Supressora de Tumor p53/metabolismoRESUMO
OBJECTIVES: To compare the diagnostic accuracy of preoperative 18F-FDG PET/CT and MRI tumor markers for prediction of lymph node metastases (LNM) and aggressive disease in endometrial cancer (EC). METHODS: Preoperative whole-body 18F-FDG PET/CT and pelvic MRI were performed in 215 consecutive patients with histologically confirmed EC. PET/CT-based tumor standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and PET-positive lymph nodes (LNs) (SUVmax > 2.5) were analyzed together with the MRI-based tumor volume (VMRI), mean apparent diffusion coefficient (ADCmean), and MRI-positive LN (maximum short-axis diameter ≥ 10 mm). Imaging parameters were explored in relation to surgicopathological stage and tumor grade. Receiver operating characteristic (ROC) curves were generated yielding optimal cutoff values for imaging parameters, and regression analyses were used to assess their diagnostic performance for prediction of LNM and progression-free survival. RESULTS: For prediction of LNM, MTV yielded the largest area under the ROC curve (AUC) (AUC = 0.80), whereas VMRI had lower AUC (AUC = 0.72) (p = 0.03). Furthermore, MTV > 27 ml yielded significantly higher specificity (74%, p < 0.001) and accuracy (75%, p < 0.001) and also higher odds ratio (12.2) for predicting LNM, compared with VMRI > 10 ml (58%, 62%, and 9.7, respectively). MTV > 27 ml also tended to yield higher sensitivity than PET-positive LN (81% vs 50%, p = 0.13). Both VMRI > 10 ml and MTV > 27 ml were significantly associated with reduced progression-free survival. CONCLUSIONS: Tumor markers from 18F-FDG PET/CT outperform MRI markers for the prediction of LNM. MTV > 27 ml yields a high diagnostic performance for predicting aggressive disease and represents a promising supplement to conventional PET/CT reading in EC. KEY POINTS: ⢠Metabolic tumor volume (MTV) outperforms other 18F-FDG PET/CT and MRI markers for preoperative prediction of lymph node metastases (LNM) in endometrial cancer patients. ⢠Using cutoff values for tumor volume for prediction of LNM, MTV > 27 ml yielded higher specificity and accuracy than VMRI> 10 ml. ⢠MTV represents a promising supplement to conventional PET/CT reading for predicting aggressive disease in EC.
Assuntos
Neoplasias do Endométrio/diagnóstico , Fluordesoxiglucose F18/farmacologia , Linfonodos/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/secundário , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Curva ROC , Compostos Radiofarmacêuticos/farmacologiaRESUMO
Previously, based on a DNA microarray experiment, we identified a 96-gene prognostic signature associated with the shorter survival of ovarian cancer patients. We hypothesized that some differentially expressed protein-coding genes from this signature could potentially serve as prognostic markers. The present study was aimed to validate two proteins, namely fibronectin (FN1) and periostin (POSTN), in the independent set of ovarian cancer samples. Both proteins are mainly known as extracellular matrix proteins with many important functions in physiology. However, there are also indications that they are implicated in cancer, including ovarian cancer. The expression of these proteins was immunohistochemically analyzed in 108 surgical samples of advanced ovarian cancer (majority: high-grade serous) and additionally on tissue arrays representing different stages of the progression of ovarian and fallopian tube epithelial tumors, from normal epithelia, through benign tumors, to adenocarcinomas of different stages. The correlation with clinical, pathological, and molecular features was evaluated. Kaplan-Meier survival analysis and Cox-proportional hazards models were used to estimate the correlation of the expression levels these proteins with survival. We observed that the higher expression of fibronectin in the tumor stroma was highly associated with shorter overall survival (OS) (Kaplan-Meier analysis, log-rank test p = 0.003). Periostin was also associated with shorter OS (p = 0.04). When we analyzed the combined score, calculated by adding together individual scores for stromal fibronectin and periostin expression, Cox regression demonstrated that this joint FN1&POSTN score was an independent prognostic factor for OS (HR = 2.16; 95% CI: 1.02-4.60; p = 0.044). The expression of fibronectin and periostin was also associated with the source of ovarian tumor sample: metastases showed higher expression of these proteins than primary tumor samples (χ2 test, p = 0.024 and p = 0.032). Elevated expression of fibronectin and periostin was also more common in fallopian cancers than in ovarian cancers. Our results support some previous observations that fibronectin and periostin have a prognostic significance in ovarian cancer. In addition, we propose the joint FN1&POSTN score as an independent prognostic factor for OS. Based on our results, it may also be speculated that these proteins are related to tumor progression and/or may indicate fallopian-epithelial origin of the tumor.
Assuntos
Adenocarcinoma Mucinoso/secundário , Biomarcadores Tumorais/metabolismo , Moléculas de Adesão Celular/metabolismo , Cistadenocarcinoma Seroso/secundário , Neoplasias do Endométrio/secundário , Fibronectinas/metabolismo , Neoplasias Ovarianas/patologia , Adenocarcinoma Mucinoso/tratamento farmacológico , Adenocarcinoma Mucinoso/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/metabolismo , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/metabolismo , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was induced in hypoxia and participated in cancer development. However, the role of PLOD2 in endometrial carcinoma remains unclear. OBJECTIVE: To explore the influences and regulation mechanism of PLOD2 in endometrial carcinoma under hypoxic condition. METHODS: The small interfering RNA (siRNA) targeting to PLOD2 and pcDNA3.1-PLPD2 were transfected to endometrial carcinoma cells to alter PLOD2 expression. Cell proliferation ability was determined by colony formation assay. Wound healing assay used to detect cell migration ability. Transwell invasion assay was used to detect cell invasion ability. RESULTS: PLOD2 and Hypoxia-inducible factor-1α (HIF-1α) were induced by hypoxia. Down-regulation of PLOD2 did not affect endometrial carcinoma cell proliferation ability, while inhibited cell migration, invasion under hypoxic condition. Besides, down-regulation of PLOD2 increased the levels of γ-catenin and E-cadherin and decreased levels of Fibronectin and Snail under hypoxic condition. Down-regulation of PLOD2 also inactivated Src and phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) signaling under hypoxic condition. The promoting effects of PLOD2 overexpression on migration, invasion and epithelial-mesenchymal transition (EMT) of endometrial carcinoma cells were reversed by Akt inhibitor (MK2206) under hypoxic condition. CONCLUSION: PLOD2 expression was increased in endometrial carcinoma cells under hypoxic condition. PLOD2 modulated migration, invasion, and EMT of endometrial carcinoma cells via PI3K/Akt signaling. PLOD2 may be a potential therapeutic target for endometrial carcinoma.
Assuntos
Movimento Celular/genética , Neoplasias do Endométrio/metabolismo , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo , Caderinas/metabolismo , Hipóxia Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Neoplasias do Endométrio/enzimologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/secundário , Feminino , Fibronectinas/metabolismo , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/genética , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno , Transdução de Sinais/genética , Fatores de Transcrição da Família Snail/metabolismo , gama Catenina/metabolismo , Quinases da Família src/metabolismoRESUMO
AIMS: Testis Expressed 19 (TEX19) is one of cancer/testis antigens identified in recent years and is related to the oncogenesis and progress of several cancers. This study aimed to reveal the role of TEX19 in ovarian cancer (OC) and searched for potential candidate epitope peptides of TEX19 to facilitate clinical application. MAIN METHODS: TEX19 levels were evaluated by immunohistochemistry (IHC) in 98 human ovarian tissue samples. The correlation of TEX19 levels with patients' clinicopathological features was assessed. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were utilized to detect TEX19 levels in ovarian cell lines and TEX19-deficient cells. The level of TEX19 in OVCAR-3 and A2780 was knocked down by small interfering RNA (siRNA), and loss-of-function assays were used to determine the biological effects of TEX19 on the proliferation, migration, and invasion of OC cells. Subsequently, candidate epitope peptides from TEX19 were predicted and verified by the IEDB database, pepsite2 website, MOE software, and T2 cell binding assay. KEY FINDINGS: TEX19 was significantly upregulated in OC which correlated to higher TNM stage, lymph node involvement, and invasiveness. Knockdown of TEX19 inhibited proliferation, migration, and invasion of OC cells. Additionally, we screened four peptides derived from TEX19 and found TL to be the dominant peptide with the greatest affinity with HLA-A*0201. SIGNIFICANCE: Our data indicated a cancer-promoting effect of TEX19 in OC and demonstrated that TL could be a potential candidate for an anti-tumor epitope vaccine of OC, suggesting that TEX19 is a promising biomarker and immunotherapeutic target for OC.
Assuntos
Adenocarcinoma de Células Claras/secundário , Adenocarcinoma Mucinoso/secundário , Cistadenocarcinoma Seroso/secundário , Neoplasias do Endométrio/secundário , Epitopos/imunologia , Neoplasias Ovarianas/patologia , Proteínas de Ligação a RNA/imunologia , Proteínas de Ligação a RNA/metabolismo , Adenocarcinoma de Células Claras/imunologia , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma Mucinoso/imunologia , Adenocarcinoma Mucinoso/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Proliferação de Células , Cistadenocarcinoma Seroso/imunologia , Cistadenocarcinoma Seroso/metabolismo , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/metabolismo , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/metabolismo , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Adulto JovemRESUMO
In 2018, around 382,100 new cases of endometrial cancer (EC) were reported worldwide, accounting for about 4.4% of all new cases of cancer in women. In France, in 2018, the EC is the first gynecological cancer in incidence and the fourth cancer in women. The rationale for the therapeutic management of EC is based on the estimation of a theoretical risk of recurrence and lymph node metastasis using MRI and preoperative biopsy criteria. However, lymph node status remains the determining factor of adjuvant treatment. In order to reduce the morbidity of lymphadenectomy, the concept of sentinel lymph node biopsy (SLN) has been developed. The SLN technique has evolved in recent years, thanks to the advent of robotics and the creation of fluorescence detection cameras. It has been shown that detection of SLN with Indocyanine Green (ICG) allows for more frequent bilateral migration of 88 to 100% and better detection of pelvic GS in 97% of cases with a decrease in morbidity. Recently, in view of the absence of a therapeutic role of lymph node staging, the operational risks and the delay of adjuvant treatments, in case of pelvic lymph node metastasis on definitive histological examination, the question of secondarily performing paraaortic lymphadenectomy arises. The SLN procedure, extended to all early-stage endometrial cancers, should lead to a major reduction in the use of secondary staging and better adaptation of adjuvant therapy.
Assuntos
Neoplasias do Endométrio/secundário , Neoplasias do Endométrio/terapia , Metástase Linfática/patologia , Biópsia de Linfonodo Sentinela , Feminino , Humanos , Excisão de LinfonodoRESUMO
OBJECTIVE: To evaluate the clinical and pathological features of endometrial cancer (EC) following breast cancer and to assess the effect of the breast cancer hormone receptor status on subsequent EC. MATERIALS: A retrospective study based on SEER data of EC patients with a history of breast cancer. RESULTS: A total of 2142 cases met the inclusion criteria. Compared to that of the general population, the incidence of EC following estrogen receptor-positive (ER+) breast cancer and hormone receptor-negative (HR-) breast cancer increased by approximately 16-fold and 15-fold, respectively. Histologically, the proportions of type II EC following ER+ breast cancer, HR- breast cancer and primary EC were 39.6%, 39.4% and 31.2%, respectively (P < 0.001). The proportions of G3 ECs were 26.9%, 28.2% and 19.8%, respectively (P < 0.001). The proportion of patients who died from miscellaneous malignant tumors among EC patients following breast cancer was significantly higher than the proportion of patients among primary ECs. The overall survival rate was worse for EC patients with a history of breast cancer (P < 0.001). There were no significant differences between patients with EC following ER+ breast cancer and those with EC following HR- breast cancer with regard to stage, lymphatic metastasis, outcome or cause of death. CONCLUSIONS: Compared to the general population, the incidence of EC in patients with breast cancer was increased markedly. Patients with EC following ER+ or HR- breast cancer shared the same clinicopathological features and prognoses. All patients need close monitoring regardless of breast cancer hormone receptor status.
Assuntos
Neoplasias da Mama/complicações , Neoplasias do Endométrio/secundário , Idoso , Neoplasias da Mama/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
RATIONALE: High-stage endometrial carcinoma is an aggressive tumor with a high propensity for distant spread. However, metastases to the pericardium are rare in gynecological cancer, and are usually fatal. PATIENT CONCERNS: A 69-year-old woman was diagnosed with endometrial carcinoma with pericardium metastasis. The symptoms at presentation were panic and shortness of breath. DIAGNOSES: The cytologic examination of pericardial fluid obtained by pericardiocentesis confirmed metastasis. INTERVENTIONS: In addition to cisplatin instilled into the pericardial space, for systemic chemotherapy, we chose that gemcitabine and lobaplatin regimen be preferred. OUTCOMES: The patient has been participating in telephone follow-up for 8 months and has generally remained in a good condition. LESSONS: Endometrial carcinoma can have pericardial metastases. When this happens, we recommend ultrasound-guided pericardial puncture and the pericardial injection of cisplatin, in combination with systemic chemotherapy that consists of gemcitabine and lobaplatin.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Endométrio/secundário , Neoplasias Cardíacas/complicações , Derrame Pericárdico/etiologia , Pericardiocentese/métodos , Idoso , Terapia Combinada , Diagnóstico Diferencial , Ecocardiografia , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/terapia , Feminino , Neoplasias Cardíacas/secundário , Neoplasias Cardíacas/terapia , Humanos , Imageamento por Ressonância Magnética , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/terapia , Pericárdio , Tomografia Computadorizada por Raios XAssuntos
Neoplasias do Endométrio/secundário , Melanoma/patologia , Neoplasias Cutâneas/patologia , Hemorragia Uterina/etiologia , Idoso , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Imuno-Histoquímica , Excisão de Linfonodo , Pós-Menopausa , Salpingo-Ooforectomia , Melanoma Maligno CutâneoRESUMO
BACKGROUND: Hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP) has shown to be overexpressed in several human cancers. The purpose of this study was to explore the expression of HPIP in endometrial cancer (EC) and its associated effects on disease. METHODS: A total of 113 EC patients at the Harbin Medical University Cancer Hospital between August 2011 and September 2012 were studied for immunohistochemistry analysis. HPIP expression was detected using real-time reverse transcription PCR, Western blotting, and immunohistochemistry. Prognostic value of HPIP expression was examined using multivariate Cox regression analysis and Kaplan-Meier method. RESULTS: The result of Western blotting indicated that HPIP protein expression is significantly high in normal tissues compared to EC tissues (P < 0.001). The expression of HPIP was significantly associated with FIGO stage (P < 0.001), histological grade (P < 0.001), depth of myometrial invasion (P < 0.001), and lymph node metastasis (P = 0.033). Kaplan-Meier analysis demonstrated that there was a significant difference in overall survival and disease-free survival between the two groups of patients stratified by HPIP expression level (log-rank, both P = 0.002). Patients with HPIP high expression had significantly shorter median survival time than those with HPIP low expression. Moreover, results of the multivariate analysis revealed that HPIP expression was an independent prognostic factor for predicting overall survival (P = 0.015) and disease-free survival (P = 0.017) in patients with EC. CONCLUSION: The present study provides evidence that HPIP predicts EC progression and poor survival, highlighting its potential as a therapeutic target for EC.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias do Endométrio/secundário , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/cirurgia , Feminino , Seguimentos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Taxa de SobrevidaRESUMO
A 44-year female was admitted to the hospital, complaining of vaginal bleeding. Ultrasound imaging revealed two masses in the pelvic cavity, measuring 6.6 x 3.4 x 1.8 cm and 8.2 x 4.7 x 3.7 cm in size. After surgical debulking of the tumours, the patient underwent abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic disease dissection, appendicectomy, omentectomy, and pelvic lymph node dissection. Histological and immunochemical examinations confirmed the diagnosis of serous carcinomas in both ovaries involving the right tubal fimbria, the omentum, pelvic nodules, and the endometrium. Ovarian serous carcinoma spreading to the endometrium is a rare phenomenon and may mimick a primary uterine serous cercinoma. Although difficult, it is important to distinguish concomitant independent primary tumours from metastases because the most appropriate management strategy and prognosis differs in both.