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Chinese Journal of Obstetrics and Gynecology ; (12): 733-741, 2023.
Article in Chinese | WPRIM | ID: wpr-1012282


Objective: To investigate the relationships between molecular types of the cancer genome atlas (TCGA) of patients with endometrial carcinoma (EC) and lymph node metastasis and other clinicopathological features. Methods: The clinical pathological information of 295 patients with EC who underwent initial inpatient surgical treatment and accepted the detection of the molecular types of TCGA with next-generation sequencing technology at Peking University People's Hospital were collected during April 2016 and May 2022. The TCGA molecular typing of EC was divided into four types: POLE-ultramutated (15 cases), high microsatellite instability (MSI-H; 50 cases), copy-number low (CNL; 175 cases), and copy-number high (CNH; 55 cases). The differences of clinical pathological features among different molecular types and the risk factors of lymph node metastasis were analyzed retrospectively. Results: Among 295 patients with EC, the average age was (56.9±0.6) years. (1) There was a statistically significant difference in lymph node metastasis (0, 8.0%, 10.3% and 25.5%) among the four molecular types (χ2=12.524, P=0.006). There were significant differences in age, stage, pathological type, grade (only endometrioid carcinoma), myometrium invasion, lymphatic vascular space infiltration, and estrogen receptor among the EC patients of four molecular types (all P<0.05). Among them, while in the patients with CNH type, the pathological grade was G3, the pathological type was non-endometrioid carcinoma, and the proportion of myographic infiltration depth ≥1/2 were higher (all P<0.05). (2) Univariate analysis suggested that pathological type, grade, myometrium infiltration depth, cervical interstitial infiltration, lymphatic vascular space infiltration, and progesterone receptor were all factors which significantly influence lymph node metastasis (all P<0.01); multivariate analysis suggested that the lymphatic vascular space infiltration was an independent risk factor for lymph node metastasis (OR=5.884, 95%CI: 1.633-21.211; P=0.007). (3) The factors related to lymph node metastasis were different in patients with different molecular types. In the patients with MSI-H, the non-endometrioid carcinoma of pathological type was independent risk factor for lymph node metastasis (OR=29.010, 95%CI: 2.067-407.173; P=0.012). In the patients with CNL, myometrium infiltration depth≥1/2 (OR=4.995, 95%CI: 1.225-20.376; P=0.025), lymphatic vascular space infiltration (OR=14.577, 95%CI: 3.603-58.968; P<0.001) were the independent risk factors for lymph node metastasis. While in the CNH type patients pathological type of non-endometrioid carcinoma (OR=7.451, 95%CI: 1.127-49.281; P=0.037), cervical interstitial infiltration (OR=22.938, 95%CI: 1.207-436.012; P=0.037), lymphatic vascular space infiltration (OR=9.404, 95%CI: 1.609-54.969; P=0.013), were the independent risk factors for lymph node metastasis. Conclusions: POLE-ultramutated EC patients have the lowest risk of lymph node metastasis, and CNH patients have the highest risk of lymph node metastasis. The risk factors of lymph node metastasis of different molecular types are different. According to preoperative pathological and imaging data, lymph node metastasis is more likely to occur in patients with non-endometrioid carcinoma in MSI-H and CNH type patients, and lymph node metastasis is more likely to occur in patients with myometrium infiltration depth ≥1/2 in CNL type patients.

Female , Humans , Middle Aged , Carcinoma, Endometrioid/pathology , Endometrial Neoplasms/pathology , Lymph Node Excision , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Neoplasm Staging , Retrospective Studies , Risk Factors , Risk Assessment , Molecular Typing
Chinese Medical Journal ; (24): 2609-2620, 2023.
Article in English | WPRIM | ID: wpr-1007546


BACKGROUND@#Observational research has reported that systemic lupus erythematosus (SLE) is related to common female hormone-dependent cancers, but the underlying causal effect remains undefined. This study aimed to explore the causal association of these conditions by Mendelian randomization (MR) analysis.@*METHODS@#We selected instrumental variables for SLE from genome-wide association studies (GWASs) conducted in European and East Asian populations. The genetic variants for female malignant neoplasms were obtained from corresponding ancestry GWASs. We utilized inverse variance weighted (IVW) as the primary analysis, followed by sensitivity analysis. Furthermore, we conducted multivariable MR (MVMR) to estimate direct effects by adjusting for the body mass index and estradiol. Finally, we implemented reverse direction MR analysis and gave a negative example to test the reliability of MR results.@*RESULTS@#We found SLE was significantly negatively associated with overall endometrial cancer risk (odds ratio [OR] = 0.961, 95% confidence interval [CI] = 0.935-0.987, P  = 3.57E-03) and moderately inversely related to endometrioid endometrial cancer (ENEC) (OR = 0.965, 95% CI = 0.936-0.995, P  = 0.024) risk in the European population by IVW. We replicated these results using other MR models and detected a direct effect by MVMR (overall endometrial cancer, OR = 0.962, 95% CI = 0.941-0.983, P  = 5.11E-04; ENEC, OR = 0.964, 95% CI = 0.940-0.989, P  = 0.005). Moreover, we revealed that SLE was correlated with decreased breast cancer risk (OR = 0.951, 95% CI = 0.918-0.986, P  = 0.006) in the East Asian population by IVW, and the effect was still significant in MVMR (OR = 0.934, 95% CI = 0.859-0.976, P  = 0.002). The statistical powers of positive MR results were all >0.9.@*CONCLUSION@#This finding suggests a possible causal effect of SLE on the risk of overall endometrial cancer and breast cancer in European and East Asian populations, respectively, by MR analysis, which compensates for inherent limitations of observational research.

Female , Humans , Genome-Wide Association Study , Mendelian Randomization Analysis , Neoplasms, Hormone-Dependent , Reproducibility of Results , Endometrial Neoplasms , Lupus Erythematosus, Systemic/genetics , Carcinoma, Endometrioid , Breast Neoplasms , Polymorphism, Single Nucleotide
Journal of Central South University(Medical Sciences) ; (12): 941-946, 2023.
Article in English | WPRIM | ID: wpr-982367


Primary endometrioid adenocarcinoma of the rectovaginal septum is rare. Its pathogenesis is not clear and there is no standard treatment. One patient with endometrioid adenocarcinoma of the rectovaginal septum arising from deep infiltrative endometriosis was admitted to Qingdao Municipal Hospital. The patient presented with incessant menstruation and abdominal distension. She had bilateral ovarian endometriotic cystectomy 6 years ago. Imaging findings suggested a pelvic mass which might invade the rectovaginal septum. Pathological results of primary surgery confirmed endometrioid carcinoma of the pelvic mass arising from the rectovaginal septum. Then she had a comprehensive staged surgery. Postoperative chemotherapy was given 6 times. No recurrence or metastasis was found during the 2-year follow-up. The possibility of deep infiltrating endometriosis and its malignant transformation should be considered in the differential diagnosis of a new extragonadal pelvic lesion in a patient with a history of endometriosis, which would avoid misdiagnosis and missed diagnosis.

Female , Humans , Carcinoma, Endometrioid/surgery , Endometriosis/surgery , Rectum , Vagina , Cystectomy
Journal of Peking University(Health Sciences) ; (6): 370-374, 2023.
Article in Chinese | WPRIM | ID: wpr-986864


Independent primary uterine and cervical adenocarcinoma are rare and difficult to identify their origins, which makes treatment decision difficult. A 46-year-old female with endometrioid carcinoma and adenocarcinoma, human papilloma virus (HPV)-associated of the uterine cervix was reported. The patient presented with increased menstrual flow, contact bleeding and watery leucorrhea for more than one year, and the imaging findings showed abnormal uterine morphology, irregular margins, and multiple abnormal signals in uterine cavity and myometrium, which suggested multiple leiomyomas of the uterus. The signal intensity in the right muscle layer was markedly enhanced, suggesting a smooth muscle tumor of uncertain malignant potential. A large number of cystic hypointensity was seen in the cervix, and multiple cysts were considered. The initial preoperative diagnosis was multiple leiomyoma of the uterus, and a hysterectomy operation was planned. During the operation, the uterus was sent for frozen sections. There was a mass in the endometrium of the fundus, with a soft grayish-red cut surface and a clear border with the myometrium, and there was a grayish-white nodule in the cervix with a hard grayish-white cut surface. The two masses were well demarcated from each other, and the distance between them was 30 mm. The result of the frozen sections indicated the malignant tumor of the endometrium, and the extended hysterectomy+pelvic lymphadenectomy+partial resection of the greater omentum was performed. After the operation, the paraffin sections were sent to the Department of Pathology of the Peking University Third Hospital for histochemistry, POLE gene sequencing and HPV RNAscope tests, and the final diagnosis was a synchronous endometrioid carcinoma (POLE-mutant according to the WHO classification) and an adenocarcinoma, HPV-associated of the uterine cervix. Now the patient had been treated with 2 cycles of chemotherapy and her condition was fine. Through the analysis of the histological, immunohistochemical and molecular detection results of this case, the importance of applying HPV RNAscope and TCGA molecular typing in the diagnosis of cervical adenocarcinomas and endometrial carcinomas was emphasized. At the same time, gynecologists should not blindly rely on intraoperative frozen sections, and should pay attention to preoperative pathological examination, and make appropriate operation methods according to the results in order to prevent passivity in the surgery.

Humans , Female , Middle Aged , Carcinoma, Endometrioid/pathology , Uterine Cervical Neoplasms/pathology , Papillomaviridae , Papillomavirus Infections/pathology , Uterus/pathology , Adenocarcinoma/diagnosis
Journal of Peking University(Health Sciences) ; (6): 366-369, 2023.
Article in Chinese | WPRIM | ID: wpr-986863


Corded and hyalinized endometrioid carcinoma (CHEC) is a morphologic variant of endo-metrioid adenocarcinoma. The tumor exhibits a biphasic appearance with areas of traditional low-grade adenocarcinoma merging directly with areas of diffuse growth composed of epithelioid or spindled tumor cells forming cords, small clusters, or dispersed single cells. It is crucial to distinguish CHEC from its morphological mimics, such as malignant mixed mullerian tumor (MMMT), because CHECs are usually low stage, and are associated with a good post-hysterectomy prognosis in most cases while the latter portends a poor prognosis. The patient reported in this article was a 54-year-old woman who presented with postmenopausal vaginal bleeding for 2 months. The ultrasound image showed a thickened uneven echo endometrium of approximately 12.2 mm and a detectable blood flow signal. Magnetic resonance imaging revealed an abnormal endometrial signal, considered endometrial carcinoma (Stage Ⅰ B). On hysterectomy specimen, there was an exophytic mass in the uterine cavity with myometrium infiltrating. Microscopically, most component of the tumor was well to moderately differentiated endometrioid carcinoma. Some oval and spindle stromal cells proliferated on the superficial surface of the tumor with a bundle or sheet like growth pattern. In the endometrial curettage specimen, the proliferation of these stromal cells was more obvious, and some of the surrounding stroma was hyalinized and chondromyxoid, which made the stromal cells form a cord-like arrangement. Immunostains were done and both the endometrioid carcinoma and the proliferating stroma cells showed loss of expression of DNA mismatch repair protein MLH1/PMS2 and wild-type p53 protein. Molecular testing demonstrated that this patient had a microsatellite unstable (MSI) endometrial carcinoma. The patient was followed up for 6 months, and there was no recurrence. We diagnosed this case as CHEC, a variant of endometrioid carcinoma, although this case did not show specific β-catenin nuclear expression that was reported in previous researches. The striking low-grade biphasic appearance without TP53 mutation confirmed by immunohistochemistry and molecular testing supported the diagnosis of CHEC. This special morphology, which is usually distributed in the superficial part of the tumor, may result in differences between curettage and surgical specimens. Recent studies have documented an aggressive clinical course in a significant proportion of cases. More cases are needed to establish the clinical behaviors, pathologic features, and molecular profiles of CHECs. Recognition of the relevant characteristics is the prerequisite for pathologists to make correct diagnoses and acquire comprehensive interpretation.

Female , Humans , Middle Aged , Carcinoma, Endometrioid/surgery , Endometrial Neoplasms/pathology , Endometrium/metabolism , Adenocarcinoma/pathology , Stromal Cells/pathology
Rev. bras. ginecol. obstet ; 43(2): 137-144, Feb. 2021. tab, graf
Article in English | LILACS | ID: biblio-1156096


Abstract Objective The present study aims to evaluate the profile of endometrial carcinomas and uterine sarcomas attended in a Brazilian cancer center in the period from 2001 to 2016 and to analyze the impact of time elapsed fromsymptoms to diagnoses or treatment in cancer stage and survival. Methods This observational study with 1,190 cases evaluated the year of diagnosis, age-group, cancer stage and histological type. A subgroup of 185 women with endometrioid histology attended in the period from 2012 to 2017 was selected to assess information about initial symptoms, diagnosticmethods, overall survival, and to evaluate the influence of the time elapsed from symptoms to diagnosis and treatment on staging and survival. The statistics used were descriptive, trend test, and the Kaplan- Meier method, with p-values < 0.05 for significance. Results A total of 1,068 (89.7%) carcinomas (77.2% endometrioid and 22.8% nonendometrioid) and 122 (10.3%) sarcomas were analyzed, with an increasing trend in the period (p < 0.05). Histologies of non-endometrioid carcinomas, G3 endometrioid, and carcinosarcomas constituted 30% of the cases. Non-endometrioid carcinomas and sarcomas weremore frequently diagnosed in patients over 70 years of age and those on stage IV (p < 0.05). The endometrioid subgroup with 185 women reported 92% of abnormal uterine bleeding and 43% diagnosis after curettage. The average time elapsed between symptoms to diagnosis was 244 days, and between symptoms to treatment was 376 days, all without association with staging (p = 0.976) and survival (p = 0.160). Only 12% of the patients started treatment up to 60 days after diagnosis. Conclusion The number of uterine carcinoma and sarcoma cases increased over the period of 2001 to 2016. Aggressive histology comprised 30% of the patients and, for endometrioid carcinomas, the time elapsed between symptoms and diagnosis or treatment was long, although without association with staging or survival.

Resumo Objetivo O presente estudo avaliou o perfil dos carcinomas endometriais e sarcomas uterinos atendidos em um centro brasileiro de câncer no período de 2001 a 2016, e avaliou o impacto do tempo decorrido entre os sintomas até o diagnóstico ou tratamento no estadiamento e sobrevida pelo câncer. Métodos Estudo observacional com 1.190 casos que analisou o ano do diagnóstico, faixa etária, estágio e tipo histológico do câncer. Um subgrupo de 185 mulheres com histologia endometrioide e atendidas no período de 2012 a 2017 foi selecionado para avaliar informações sobre sintomas iniciais, métodos de diagnóstico, sobrevida global e para analisar a relação entre o tempo decorrido a partir dos sintomas até o diagnóstico e tratamento no estadiamento e sobrevida. Foram realizadas análises estatísticas descritiva, de tendência linear e de sobrevida pelo método de Kaplan-Meier, com valores de p < 0,05 para significância. Resultados Os casos estudados de acordo com a histologia foram 1.068 (89,7%) carcinomas (77,2% endometrioides e 22,8% não endometrioides) e 122 (10,3%) sarcomas, com tendência crescente no período (p < 0,05). Histologias de carcinomas não endometrioides, G3 endometrioides e carcinossarcomas consistiram em 30% dos casos. Carcinomas não endometrioides e sarcomas forammais frequentemente diagnosticados em pacientes acima de 70 anos de idade e em estágio IV (p < 0,05). O subgrupo com185 mulheres com carcinoma endometrioide apresentou 92% de sangramento uterino anormal e 43% de diagnóstico após curetagem. O tempo médio decorrido entre os sintomas e o diagnóstico foi de 244 dias e entre os sintomas e o tratamento, 376 dias, todos sem associação com estadiamento (p = 0,976) e sobrevida (p = 0,160). Apenas 12% das pacientes iniciaram o tratamento em até 60 dias após o diagnóstico. Conclusão O número de casos de carcinomas e sarcomas uterinos aumentaram no período de 2001 a 2016. A histologia agressiva compreendeu 30% dos pacientes e, no caso dos carcinomas endometrioides, o tempo decorrido entre os sintomas e o diagnóstico ou tratamento foi longo, embora sem associação com estadiamento ou sobrevida.

Humans , Female , Aged , Sarcoma/diagnosis , Uterine Neoplasms/diagnosis , Carcinoma, Endometrioid/diagnosis , Sarcoma/surgery , Sarcoma/pathology , Time Factors , Uterine Neoplasms/surgery , Uterine Neoplasms/pathology , Brazil/epidemiology , Retrospective Studies , Risk Factors , Age Factors , Carcinoma, Endometrioid/surgery , Carcinoma, Endometrioid/pathology , Middle Aged , Neoplasm Staging
Rev. bras. ginecol. obstet ; 43(1): 35-40, Jan. 2021. tab
Article in English | LILACS | ID: biblio-1156073


Abstract Objective To evaluate the presence of residual disease in the uterine specimen after hysteroscopic polypectomy or polyp biopsy in patients with endometrioid endometrial cancer (EC). Methods We analyzed a series of 104 patients (92 cases from the Hospital AC Camargo and 12 from the Hospital do Servidor Público Estadual de São Paulo) with polyps that were diagnosed by hysteroscopy, showing endometrioid EC associated with the polyp or in the final pathological specimen. Patients underwent a surgical approach for endometrial cancer from January 2002 to January 2017. Their clinical and pathological data were retrospectively retrieved from the medical records. Results In78cases (75%), thepolyphad EC, and in 40(38.5%), itwas restricted tothe polyp, without endometrial involvement. The pathologic stage was IA in 96 cases (92.3%) and 90 (86.5%) had histologic grade 1 or 2. In 18 cases (17.3%), there was no residual disease in the final uterine specimen, but only in 9 of them the hysteroscopy suggested that the tumor was restricted to the polyp. In 5 cases (4.8%) from the group without outside of the polyp during hysteroscopy, myometrial invasion was noted in the final uterine specimen. This finding suggests the possibility of disease extrapolation through the base of the polyp. Conclusion Patients with endometrioid EC associated with polyps may have the tumor completely removed during hysteroscopy, but the variables shown in the present study could not safely predict which patient would have no residual disease.

Resumo Objetivo Avaliar a presença de doença residual no exame anatomopatológico definitivo de pacientes com câncer de endométrio endometrioide após polipectomia ou biópsia de pólipo histeroscópica. Métodos Analisamos 104 pacientes (92 casos do Hospital AC Camargo e 12 casos do Hospital do Servidor Público Estadual de São Paulo) com pólipos diagnosticados durante histeroscopia e cuja biópsia histeroscópica ou exame patológico final do útero acusaram câncer de endométrio endometrioide. As pacientes foram submetidas a cirurgia para câncer de endométrio de janeiro de 2002 a janeiro de 2017. Os dados clínicos e anatomopatológicos de cada paciente foram retirados dos prontuários médicos Resultados Em 78 casos (75%), o pólipo continha a neoplasia, e em 40 (38.5%), ela estava restrita ao tecido do pólipo, sem envolvimento endometrial adjacente. O estadio final foi IA em 96 casos (92.3%) e em 90 (86.5%) tratava-se de grau 1 ou 2. Em 18 casos (17.3%), não havia doença residual no espécime uterino, mas emapenas 9 deles a histeroscopia sugeriu doença restrita ao pólipo. Em 5 casos (4.8%), não havia doença aparente extrapólipo na histeroscopia, mas havia invasão miometrial, sugerindo extravasamento do tumor pela base do pólipo. Conclusão Pacientes com câncer de endométrio associado a pólipos podem ter o tumor completamente removido durante a histeroscopia, mas, com as variáveis avaliadas, é difícil predizer com segurança qual paciente ficará sem tumor residual.

Humans , Female , Polyps/surgery , Endometrial Neoplasms/surgery , Carcinoma, Endometrioid/surgery , Neoplasm, Residual/surgery , Neoplasm Recurrence, Local/surgery , Polyps/pathology , Hysteroscopy , Endometrial Neoplasms/pathology , Carcinoma, Endometrioid/pathology , Neoplasm, Residual/pathology , Middle Aged , Neoplasm Recurrence, Local/pathology
Rev. bras. ginecol. obstet ; 43(1): 41-45, Jan. 2021. tab
Article in English | LILACS | ID: biblio-1156074


Abstract Objective The aim of the present study was to analyze relapse rates and patterns in patients with endometrial cancer with the aim of evaluating the effectiveness of current follow-up procedures in terms of patient survival, as well as the convenience of modifying the surveillance strategy. Methods Retrospective descriptive study including all patients diagnosed with endometrial cancer relapse at the Department of Gynecology and Obstetrics of the Complejo Hospitalario Insular-Materno Infantil de Canarias, between 2005 and 2014. Results Recurrence was observed in 81 patients (10.04% of the sample); 66.7% of them suffered relapse within 2 years and 80.2% within 3 years after the termination of the primary treatment; 41.9% showed distant metastases while the rest corresponded to local-regional (40.7%) or ganglionar (17.4%) relapse; 42% of these were symptomatic; 14 patients showed more than 1 site of relapse. Relapse was detected mainly through symptoms and physical examination findings (54.3%), followed by elevated serummarker levels (29.6%), computed tomography (CT) images (9.9%) and abnormal vaginal cytology findings (6.2%). No differences in global survival were found between patients with symptomatic or asymptomatic relapse. Conclusion Taking into account that the recurrence rate of endometrial cancer is low, that relapse occurs mainly within the first 3 years post-treatment and that symptom evaluation and physical examination are the most effective follow-up methods, we postulate that a modification of the current model of hospital follow-up should be considered.

Humans , Female , Clinical Protocols/standards , Endometrial Neoplasms/mortality , Carcinoma, Endometrioid/mortality , Neoplasm Recurrence, Local/mortality , Spain , Women's Health Services , Tomography, X-Ray Computed , Retrospective Studies , Outcome Assessment, Health Care , Endometrial Neoplasms/surgery , Endometrial Neoplasms/pathology , Endometrial Neoplasms/diagnostic imaging , Carcinoma, Endometrioid/surgery , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/diagnostic imaging , Disease-Free Survival , Middle Aged , Neoplasm Recurrence, Local/surgery , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Staging
Rev. méd. Minas Gerais ; 31: 31416, 2021.
Article in Portuguese | LILACS | ID: biblio-1354551


O presente relato de caso descreve a apresentação atípica de uma paciente com adenocarcinoma endometrioide invasivo que evoluiu com aplasia pura adquirida crônica da série vermelha secundária à quimioterapia. Paciente de 71 anos, sexo feminino, procurou atendimento médico por quadro de metrorragia com três meses de evolução. A curetagem uterina evidenciou adenocarcinoma endometrioide invasor moderadamente diferenciado. Iniciou-se uma abordagem com esquema quimioterápico composto por Carboplatina e Paclitaxel interrompido ao quinto ciclo para evitar progressão de aplasia medular constatada por biópsia de medula óssea. A possível hematotoxicidade do protocolo Paclitaxel e Carboplatina foi observada na conduta terapêutica da paciente, por sua progressão para uma apresentação atípica de aplasia pura adquirida crônica da série vermelha após administração desta associação de drogas.

The present case report describes the atypical presentation of a patient with invasive endometrioid adenocarcinoma that evolved with chronic acquired pure aplasia of the red series secondary to chemotherapy. A seventy-one-yearold patient, female, sought medical care for a three-month-old metrorrhagia evolution. The uterine curettage showed moderately differentiated invasive endometrioid adenocarcinoma. It was initiated an approach with chemotherapy regimen consisting of Carboplatin and Paclitaxel interrupted at the fifth cycle to prevent progression of spinal aplasia found by bone marrow biopsy. The possible hematoxicity of the patient, for its progression to an atypical presentation of chronic acquired aplasia of the red series after administration of this combination of drugs.

Female , Aged , Red-Cell Aplasia, Pure , Carcinoma, Endometrioid , Bone Marrow , Drug Therapy , Hematology , Antineoplastic Agents
Femina ; 49(7): 425-432, 2021. ilus
Article in Portuguese | LILACS | ID: biblio-1290592


As células glandulares atípicas representam 0,2% a 2,1% dos resultados dos testes de Papanicolaou. Mesmo com essa baixa prevalência, tem um significado importante no diagnóstico do câncer cervical e endometrial, tendo em vista que tais células e subcategorias, associadas à idade da paciente, podem prenunciar um número expressivo de doença intraepitelial, doença invasiva do endocérvix, endométrio e até neoplasias anexiais. E não se pode esquecer do importante número de resultados histológicos benignos, identificados no seguimento dessas pacientes, muitas vezes assintomáticas.(AU)

Atypical glandular cells represent 0,2% to 2,1% of Pap test results even with this low prevalence has an important significance in the diagnosis of cervical and endometrial cancer, considering that such cells and subcategories associated with the patient's age can predict a significant number of intraepithelial disease, invasive disease of the endometrium, endocervix and even adnexial neoplasms; no forgetting the important number of benign histological results, identified in the follow up of these patients, often asymptomatic.(AU)

Humans , Female , Uterine Cervical Neoplasms/pathology , Cervix Uteri/surgery , Carcinoma, Endometrioid/pathology , Conization , Adenocarcinoma in Situ/surgery , Adenocarcinoma in Situ/pathology , Colposcopy , Cytodiagnosis/methods
Clinics ; 76: e3318, 2021. tab, graf
Article in English | LILACS | ID: biblio-1350611


OBJECTIVE: To determine the role of RNA-binding protein with serine-rich domain 1 (RNPS1) in uterine corpus endometrial carcinoma (UCEC), the role of RNPS1 knockdown in UCEC development in vitro and in vivo, and the relationship between RNPS1 and mismatch repair (MMR) in UCEC. METHODS: We predicted the potential function of RNPS1 using bioinformatics systems. The expression of RNPS1 in tissues and cell lines was analyzed by western blotting and immunohistochemistry. The expression of RNPS1 in MMR was assessed using bioinformatics and western blotting. The proliferation and apoptosis of UCEC cells were assessed under RNPS1 knockdown conditions, and RNPS1 regulation in MMR was detected by suppressing Notch signaling. Associations between RNPS1 and gene mutations in UCEC and prognosis were analyzed. RESULTS: The RNPS1 level was higher in UCEC tumors than in normal tissues and tumors or RL952 cells. Prognostic outcomes were worse when UCEC showed abundant RNPS1 expression. Lentiviral RNPS1 knockdown weakened tumor cell proliferation and suppressed biomarker expression, reduced the tumor volume, promoted apoptosis in vitro and in vivo, and inhibited UCEC development. Increased MutS homolog 2 (MSH2) and MutS homolog 6 (MSH6) levels in MMR after RNPS1 knockdown were reversed by inhibiting Notch signaling. Furthermore, RNPS1 was associated with mutations in NAA11, C2orf57, NUPR1, and other genes involved in UCEC prognosis. CONCLUSION: RNPS1 may regulate the expression levels of MSH2 and MSH6 in MMR, enhancing the proliferation, development, and prognosis of UCEC through a Notch signaling pathway in UCEC. Our study offers a new method and strategy for delaying UCEC development through modulating MMR.

Humans , Female , Ribonucleoproteins/genetics , Endometrial Neoplasms/genetics , Carcinoma, Endometrioid/congenital , Serine , RNA-Binding Proteins , Cell Line, Tumor , Microsatellite Instability
Rev. méd. Paraná ; 79(1): 46-51, 2021.
Article in Portuguese | LILACS | ID: biblio-1282398


Objetivo: analisar lesões endometriais de pacientes com câncer de mama em tratamento com Tamoxifeno® presentes nas histeroscopias e relacioná-las com a dose de medicamento utilizada, tempo de terapêutica, presença de lesões endometriais prévias e estado de pré ou pós menopausa. Método: estudo retrospectivo, transversal e analítico. Dados analisados pelo teste qui quadrado, p<0,05. Resultados: dentre as 75 histeroscopias analisadas, 12 eram normais (16%) e 63 apresentaram alteração endometrial (84%). Dentre os achados das histeroscopias, 49 foram pólipos endometriais (67.12%), 7 foram pólipos endocervicais (9.58%), 11 foram hiperplasia simples sem atipias (15.06%), 1 foi hiperplasia complexa sem atipias (1.36%), 1 foi hiperplasia complexa com atipias (1.36%), 2 foram leiomiomas (2.73%) e 2 foram adenocarcinoma endometrioide (2.73%). Conclusão: O Tamoxifeno® predispõe o aparecimento de lesões endometriais, que podem ser malignas. Nesse estudo, a incidência dessas lesões foi expressivamente maior do que os valores encontrados na literatura

Objective: To analyze the endometrial lesions in hysteroscopies of patients with breast cancer undergoing treatment with Tamoxifeno® and to relate them to the dose of medication used, time of therapy, presence of previous endometrial lesions and pre or postmenopausal status. Method: retrospective, cross-sectional and analytical study. Data were statistically analyzed using the chi-square test, p <0.05. Results: Among the 75 hysteroscopies analyzed, 12 were normal (16%) and 63 presented endometrial alteration (84%). Among the hysteroscopic findings, 49 were endometrial polyps (67.12%), 7 were endocervical polyps (9.58%), 11 were simple hyperplasia without atypias (15.06%), 1 was complex hyperplasia without atypias (1.36%), 1 was complex hyperplasia with atypia (1.36%), 2 were leiomyomas (2.73%) and 2 were endometrioid adenocarcinoma (2.73%). Conclusion: Tamoxifen predisposes the appearance of endometrial lesions, which may be malignant. In this study, the incidence of these lesions was significantly higher than the values found in the literature

Humans , Female , Tamoxifen , Therapeutics , Breast Neoplasms , Hysteroscopy , Carcinoma, Endometrioid
Chinese Medical Journal ; (24): 2102-2109, 2021.
Article in English | WPRIM | ID: wpr-887662


BACKGROUND@#Endometrial cancer (EC) has been one of the most general cancers with respect to gynecological malignancies; however, there are debates on clinical strategies concerning treatments especially for patients with grade 3 (G3) endometroid endometrial cancer (EEC). Present study aimed to evaluate the lymphatic metastasis (LM) related factors and figure out the necessity of lymphadenectomy for G3 EEC patients.@*METHODS@#From January 2009 to April 2019, 3751 EC patients were admitted to Obstetrics and Gynecology Hospital of Fudan University. Clinical characteristics include age, grade, stage, and clinical pathological features. A total of 1235 EEC patients were involved in the multivariable analysis. Three hundred and eighty-one patients were involved in the survival analysis and the data attributed to sufficient follow-up information. Kaplan-Meier curve and log-rank test were utilized to analyze the survival rate.@*RESULTS@#Among the 1235 EEC patients, 181 (14.7%) were categorized as G3 and 1054 (85.3%) were grade 1 to grade 2 (G1-2). Multivariate analysis demonstrated that lymphovascular space invasion, adnexal involvement, and cervical stroma involvement were independent risk factors of LM in G3 cohort with odds ratio 3.4, 5.8, and 8.9; 95% confidence interval 1.1-10.6, 1.5-22.4, and 2.8-28.0, respectively. LM rates increased from 3.3% (3/92) to 75% (9/12) for G3 EEC cohort as related factor numbers increased from one to three. There were no differences between G3 and G1-2 EEC in overall survival and progression free survival. Additionally, no survival advantage was observed for G3 EEC patients at early stage with different plans of adjuvant treatment.@*CONCLUSIONS@#For G3 EEC patients without other pathological positive factor, the LM rate is lower than those with other pathological positive factor. Survival analysis showed no difference between G3 cohort and G1-2 cohort. Also, different adjuvant treatments had no impact on the overall survival for G3 EEC patients.

Female , Humans , Carcinoma, Endometrioid/pathology , Cross-Sectional Studies , Endometrial Neoplasms/pathology , Lymphatic Metastasis , Neoplasm Staging , Prognosis , Retrospective Studies
Rev. chil. obstet. ginecol. (En línea) ; 85(3): 263-269, jun. 2020. graf
Article in Spanish | LILACS | ID: biblio-1126161


ANTECEDENTES: existe una asociación demostrada entre endometriosis y algunas histologías del carcinoma epitelial de ovario. Por otra parte, se ha observado que hasta un 30% de las neoplasias de ovario se presentan de forma concomitante a neoplasias del endometrio. Para considerar la sincronicidad entre estos tumores, estos deben cumplir criterios anatomopatológicos estrictos como los descritos por scully. OBJETIVO: presentar un caso clínico de carcinoma endometrioide sincrónico de ovario y endometrio sobre focos de endometriosis, así como su diagnóstico y manejo. CASO CLÍNICO: paciente de 27 años que consulta por spotting intermenstrual. En la ecografía endocavitaria se observa un pólipo endometrial. Además, se describe un tumor anexial izquierdo de 42mm, trilobulado, con un polo sólido de 17×15mm. Se somete a una polipectomía histeroscópica y quistectomía ovárica laparoscópica. Asimismo, se reseca implante sospechoso en el fondo de saco posterior. El resultado anatomopatológico de las piezas quirúrgicas fue: pólipo endometrial con hiperplasia compleja con atipias y focos de adenocarcinoma endometrioide grado I; el tumor quístico ovárico izquierdo consistente con quiste endometriósico con focos de adenocarcinoma endometrioide. La lesión peritoneal corresponde a un implante de adenocarcinoma endometrioide grado I. El estudio de las características anatomopatológicas y la presencia del implante peritoneal sugieren el diagnóstico de un carcinoma endometrioide ovárico con origen en una lesión endometriósica sincrónico con un carcinoma endometrioide endometrial. CONCLUSIÓN: el diagnóstico diferencial entre la sincronicidad o diseminación de los tumores de ovario y endometrio de estirpe endometrioide supone un reto para el clínico y es fundamental para el correcto manejo de estas neoplasias.

BACKGROUND: there is a demonstrated association between endometriosis and some epithelial ovarian carcinoma histologies. On the other hand, it has been observed that up to 30% of ovarian neoplasms present concomitantly with endometrial neoplasms. To consider synchronicity between these neoplasms, they must meet strict pathological criteria such as those described by scully. OBJECTIVE: to introduce a case of an ovarian and endometrial synchronous endometrioid carcinoma implanted on endometriosis sites, as well as its diagnosis and management. CLINICAL CASE: a 27-year-old patient who consulted because of an intermenstrual spotting. The ultrasound image showed an endometrial polyp. Furthermore, a 42 mm left adnexal trilobal tumor with a 17×15mm solid pole was described. She underwent a hysteroscopic polypectomy and laparoscopic ovarian cystectomy. Likewise, resection of a suspicious implant in the posterior vaginal fornix was done. The pathological result of the surgical pieces was: endometrial polyp with complex hyperplasia with atypia and focal points of grade I endometrioid adenocarcinoma; the left ovarian cystectomy: endometriotic cyst with focal points of endometrioid adenocarcinoma. The peritoneal lesion corresponded to a grade I endometrioid adenocarcinoma implant. The study of the pathological characteristics and the presence of the peritoneal implant suggest the diagnosis of endometrioid ovarian carcinoma originated in a synchronous endometriotic lesion with endometrial endometrioid carcinoma. CONCLUSION: differential diagnosis between the synchronicity or spread of ovarian and endometrial endometrioid cell line carcinomas, is a great challenge and it is essential for the correct management of these neoplasms

Humans , Female , Adult , Ovarian Neoplasms/diagnosis , Endometrial Neoplasms/diagnosis , Carcinoma, Endometrioid/diagnosis , Neoplasms, Multiple Primary/diagnosis , Ovarian Neoplasms/surgery , Ovarian Neoplasms/pathology , Endometrial Neoplasms/surgery , Endometrial Neoplasms/pathology , Carcinoma, Endometrioid/surgery , Carcinoma, Endometrioid/pathology , Diagnosis, Differential , Neoplasms, Multiple Primary/surgery , Neoplasms, Multiple Primary/pathology
Rev. habanera cienc. méd ; 19(1): 102-111, ene.-feb. 2020. graf
Article in Spanish | LILACS, CUMED | ID: biblio-1099149


Introducción: La metástasis esplénica de un carcinoma endometrial es un acontecimiento clínico raro, con solo 13 casos documentados en la literatura, revisada. La evolución de esta metástasis, en una paciente atendida, en nuestra Institución, fue el motivo para publicar este trabajo. Hay otras enfermedades oncológicas que en su evolución de progresión o recaída cursan con este tipo de cuadro clínico donde el tratamiento quirúrgico es fundamental y así complementar con tratamiento de quimioterapia. Se hizo una revisión en publicaciones cubanas no se encontró reporte del tema. Objetivo: Presentar un caso con un adenocarcinoma de endometrio tipo endometroide que metastiza al bazo con histología de células claras. Presentación: Paciente de 45 años, con diagnóstico de adenocarcinoma de endometrio con estadiamiento quirúrgico pT3A Nx Mo etapa IIIA Grado 2; este estadiamiento es el anterior a 2009, llevó su tratamiento quirúrgico y radioterapia complementaria, controlada por 21 meses. En consulta de seguimiento se diagnostica metástasis al bazo, por lo que se realiza esplenectomía y es tratada con quimioterapia; fue atendida por el equipo multidisciplinario de ginecología oncológica; las investigaciones realizadas estuvieron basadas en inmuhistoquimica, imageneología y tratamiento de soporte cuando lo necesitó. Conclusiones: La metástasis esplénica por un cáncer de endometrio es rara, es el primero reportado en Cuba, los estudios inmuhistoquímicos y de imágenes son fundamentales(AU)

Introduction: Splenic metastasis from endometrial carcinoma is a rare clinical event with only 13 documented cases in the literature reviewed. The evolution of a patient with this metastasis attended in our institution was the reason that motivated us to publish this work. There are other oncological diseases that are accompanied by this clinical picture during their evolution of progression where surgical treatment complemented with chemotherapy treatment is essential. A literature review was carried out in Cuban publications, but no reports on the topic were found. Objective: The aim of this work is to present an endometroid type case endometrium adenocarcinoma which metastasizes to the spleen with clear cell histology. Case presentation: Forty-five-year-old patient with diagnosis of endometrium adenocarcinoma with surgical stage pT3a Nx Mo stage IIIA Grade 2; this quantification was defined before 2009. The patient underwent surgical treatment which was complemented with radiotherapy and then followed for 21 months. In the follow-up consultation, spleen metastasis was diagnosed; so she underwent splenectomy and was treated with chemotherapy. She was treated by the multidisciplinary gynecologic oncology team; the investigations performed were based on immuhistochemistry, imaging, and supportive treatment whenever needed. Conclusions: Splenic metastasis from endometrial cancer is rare; it is the first case reported in Cuba. Immuhistochemical and imaging studies are essential(AU)

Humans , Female , Middle Aged , Splenic Neoplasms/complications , Endometrial Neoplasms/complications , Carcinoma, Endometrioid/diagnosis
Rev. medica electron ; 42(1): 1597-1606, ene.-feb. 2020. graf
Article in Spanish | LILACS, CUMED | ID: biblio-1127017


RESUMEN Introducción: la función del endometrio está regida por el eje hipotálamo hipofisario mediante las hormonas sexuales por lo que es vulnerable a los desórdenes de este sistema los que provocan diferentes trastornos funcionales que se traducen en alteraciones morfológicas. Es fundamental su estudio para el diagnóstico de patologías que son un problema de salud en la población femenina. Objetivo: determinar las diferencias morfométricas para el diagnóstico histopatológico diferencial entre la hiperplasia endometrial compleja, el adenocarcinoma endometrioide y en el endometrio proliferativo normal, en el municipio Matanzas, enero2014 -2015. Material y Métodos: se realizó un estudio observacional descriptivo de corte transversal y se aplicó morfometría a una muestra de 30 biopsias endometriales, con el objetivo de determinar las diferencias morfométricas para el diagnóstico histopatológico diferencial entre la hiperplasia endometrial compleja, el adenocarcinoma endometrioide y en el endometrio proliferativo normal. Resultados: el área total de la glándula fue la variable analizada que mostró mayores valores y reflejó marcadas diferencias entre la hiperplasia endometrial compleja, el adenocarcinoma endometrioide y el endometrio proliferativo normal, seguida por la altura del epitelio por tanto existen diferencias cuando se estudian variables que tiene en cuenta la morfología glandular. Conclusiones: existen diferencias morfométricas entre la hiperplasia endometrial y el adenocarcioma endometroide cuando se estudian variables que tienen en cuenta la morfología y arquitectura glandular (AU).

SUMMARY Introduction: the endometrium function is ruled by the pituitary- hypothalamus axis by means of sexual hormones; therefore it is vulnerable to the disorders of this system provoking different functional disorders resulting in morphological alterations. It is very important to study them for the sake of the diagnosis of diseases that are a health problem in female population. Objective: to determine the morphometric differences for the differential histopathological diagnosis among the complex endometrial hyperplasia, the endometrioid adenocarcinoma and the normal proliferative endometrium e, in the municipality of Matanzas, in the period January 2014-2015. Methods: a cross-sectional descriptive observational study was carried out applying morphometry to a sample of 30 endometrial biopsies, with the objective of determining the morphometric differences for the differential histopathological diagnosis among the complex endometrial hyperplasia, endometrial adenocarcinoma and normal proliferative endometrium. Results: the gland total area was the used variable showing more values and revealed stark differences among complex endometrial hyperplasia, endometrioid adenocarcinoma and normal proliferative endometrium, followed by the epithelium height; hence there are differences when variables are studied taking into account glandular morphology. Conclusions: there are morphometric differences between endometrial hyperplasia and endometrioid adenocarcinoma when there are studied variables taking into account glandular morphology and architecture (AU).

Humans , Male , Female , Carcinoma, Endometrioid/diagnosis , Endometrial Hyperplasia/diagnosis , Multivariate Analysis , Endometrium/pathology , Organism Forms
Journal of Peking University(Health Sciences) ; (6): 570-577, 2020.
Article in Chinese | WPRIM | ID: wpr-942041


OBJECTIVE@#To compare the expression patterns of microRNA (miRNA) between 144 Uygur and Han women with endometrial carcinoma and to investigate their clinical significance.@*METHODS@#Taqman miRNA low-density array was used to compare miRNA profiles between Uygur and Han women with non-endometrioid endometrial carcinoma (NEEC). Five miRNAs were further analyzed in the 144 endometrial cancers including 62 Uygur and 82 Han samples via real-time PCR to determine their expression patterns.@*RESULTS@#MiRNA expression profiles revealed that many miRNAs overexpressed or downregula-ted in one ethnic group, but did not express or changed slightly in the other ethnic group. Further detection in the 144 endometrial cancers showed that miR-141, miR-200a, and miR-205 overexpressed in both ethnic groups. In Uygur endometrioid endometrial carcinoma (EEC), tumors with miR-141/200a overexpression tended to be more aggressive in behavior, whereas in the Han group, EEC with miR-200a overexpression was relative mild. However, the NEEC with miR-200a overexpression also had aggressive clinicopathologic features in the Han women. MiR-145 and miR-143 expressed differentially between Uygur and Han groups, they overexpressed in the former and decreased in the latter (P<0.05). In the Uygur women miR-145/143 increased significantly in NEEC and there was a trend that NEEC exhibiting favorable clinicopathologic factors had higher miR-145 expression, and was statistically significant in tumors with myometrial invasion less than 1/2 thickness (P=0.042). By contrary, miR-145/143 decreased in Han group and EEC with worse clinicopathologic variables had lower expression although without statistical significance. NEEC in Han group had no such tendency.@*CONCLUSION@#Uygur and Han women might have different miRNA expression profiles. MiR-141/200a/205 overexpressed in endometrial carcinomas and miR-141/200a might behave differently between these two ethnic groups as well as in EEC and in NEEC. Although miR-145/143 showed inverse expression patterns between Uygur and Han women with endometrial cancer, they all exerted tumor suppression effect on endometrial cancer.

Female , Humans , Carcinoma, Endometrioid , China , Endometrial Neoplasms , Ethnicity , MicroRNAs , Real-Time Polymerase Chain Reaction
Autops. Case Rep ; 10(4): e2020176, 2020. tab, graf
Article in English | LILACS | ID: biblio-1131845


Primary broad ligament carcinoma is a very rare occurrence with 28 reported cases worldwide, to date. The epidemiology, treatment strategy and prognosis are still uncertain because of the scarcity of cases. Currently, all broad ligament carcinomas are managed similar to epithelial ovarian cancer. We report the case of a 43-year-old female with a prolonged complaint of abdominal pain and intermittent urinary retention, requiring frequent catheterization. She was diagnosed with obstructive right hydroureteronephrosis. The abdominal Contrast Enhanced Computed Tomography (CECT) revealed a well-defined heterogeneous lesion of 2.1х3х3.2cm size in the right lateral and posterior wall of the cervix. An ultrasound (USG)-guided Fine Needle Aspiration Cytology (FNAC) of the mass was done and it was suspected to be malignant. The patient underwent total abdominal hysterectomy, right salpingo-oophorectomy, pelvic lymph-nodal sampling, and peritoneal washing. Histological examination depicted an endometrioid adenocarcinoma of the broad ligament. She received adjuvant chemotherapy, followed by hormonal therapy. It has been five years since her surgery, and she is now alive and disease free.

Humans , Female , Adult , Ovarian Neoplasms , Adenocarcinoma/pathology , Broad Ligament/abnormalities , Carcinoma, Endometrioid/pathology , Carcinoma, Ovarian Epithelial
Rev. Soc. Bras. Clín. Méd ; 17(1): 7-10, jan.-mar. 2019. tab.
Article in Portuguese | LILACS | ID: biblio-1025951


Objetivo: Descrever o padrão histopatológico e identificar a incidência de carcinomatose peritoneal no momento do diagnóstico de mulheres diagnosticadas com neoplasia de ovário. Métodos: Trata-se de um estudo transversal e descritivo, baseado na análise secundária de dados correspondentes aos prontuários de mulheres adultas com diagnóstico de neoplasia de ovário de um serviço de referência em oncologia clínica. Foram analisados 40 prontuários entre janeiro de 2007 e janeiro de 2017. Resultados: Ao estadiamento segundo o sistema da International Federation of Gynecology and Obstetrics, três mulheres (7,5%) apresentavam estadiamento clínico (EC) II, três (77,5%) estágio ECIII com carcinomatose peritoneal/invasão da pelve e seis (15%) estágio ECIV com metástases à distância, especialmente para pulmão e fígado. Em relação ao padrão histopatológico, 20 mulheres apresentaram adenocarcinoma seroso papilífero de alto grau (50%), 4 (10%) adenocarcinoma seroso papilífero de baixo grau, 3 (7,5%) adenocarcinoma endometrioide, 3 (7,5%) tumor de teca/granulosa, 3 (7,5%) carcinoma de células claras, 3 (7,5%) tumores não classificados, 2 (5%) disgerminoma e 2 (5%) com cistoadenocarcinoma mucinosos. Conclusão: É nítida a necessidade de mais estudos envolvendo essa patologia, de modo a favorecer o diagnóstico e a intervenção em estágios mais precoces e reduzir desfechos desfavoráveis. (AU)

Objective: To describe the histopathological pattern, and to identify the incidence of peritoneal carcinomatosis at the time of the diagnosis of women diagnosed with ovarian neoplasm. Methods: This is a cross-sectional and descriptive study, based on the secondary analysis of data corresponding to the medical records of adult women diagnosed with ovarian neoplasm in a reference service of clinical oncology. A total of 40 medical records were analyzed between January 2007 and January 2017. Results: At the staging (FIGO system) of the International Federation of Gynecology and Obstetrics, three women (7.5%) had clinical staging (EC) II staging, 31 (77.5%) were in the ECIII stage, with peritoneal carcinomatosis/pelvic invasion, six (15%) were in the ECIV stage, with metastases at a distance, especially to lung and liver. Regarding the histopathological pattern, twenty women had high-grade papillary serous adenocarcinoma (50%), 4 (10%) with low-grade papillary serous adenocarcinoma, 3 (7.5%) with endometrioid adenocarcinoma, 3 (7.5%) with granulosa-theca tumor, 3 (7.5%) with clear cell carcinoma, 3 (7.5%) with unclassified tumors, 2 (5%) with dysgerminoma, two (5%) with mucinous cystadenocarcinoma. Conclusions: There is a clear need for further studies involving this pathology, in order to favor diagnosis and intervention at earlier stages and to reduce unfavorable outcomes. (AU)

Humans , Female , Adolescent , Adult , Middle Aged , Aged , Ovarian Neoplasms/diagnosis , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/epidemiology , Ovarian Neoplasms/complications , Palpation , Peritoneal Neoplasms/complications , Ascites/etiology , Thecoma/epidemiology , Uterine Hemorrhage/etiology , Weight Loss , Adenocarcinoma/epidemiology , Abdominal Pain/etiology , Medical Records/statistics & numerical data , Incidence , Cross-Sectional Studies , Cystadenocarcinoma, Mucinous/epidemiology , Carcinoma, Endometrioid/epidemiology , Adenocarcinoma, Clear Cell/epidemiology , Dysgerminoma/epidemiology , Neoplasm Metastasis , Neoplasm Staging/classification
Chinese Medical Journal ; (24): 161-170, 2019.
Article in English | WPRIM | ID: wpr-772854


BACKGROUND@#DNA methylation is involved in numerous biologic events and associates with transcriptional gene silencing, playing an important role in the pathogenesis of endometrial cancer. ESR1/PGR frequently undergoes de novo methylation and loss expression in a wide variety of tumors, including breast, colon, lung, and brain tumors. However, the mechanisms underlying estrogen and progesterone receptors (ER/PR) loss in endometrial cancer have not been studied extensively. The aims of this study were to determine the expression of DNA (cytosine-5)-methyltransferase 3A/3B (DNMT3A/3B) in endometrial cancer to investigate whether the methylation catalyzed by DNMT3A/3B contributes to low ER/PR expression.@*METHODS@#The clinicopathologic information and RNA-Seq expression data of DNMT3A/3B of 544 endometrial cancers were derived from The Cancer Genome Atlas (TCGA) uterine cancer cohort in May 2018. RNA-Seq level of DNMT3A/3B was compared between these clinicopathologic factors with t-test or one-way analysis of variance.@*RESULTS@#DNMT3A/3B was overexpressed in endometrioid carcinoma (EEC) and was even higher in non-endometrioid carcinoma (NEEC) (DNMT3A, EEC vs. NEEC: 37.6% vs. 69.9%, t = -7.440, P < 0.001; DNMT3B, EEC vs. NEEC: 42.4% vs. 72.8%, t = -6.897, P < 0.001). In EEC, DNMT3A overexpression was significantly correlated with the hypermethylation and low expression of the ESR1 and PGR (P < 0.05). The same trend was observed in the DNMT3B overexpression subgroup. In the ESR1/PGR low-expression subgroups, as much as 83.1% of ESR1 and 59.5% of PGR were hypermethylated, which was significantly greater than the ESR1/PGR high-expression subgroups (31.3% and 11.9%, respectively). However, the above phenomena were absent in NEEC, while DNMT3A/3B overexpression, ESR1/PGR hypermethylation, and low ER/PR expression occurred much more often. In univariate analysis, DNMT3A/3B overexpressions were significantly correlated with worse prognosis. In multivariate analysis, only DNMT3A was an independent predictor of disease-free survival (P < 0.05).@*CONCLUSIONS@#DNMT3A/3B expression increases progressively from EEC to NEEC and is correlated with poor survival. The mechanisms underlying low ER/PR expression might be distinct in EEC vs. NEEC. In EEC, methylation related to DNMT3A/3B overexpression might play a major role in ER/PR downregulation.

Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Carcinoma, Endometrioid , Genetics , Metabolism , Pathology , DNA (Cytosine-5-)-Methyltransferases , Genetics , Metabolism , DNA Methylation , Genetics , Endometrial Neoplasms , Genetics , Metabolism , Pathology , Estrogen Receptor alpha , Genetics , Metabolism , Gene Expression Regulation, Neoplastic , Immunohistochemistry , Prognosis