Diagnosis of a case of leptomeningeal metastasis from endometrial carcinoma by next-generation sequencing and cerebrospinal fluid cytology / 中华神经科杂志

Endometrial carcinoma is one of common malignant tumors in female reproductive system, but it is extremely rare in leptomeningeal metastasis. The clinical manifestations and signs of meningeal carcinomatosis are complex and not specific. It is difficult to get a precise diagnosis early, and it has high rate of misdiagnosis and missed diagnosis. Accurate diagnosis and treatment of a case of leptomeningeal metastasis from endometrial carcinoma by next-generation sequencing and cerebrospinal fluid cytology are reported. The patient is an elderly female with a history of endometrial cancer. The main manifestations were fever, headache and dizziness; cerebrospinal fluid cytology showed tumor cells; AKT1 gene and TP53 gene were detected in endometrial carcinoma tissue, plasma and cerebrospinal fluid by next-generation sequencing. After treatment with intrathecal chemotherapy, immunotherapy combined with anti angiogenesis, the patient′s condition still progressed gradually and died finally. The purpose of this case report is to raise clinical awareness of recognition and treatment in early meningeal metastasis of endometrial carcinoma.

Primary broad ligament adenocarcinoma

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.

Characteristic and clinical significance of microRNA expression between 144 Uygur and Han women with endometrial carcinoma / 北京大学学报(医学版)

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.

Padrão histopatológico e incidência de carcinomatose peritoneal ao diagnóstico em mulheres com câncer de ovário / Histopathological pattern and incidence of peritoneal carcinomatosis at diagnosis in women with ovarian cancer

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)

Multiple model parameters of intravoxel incoherent motion in differentiation of stage endometrial carcinoma and endometrial polyp / 中国医学影像技术

Objective: To investigate the value of the multiple model parameters of intravoxel incoherent motion (IVIM) in identification of stage endometrial carcinoma (EC) and endometrial polyp (EP). Methods: The clinical and imaging data of 31 patients with stage EC (group EC) and 14 patients with EP (group EP), confirmed by postoperative pathological examination, were retrospectively analyzed, all patients were performed on 1.5T MR (including IVIM sequence, b=0, 20, 50, 100, 150, 200, 400, 800, 1 200, 2 000, 3 000 s/mm2) before operation. The IVIM multi-model parameter values of the lesions were measured and compared between the two groups, including the standard apparent diffusion coefficient (ADC-stand), slow-apparent diffusion coefficient (ADC-slow), fast-apparent diffusion coefficient (ADC-fast), perfusion fraction (f), distributed diffusion coefficient (DDC) and water molecular diffusion heterogeneity index (α). The ROC curve was used to evaluate the differential diagnostic efficacy of IVIM parameters for stage EC and EP. Results: The ADC-stand value, ADC-slow value, f-value, DDC value and α value of the EC group were all less than the EP group, and the ADC-fast value was greater than the EP group (all P=0.001). ROC curve results showed the standard ADC value, ADC-slow value, ADC-fast value, f value, DDC value and α value had differential diagnostic value for stage EC and EP, the AUC was 0.885, 0.877, 0.919, 0.926, 0.906 and 0.902, respectively (all P<0.05). Conclusion: The multi-model parameters of IVIM sequence can effectively identify stage EC and EP.

Clinical application of TCGA molecular classification in endometrial endometrioid carcinoma / 中华病理学杂志

Objective@#To explore molecular characteristics of endometrial endometrioid cancer according to The Cancer Genome Atlas (TCGA) based molecular classification of endometrial carcinomas and to confirm simple and clinically applicable surrogate methodologies in pathological practice.@*Methods@#Two hundred and twenty-eight cases of endometrial endometroid adenocarcinomas (EnACs) collected from August 2001 to August 2017 from Peking University Health Science Center, Peking University Third Hospital were molecularly categorized by using Sanger sequencing for the exonuclease domain mutations (EDM) of POLE, and by immunohistochemistry for p53 and mismatch repair (MMR) proteins. The cohort was classified into polymerase-E exonuclease domain mutation (POLE EDM), mismatch repair deficiency (MMR-D), p53 abnormal (p53-abn) and p53 wild type (p53-wt) groups. The correlation between molecular subgroups and the clinical-pathological features including prognosis were analyzed.@*Results@#The cohort was distributed as follows: 11(4.8%) POLE EDM, 47(20.6%) MMR-D, 9(4.0%) p53-abn and 161(70.6%) p53-wt. p53-wt subgroup patients demonstrated significantly higher lymph node metastasis (P=0.011) and more advanced stage (P=0.036) than those of somatic hypermutation group cases (POLE EDM and MMR-D). In the FIGO grade 2-3 EnACs cohort, TCGA molecular subtyping was significantly correlated with progression-free survival and overall survival (P=0.043). POLE EDM subgroup had the best survival, while p53-abn subgroup had the worst.@*Conclusions@#Identification of POLE EDM and MMR-D subgroups provides independent and highly valuable prognostic information beyond established histological classification. Based on immunohistochemistry of MMR, p53 and POLE mutational analysis, this pragmatic molecular classification scheme can be served as a reliable surrogate for TCGA molecular classification, which has potential to be used routinely in Chinese pathological practice.

Expression of cluster proteins in endometrial carcinoma and its relationship with ER and PR / 中国基层医药

Objective@#To investigate the expression of cluster proteins in endometrial cancer tissues and its correlation with estrogen receptor (ER) and progesterone receptor (PR).@*Methods@#We selected 120 cases of endometrial cancer tissue specimens and 120 cases of normal endometrial tissue specimens from January 2013 to December 2017 in the Maternal and Child Health Hospital of Huzhou.The expression of cluster proteins, ER and PR in tissues were determined by immunohistochemistry.@*Results@#The positive rate of cluster proteins in the endometrial carcinoma tissues(89.2%) was higher than that in the normal endometrial tissues(13.3%) (χ2=145.067, P<0.05). The positive expression rates of ER and PR in the endometrial carcinoma tissues(60.0%, 56.7%) were lower than those in the normal endometrial tissues(100.0%, 100.0%) (χ2=93.490, 96.698, all P<0.05). The cluster proteins was negatively correlated with ER and PR in the endometrial carcinoma tissues (r=-0.472, -0.513, all P<0.05). The expression of cluster protein and ER in the endometrial carcinoma were associated with FIGO stage, depth of myometrial invasion and lymph node metastasis of endometrial carcinoma(83.1% vs.93.0%, 82.6% vs.98.0%, 97.6% vs.84.6%; 81.7% vs.29.2%, 91.3% vs.17.6%, 19.5% vs.82.1%) (χ2=6.628, 7.228, 4.779; 33.062, 66.292, 43.984, all P<0.05), and were not associated with age, degree of differentiation and tumor diameter (all P>0.05). The positive expression of PR in the endometrial carcinoma was correlated with the FIGO stage and depth of myometrial invasion of the endometrial carcinoma(78.9% vs.24.5%, 84.1% vs.20.0%, χ2=34.919, 48.577, all P<0.05), and were not associated with age, degree of differentiation, tumor diameter and lymph node metastasis (all P>0.05).@*Conclusion@#The development of endometrial cancer is related to the overexpression of cluster proteins, and the expression of cluster proteins may be regulated by estrogen and progesterone.

Expression of cluster proteins in endometrial carcinoma and its relationship with ER and PR / 中国基层医药

Objective To investigate the expression of cluster proteins in endometrial cancer tissues and its correlation with estrogen receptor ( ER) and progesterone receptor ( PR).Methods We selected 120 cases of endometrial cancer tissue specimens and 120 cases of normal endometrial tissue specimens from January 2013 to December 2017 in the Maternal and Child Health Hospital of Huzhou.The expression of cluster proteins ,ER and PR in tissues were determined by immunohistochemistry.Results The positive rate of cluster proteins in the endometrial carcinoma tissues(89.2%) was higher than that in the normal endometrial tissues (13.3%) ( χ2 ＝145.067,P＜0.05).The positive expression rates of ER and PR in the endometrial carcinoma tissues (60.0%,56.7%) were lower than those in the normal endometrial tissues (100.0%,100.0%) (χ2 ＝93.490,96.698,all P＜0.05).The cluster proteins was negatively correlated with ER and PR in the endometrial carcinoma tissues ( r＝－0.472,－0.513,all P＜0.05).The expression of cluster protein and ER in the endometrial carcinoma were associated with FIGO stage , depth of myometrial invasion and lymph node metastasis of endometrial carcinoma (83.1% vs.93.0%,82.6% vs. 98.0%,97.6% vs.84.6%;81.7% vs.29.2%,91.3% vs.17.6%,19.5% vs.82.1%) ( χ2 ＝6.628,7.228, 4.779;33.062,66.292,43.984,all P＜0.05),and were not associated with age ,degree of differentiation and tumor diameter (all P＞0.05).The positive expression of PR in the endometrial carcinoma was correlated with the FIGO stage and depth of myometrial invasion of the endometrial carcinoma (78.9% vs.24.5%,84.1% vs.20.0%,χ2 ＝34.919,48.577,all P＜0.05),and were not associated with age ,degree of differentiation,tumor diameter and lymph node metastasis (all P＞0.05).Conclusion The development of endometrial cancer is related to the overexpression of cluster proteins,and the expression of cluster proteins may be regulated by estrogen and progesterone .

Value of combined adjuvant chemotherapy and radiation on survival for stage III uterine cancer: is less radiation equal to more? / 부인종양

OBJECTIVE: Locally advanced endometrioid adenocarcinoma (LA-EAC) accounts for the majority of deaths for this cancer, yet there is no consensus on adjuvant treatment after surgery. Past studies suggest that combined modality treatment (CMT) may improve outcomes over treatment with chemotherapy (CT) or radiation therapy (RT, either external beam radiotherapy [EBRT] or vaginal brachytherapy [VBT]) alone. Using a large US-based population-based registry, we evaluated adjuvant CMT in LA-EAC and the relative benefit of regional EBRT compared to focused VBT. METHODS: We studied patients diagnosed with Stage III LA-EAC between 2004 and 2013 from the National Cancer Data Base (NCDB). We used Cox regression and a log-rank test to assess survival based on treatment with CT alone, EBRT alone, VBT alone, or CMT with EBRT and/or VBT. We used a χ2 test to compare covariates between patients receiving CMT with EBRT or VBT. RESULTS: Patients who received CMT had better survival than those who received CT or EBRT/VBT alone. Compared to CMT with VBT, patients who received CMT with EBRT were slightly older and had more advanced-stage or positive nodes, and fewer had lymph node surgery. We found no survival difference between CMT with EBRT and CMT with VBT even when categorizing patients as high or low risk according to age, grade, and stage (low-risk p=0.3460; high-risk p=0.2158). CONCLUSION: CMT was associated with superior survival outcomes compared to monotherapy. We observed no survival difference between radiation modalities in CMT, which highlights the effectiveness of a more focused treatment like brachytherapy.

Carcinomas de ovário associados à endometriose: expressão de marcadores proteicos de terapia alvo e prognóstico / Endometriosis-associated ovarian carcinomas: expression of protein biomarkers associated to target therapies and prognosis

Resumo: Introdução: endometriose é uma doença benigna, capaz de progredir extensamente e gerar clones atípicos. Considerada precursora dos carcinomas de células claras (CCOC) e endometrióide (EOC) de ovário, atualmente chamados carcinomas de ovário associados à endometriose (EAOC). Objetivos: comparar o perfil epidemiológico, a associação com endometriose e a expressão de marcadores imuno-histoquímicos para ARID1A, VEGF, PD-L1 e PARP-1 em mulheres com CCOC e EOC, e sua correlação com a sobrevida livre de progressão (SLP) e sobrevida global (SG). Métodos: estudo de coorte reconstituída, com 50 casos incluídos de CCOC e EOC tratados no CAISM-UNICAMP entre 1995 até 2016, acompanhados até 02/2017. Microarranjos de tecido com amostras de CCOC, EOC e endometriose foram corados com anticorpos monoclonais contra ARID1A, e para os biomarcadores proteicos VEGF, PD-L1, PARP-1 através de imuno-histoquímica. A expressão de ARID1A foi classificada (0 a 100) conforme a porcentagem de células não coradas. A expressão de VEGF, PD-L1 e PARP-1 foi classificada (0 a 300) conforme a multiplicação da porcentagem de células coradas por um fator da intensidade de expressão (ausente=0; fraco=1; moderado=2; forte=3). Idade ao diagnóstico; menopausa; índice de massa corpórea (IMC); CA-125; diagnóstico de endometriose; datas do diagnóstico, da progressão, do óbito e da última consulta foram recuperados dos prontuários. Comparação entre grupos foi realizada através de testes T e de ?2. A SLP (diferença de tempo entre o diagnóstico e a data de progressão) e a SG (diferença de tempo entre o diagnóstico e o óbito ou data da última data de consulta) foi avaliada através de curvas de Kaplan-Meyer e teste de Log-Rank ou regressão de COX. Resultados: 23 mulheres com CCOC (46%), e 27 com EOC (54%) foram incluídas; 80% tinham endometriose associada, 42% eram nulíparas, 42% eram pré-menopausa e CA125 foi elevado em todos estádios (FIGO I-II= média 614.7Ui/mL; FIGO III-IV= media 2361.2Ui/mL). A média de idade ao diagnóstico foi 7 anos menor em mulheres com EOC do que naquelas com CCOC. O CCOC foi mais diagnosticado em estágios iniciais quando associado à endometriose (p=0,03). O prognóstico dos EOC e CCOC em estádios iniciais foi semelhante (p=0,96). Os CCOC não associado à endometriose tiveram menor SG (p=0,04). A expressão de todos os biomarcadores esteve presente nos EAOC e na endometriose. O aumento da expressão de VEGF entre endometriose e câncer foi significativo (p=0,0002). A hiperexpressão de PARP-1 correlacionou-se negativamente com a SLP (p=0,03) e SG (p=0,01) em estádios iniciais. Conclusão: Os CCOC e EOC são comumente diagnosticados em estádios iniciais (FIGO I-II= 68%) e estão frequentemente associados à endometriose (80% dos casos). Quando associados à endometriose, os CCOC foram mais diagnosticados em estádios iniciais e tiveram SG maior. Houve elevada porcentagem de células com ARID1A mutado nos EAOC (>40%). VEGF se expressou mais intensamente nos CCOC e EOC que na endometriose, já a expressão de PD-L1 e de PARP-1 foi similar. Apenas a hiperexpressão de PARP-1 reduziu significativamente a SLP e a SG nos CCOC e EOC nos estádios iniciais(AU)

Abstract: Introduction: Endometriosis is a benign disease, able to progress widely and generate atypical clones. It is a precursor of clear cell ovarian carcinomas (CCOC) and endometrioid ovarian carcinomas (EOCs), now called endometriosis-associated ovarian carcinomas (EAOC). Objectives: To compare the epidemiological profile, association with endometriosis and the expression of immunohistochemical markers for ARID1A, VEGF, PD-L1 and PARP-1 in women with CCOC and EOC, and its correlation with progression-free survival (PFS) and overall survival (OS). Methods: A reconstituted cohort study with 50 cases of CCOC and EOC included. Cases were treated at CAISM-UNICAMP between 1995 and 2016, followed up until 02/2017. Tissue microarrays with CCOC, EOC and endometriosis samples were stained with monoclonal antibodies against ARID1A, and for VEGF, PD-L1, PARP-1 biomarkers by immunohistochemistry. The expression of ARID1A was classified (0 to 100) according to the percentage of unstained cells. The expression of VEGF, PD-L1 and PARP-1 was classified (0 to 300) multiplying the percentage of stained cells by an intensity of expression factor (absent=0, weak=1, moderate=2, strong=3). Age at diagnosis; menopause; BMI (body mass index); CA-125 levels; diagnosis of endometriosis; date of diagnosis, date of progression, date of death and date of last consultation were retrieved from the medical records. Comparison between groups was performed through T and ?2 tests. The PFS (difference in time between diagnosis and progression date) and OS (difference in time between diagnosis and death or the last date of consultation) was assessed using Kaplan-Meyer curves and Log-Rank test or COX multivariate models. Results: twenty-three women with CCOC (46%), and 27 with EOC (54%) were included; 80% had associated endometriosis, 42% were nulliparous, 42% were premenopausal, and CA125 was elevated at all stages (FIGO I-II = mean 614.7Ui / mL; FIGO III-IV = mean 2361.2Ui / mL). The mean age at diagnosis was 7 years lower in women with EOC than in those with CCOC. CCOC when associated with endometriosis were more diagnosed at early stages (p=0.03). The prognosis of EOC and CCOC at early stages was similar (p=0.96). CCOCs not associated with endometriosis had shorter OS (p=0.04). Expression of all biomarkers was present in the EAOC and endometriosis. The increase in VEGF expression between endometriosis and cancer was significant (p=0.0002). The overexpression of PARP-1 correlated negatively with PFS (p=0.03) and OS (p=0.01) at FIGO I-II stages. Conclusion: The diagnosis of women with EOC was made earlier than in those with CCOC. CCOC and EOC are commonly diagnosed in early stages (FIGO I-II - 68%) and were associated with endometriosis (80% of cases). When associated with endometriosis, clear cell carcinomas are more likely diagnosed at early stages, and the association of endometriosis with CCOC improves OS. There was a high percentage of cells with mutated ARID1A gene in EAOC (> 40%). VEGF was expressed more intensely in CCOC and EOC than in endometriosis, whereas expression of PD-L1 and PARP-1 was similar. Only the overexpression of PARP-1 significantly reduced PFS and OS in CCOC and EOC at early stages(AU)

DWI differential diagnosis of uterine carcinosarcoma and grade Ⅰ endometrioid adenocarcinoma / 中国医学影像技术

Objective To investigate the significance of ADC value and DWI relative signal intensity (rSI) in differential diagnosis of uterine carcinosarcoma and grade Ⅰ endometrioid adenocarcinoma (EA).Methods Totally 13 patients with uterine carcinosarcoma and 23 patients with grade Ⅰ EA which were all pathologically proved were enrolled.Conventional MRI and DWI were obtained in all 36 patients.The mean ADC values (ADC),minimum ADC values (ADCmin) and rSI were measured and compared between uterine carcinosarcoma and grade Ⅰ EA patients.Results The rSI of uterine carcinosarcoma (8.20±1.77) was significantly higher than that of grade Ⅰ EA (6.95±2.19,P=0.04).Taking rSI=7.42 as the diagnostic threshold,the area under the ROC curve was 0.71 (P＜0.05),and the sensitivity,specificity,accuracy was 69.23％,60.87％ and 61.11％,respectively.However,there was no statistical difference of ADC and ADCmin between uterine carcinosarcoma and grade Ⅰ EA patients (both P＞0.05).Conclusion ADC value is of limited significance in differential diagnosis of uterine carcinosarcoma and grade Ⅰ EA,whereas rSI is useful for the identification of these two diseases.

Clinicopathologic and survival analysis of synchronous primary endometrial and ovarian cancer / 中华妇产科杂志

Objective To demonstrate the clinicopathological characteristics and determine the prognostic factors for women with synchronous primary endometrial and ovarian cancer(SEOC). Methods A retrospective analysis of 63 pathologically proven cases of SEOC diagnosed in Peking Union Medical College Hospital from January 2000 to May 2018 was carried out. Results (1)Clinical features: mean age at diagnosis was(48.3±10.0)years, and the mean body mass index(BMI)was(23.4±3.7)kg/m2. The most common presenting symptom was abnormal uterine bleeding with a ratio of 73%(46/63). Forty-three patients(68%,43/63)were premenopausal, and 30%(19/63)were nulliparous.(2)Pathological features:for the endometrial cancer, 90% patients were diagnosed at stageⅠ, and 81% were low grade tumors(G1- G2). The histological type of endometrial cancer was mainly endometrioid carcinoma(86%)and majority (81%)of patients were proved without or with superficial myometrial invasion. For the ovarian cancer, 70% patients were diagnosed at stage Ⅰand 65% were low grade tumors(G1-G2). Sixty-two percent of ovarian cancers were endometrioid carcinoma and 68% of patients had unilateral involvement of the ovaries.(3) Treatment and prognosis: all patients underwent surgery, of which 56 (89%) underwent staging surgery including retroperitoneal lymphadenectomy, and 57(90%)received postoperative adjuvant therapy. The median follow-up time was 48.0 months(range, 2-176 months), and 13% of the patients experienced tumor recurrence during the follow-up period. The median time to recurrence was 38.5 months, and 6 patients (10%)died of tumor recurrence. The 5-year progression-free survival(PFS)and 5-year overall survival(OS) for all patients were 69% and 80%, respectively.(4)Prognostic factors: univariate analysis showed that the presence of lymphovascular space invasion(LVSI), non-endometrioid histology of ovarian cancer and stage of ovarian cancer above stageⅠwere associated with significantly worse PFS(P<0.05). LVSI, high grade of endometrial cancer, and above stage Ⅰof ovarian cancer were associated with significantly worse OS(P<0.05). On multivariate analysis, LVSI, non-endometrioid type ovarian cancer and stage of ovarian cancer above stageⅠwere associated with significantly worse PFS(P<0.05). In addition, LVSI and stage of ovarian cancer above stage Ⅰwere also associated with significantly worse OS(P<0.05). Conclusions Women with SEOC are young, premenopausal and have a favorable overall prognosis. Presence of LVSI, non-endometrioid type ovarian cancer and stage of ovarian cancer above stageⅠare independent prognostic factors for PFS,and stage of ovarian cancer above stageⅠare independent prognostic factors for OS.

Microcystic, elongated and fragmented invasion pattern in endometrial carcinoma: the clinicopathology analysis / 中华妇产科杂志

Objective To assess the clinical value for the clinicopathological features of microcystic elongated and fragmented(MELF)invasion in endometrial carcinoma(EEC). Methods The clinicopathological data of 108 cases of endometrial carcinoma with total hysterectomy, bilateral adnexectomy, and pelvic dissection were retrospectively analysis in Peking University People′s Hospital from April 2015 to October 2016. Twenty-five patients with endometrial carcinoma showing MELF invasion pattern were collected. We analyzed retrospectively the association of MELF pattern invasion with clinical pathology data and prognosis of the patients,partial immunohistochemical staining was implemented. MELF invasion was a special invasion pattern and characterized by microcystic, elongated, fragmented(composed of cluster cells)gland in muscular layer. Results The incidence rate was 23.1%(25/108). These patients mean age was (59.3 ± 10.9)years old. Four cases were premenopausal, and 21 were postmenopausal. Abnormal vaginal bleeding was the main clinical presentation. The lesions tend to appear adjacent to the tumor body. Sometimes, it may be appears away from the tumor body in the deep muscle layer. Lymph node metastasis were present in 5 cases(20%,5/25). Thirteen cases(52%,13/25)of them demonstrated lymph vascular space involvement(LVSI). The immunohischemical expression of ER,PR, Ki-67 and galectin-3 showing MELF invasion pattern were weaker than no showing MELF invasion pattern endometrial carcinoma, cktokeratin (CK) was showed diffuse strong positive expression, E-cadherin was moderately positive expression. All 25 cases were followed up for(23.2±5.9)months(14-33 months)after the therapy with no recurrence on metastasis. Conclusions MELF invasion pattern is a special invasion pattern in low-grade EEC. The incidence of LVSI and lymph node metastasis rate in endometrial carcinoma with MELF invasion are significantly increased. The prognosis of MELF invasion pattern may be poor.

Myoferlin Expression and Its Correlation with FIGO Histologic Grading in Early-Stage Endometrioid Carcinoma

BACKGROUND: For endometrioid carcinoma patients, International Federation of Gynecologists and Obstetricians (FIGO) histologic grading is very important for identifying the appropriate treatment method. However, the interobserver discrepancy with this three-tiered grading system is a serious potential problem. In this study, we used immunohistochemistry to analyze the relationship between FIGO histologic grading score and myoferlin expression. METHODS: We studied the endometrioid carcinoma tissues of 60 patients from Gyeongsang National University Hospital between January 2002 and December 2009. Immunohistochemical analysis of myoferlin was performed on tissue microarray blocks from surgical specimens. RESULTS: Myoferlin expression was observed in 58 of 60 patients. Moderate and strong myoferlin expression was observed in low-grade endometrioid carcinoma, while there was a tendency toward loss of myoferlin expression in high-grade endometrioid carcinoma (p < .001). CONCLUSIONS: Our study revealed that myoferlin loss is significantly correlated with high FIGO grade of endometrioid carcinoma.

The Potential Roles of MELF-Pattern, Microvessel Density, and VEGF Expression in Survival of Patients with Endometrioid Endometrial Carcinoma: A Morphometrical and Immunohistochemical Analysis of 100 Cases

BACKGROUND: In this study, we hypothesized that microcystic, elongated, fragmented (MELF)-pattern, vascular endothelial growth factor (VEGF) expression by cancer cells and microvessel density of cancer stroma may be associated with progression of endometrioid adenocarcinoma. METHODS: The study used data from the Belarus Cancer Registry and archival histological material of 100 patients with retrospectively known good (survival) and poor (disease progression and death) outcomes. All cases were immunohistochemically stained for CD34 and VEGF. Two independent samples were compared for the characteristics of signs, and obtained results were analyzed by receiver operating characteristic analysis, Mann-Whitney U test, χ² test (Yates correction), and Mantel-Cox test. Multivariate Cox hazard analysis and Spearman correlation test were used. A p-value of less than .05 was considered statistically significant. RESULTS: The observed survival rate of patients with endometrioid adenocarcinoma was significantly lower (p = .002) in MELF-pattern positive patients when compared with MELF-pattern negative patients. The overall survival rate of patients whose tumors had more than 114 vessels/mm² of tissue was significantly low (p < .001). Interestingly, a similar observation was found in patients with increased vessel area, evidenced by VEGF expression in the glandular tumor component. CONCLUSIONS: Our study suggests, for the first time, that these criteria may be used as risk factors of endometrioid adenocarcinoma progression during 5 years after radical surgical treatment. However, a large independent cohort of samples should be considered in the future to validate our findings.

Comparison of three different risk-stratification models for predicting lymph node involvement in endometrioid endometrial cancer clinically confined to the uterus / 부인종양

OBJECTIVE: To compare the clinical validity of the Gynecologic Oncology Group-99 (GOG-99), the Mayo-modified and the European Society for Medical Oncology (ESMO)-modified criteria for predicting lymph node (LN) involvement in women with endometrioid endometrial cancer (EC) clinically confined to the uterus. METHODS: A total of 625 consecutive women who underwent comprehensive surgical staging for endometrioid EC clinically confined to the uterus were divided into low- and high-risk groups according to the GOG-99, the Mayo-modified, and the ESMO-modified criteria. Lymphovascular space invasion is the cornerstone of risk stratification according to the ESMO-modified criteria. These 3 risk stratification models were compared in terms of predicting LN positivity. RESULTS: Systematic LN dissection was achieved in all patients included in the study. LN involvement was detected in 70 (11.2%) patients. LN involvement was correctly estimated in 51 of 70 LN-positive patients according to the GOG-99 criteria (positive likelihood ratio [LR+], 3.3; negative likelihood ratio [LR−], 0.4), 64 of 70 LN-positive patients according to the ESMO-modified criteria (LR+, 2.5; LR−, 0.13) and 69 of the 70 LN-positive patients according to the Mayo-modified criteria (LR+, 2.2; LR−, 0.03). The area under curve of the Mayo-modified, the GOG-99 and the ESMO-modified criteria was 0.763, 0.753, and 0.780, respectively. CONCLUSION: The ESMO-modified classification seems to be the risk-stratification model that most accurately predicts LN involvement in endometrioid EC clinically confined to the uterus. However, the Mayo-modified classification may be an alternative model to achieve a precise balance between the desire to prevent over-treatment and the ability to diagnose LN involvement.

Association between metabolic syndrome and prognosis of endometrioid carcinoma / 中华妇产科杂志

Objective To study the association between metabolic syndrome (MS) and prognosis of endometrioid carcinoma.Methods A total of 256 patients with endometrioid carcinoma at,Zhejiang Cancer Hospital between January,2001 and December,2008 were chosen.The deadline for follow up was December 2008.The general conditions(including age and body mass index),whether coupled with MS and it's risk factors(including waist circumference,fasting plasma glucose,triglycerides,high-densitylipoprotein,systolic and diastolic blood pressure) were analyzed.The outcome of 256 patients whether coupled with MS were analyzed using Kaplan-Meier curve.Relative risks were estimated using Cox proportional hazards regression model.Results A total of 256 cases were followed-up successfully.Sixtyfour (33.0％) cases coupled with MS among the 194 patients survived,while thirty-two (51.6％)coupled with MS from 62 cases died,there was significant difference between them (x2=6.953,P=0.008).The total fiveyear survival rate was 75.8％,the survival time was (78.0±3.4) months.The rate and the survival time of patients coupled with MS [66.7％,(67.0±2.4) months] were significatly lower than those coupled with no MS [81.3％,(85.0±4.0) months;P＜0.05].The Cox proportional hazards regression results showed that coupled with MS,body mass index ≥25 kg/m2,waist circumference＞80 cm,abnormol systolic and diastolic blood pressure,abnormal fasting plasma glucose and more than two components of definitions of MS were related to bad prognosis of endometrioid carcinoma(P＜0.05).Conclusion Metabolic syndrome may be lead to a bad prognosis of endometrioid carcinoma.

Clinicopathologic analysis of 14 cases of atypical polypoid adenomyoma of endometrium with the emphasis on its cancerous transformation / 中华妇产科杂志

Objective To analyze the clinicopathologic characteristics of atypical polypoid adenomyoma (APA) of endometrium,and investigate the special characteristics of cancerous transformation from APA.Methods Fourteen cases of APA were collected in General Hospital of People' s Liberation Army from January 2007 to March 2013.The clinical data,morphologic features,immunohistochemistry and the related literature were reviewed.Results The median age of the 14 patients was 38 years (ranged from 23 to 72 years),only 1 patient was postmenopausal.The most common symptom was irregular vaginal bleeding (4/14),and 4 patients were identified during routine physical examination for infertility.Among 14 cases,4 cases were diagnosed as well differentiated endometrioid adenocarcinoma originating from APA,and their median age was 35 years (ranged from 28 to 41 years); color Doppler flow imaging (CDFI) of ultrasound showed rich blood flow signal.The tumors with cancerous components were obviously larger than the usual APA (mean diameter:4.7 versus 1.8 cm).Histologically,irregular and branched glands were embedded in fibromuscular stroma and the glandular epithelium were atypical hyperplasia in varying degrees.While carcinoma developed in the APA,the sieve,solid and papillary structures were noticeable,and necrosis were common.Conclusions APA is a rare lesion of the uterus.Although the clinical behavior is benign in most cases,there may be possible for some cases developing carcinomas.If the APA mass is more than 4 cm in diameter,and microscopically demonstrates prominent sieve,solid,papillary structures and necrosis,the diagnosis of carcinoma developed from APA can be made.Thorough analysis should be done before the most proper therapeutic regimen is drawn up.

Clinical characteristics of 42 cases of malignant endometrial polyps / 中华妇产科杂志

Objective To investigate the clinicopathologic characteristics of premalignant and malignant endometrial polyps (EP) in premenopausal and postmenopausal women.Methods A retrospective analysis was conducted in 42 cases of premalignant and malignant EP from 1993 to 2012.Polyps were classified into premenopausal (group A,10 cases) and menopausal (group B,32 cases),including 26 cases of endometrioid adenocarcinoma,4 of clear cell carcinoma,9 of serous adenocarcinoma,and 3 of atypical hyperplasia.Results The prevalence rate of premalignant and malignant EP was 1.42％ (42/2 965),the prevalence rate of malignancy in postmenopausal and postmenopausal women was 0.48％ (10/2 064) and 3.55％ (32/901),respectively.The mean size of EP was (1.6 ± 0.8) cm,abnormal uterine bleeding was positive in 90％ (38/42) of cases.The EP pathological diagnosis showed all were endometrioid adenocarcinoma in group A,while there were 4 of clear cell carcinoma,9 of serous adenocarcinoma in group B.The mean size of EP was (1.1 ± 0.6) and (1.7 ± 0.9) cm in group A and B respectively (P ＜0.05).According to immunohistochemistry,all cases of group A were ER positive,but 41％ (11/27) of group B were ER negative (P =0.059).The PR positive rate was 8/9 and 56％ (15/27) in group A and B,respectively (P =0.169).Conclusions The risk of the EP malignancy rate is higher,while ER,PR positive rate are lower in postmenopausal womcn.Postmenopausal EP,especially accompanied by abnormal uterine bleeding and large polyps should be removed as soon as possible.

Study of claudin-4 in the diagnosis and treatment of endometrial carcinoma / 中华妇产科杂志

Objective To clarify the role of claudin-4 in endometrial tumorigenesis and explore claudin-4 be as potentially useful agent in the treatment of endometrial carcinoma.Methods The expression of claudin-4 in 62 endonetrioid endometrial carcinoma (EEC),30 atypical hyperplasia endometrial tissue and 60 human normal endometrium was determined using immunohistochemistry and realtime PCR.Ninety female BALB/c mice were transplanted with Ishikawa endometrial cancer cells,which were divided into three groups with different intraperitoneal treatments with cisplatin,paclitaxel and saline solution.After the observation period,the tumors were extracted and stained with monoclonal antibody against claudin-4.The messenger RNA expression of claudin-4 was also detected using real-time PCR.Results Among the EEC samples,34％ (21/62) showed medium staining for claudin-4 and 66％ (41/62) showed intense staining.In atypical hyperplasia group,27％ (8/30) showed weak staining,53％ (16/30) showed medium staining and 20％ (6/30) showed intense staining for claudin-4.Of the normal endometrial tissue,47％ (28/60) showed weak staining and 53％ (32/60) showed no staining for claudin-4.According to real-time PCR,the relative quantity of claudin-4 was 170 ± 12 in EEC group,89 ± 15 in atypical hyperplasia group and 18 ± 3 in normal endometrium.Compared with those in atypical hyperplasia group and normal endometrium group,the protein and mRNA expression of claudin-4 were significantly increased in the group of EEC (all P ＜ 0.05).In the study of Ishikawa xenografts,no significant changes in tumor volume and claudin-4 expression were shown in paclitaxel group compared with that in the control group.Nevertheless,a significant reduction of the tumor growth and a significant decrease in claudin-4 expression were observed in cisplatin group.After cisplatin treatment,the tumor volume was significantly decreased [(0.51 ±0.21) versus (0.73 ±0.12) cm3],and the mRNA expression of claudin-4 was also significantly decreased (153 ± 35 versus 273 ± 27).Conclusion These results demonstrate that claudin-4 is strongly expressed in EEC,which may be a useful biomarker to monitor the effects of chemotherapy in patients with endometrial carcinoma.