Cytopathological characterization of ascites for the diagnosis of serous ovarian carcinoma / 中华肿瘤杂志

Objective: To investigate the cytomorphological and immunocytochemical features of tumor cells in the ascites of ovarian plasmacytoma (SOC). Methods: Specimens of serous cavity effusions were collected from 61 tumor patients admitted to the Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2015 to July 2021, including ascites from 32 SOC, 10 gastrointestinal adenocarcinomas, 5 pancreatic ductal adenocarcinomas, 6 lung adenocarcinomas, 4 benign mesothelial hyperplasia and 1 malignant mesothelioma patients, pleural effusions from 2 malignant mesothelioma patients and pericardial effusion from 1 malignant mesothelioma. Serous cavity effusion samples of all patients were collected, conventional smears were made through centrifugation, and cell paraffin blocks were made through centrifugation of remaining effusion samples. Conventional HE staining and immunocytochemical staining were applied to observe and summarize cytomorphological characteristics and immunocytochemical characteristics. The levels of serum tumor markers carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were detected. Results: Of the 32 SOC patients, 5 had low-grade serous ovarian carcinoma (LGSOC) and 27 had high-grade serous ovarian carcinoma (HGSOC). 29 (90.6%) SOC patients had elevated serum CA125, but the difference was not statistically significant between them and patients with non-ovarian primary lesions included in the study (P>0.05); The serum CEA was positive in 9 patients with gastrointestinal adenocarcinoma and 5 patients with lung adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.001); The serum CA19-9 was positive in 5 patients with gastrointestinal adenocarcinoma and 5 patients with pancreatic ductal adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.05). The serum CA125, CEA and CA19-9 were within the normal range in 4 patients with benign mesothelial hyperplasia. LGSOC tumor cells were less heterogeneous and aggregated into small clusters or papillary pattern, and psammoma bodies could be observed in some LGSOC cases. The background cells were fewer and lymphocytes were predominant; the papillary structure was more obvious after making cell wax blocks. HGSOC tumor cells were highly heterogeneous, with significantly enlarged nuclei and varying sizes, which could be more than 3-fold different, and nucleoli and nuclear schizophrenia could be observed in some cases; tumor cells were mostly clustered into nested clusters, papillae and prune shapes; there were more background cells, mainly histiocytes. Immunocytochemical staining showed that AE1/AE3, CK7, PAX-8, CA125, and WT1 were diffusely positively expressed in 32 SOC cases. P53 was focally positive in all 5 LGSOCs, diffusely positive in 23 HGSOCs, and negative in the other 4 HGSOCs. Most of adenocarcinomas of the gastrointestinal tract and lung had a history of surgery, and tumor cells of pancreatic ductal adenocarcinoma tend to form small cell nests. Immunocytochemistry can assist in the differential diagnosis of mesothelial-derived lesions with characteristic "open window" phenomenon. Conclusion: Combining the clinical manifestations of the patient, the morphological characteristics of the cells in the smear and cell block of the ascites can provide important clues for the diagnosis of SOC, and the immunocytochemical tests can further improve the accuracy of the diagnosis.

Development of a nomogram for predicting survival of patients with ovarian serous cystadenocarcinoma after based on SEER database / 浙江大学学报·医学版

To develop a survival time prediction model for patients with ovarian serous cystadenocarcinoma after surgery. A retrospective analysis of 5906 postoperative patients with ovarian serous cystadenocarcinoma in the surveillance, epidemiology, and end results (SEER) database from 2010 to 2015 was performed. The independent risk factors for long-term survival were analyzed with multivariate Cox proportional hazard regression model. The nomogram of 3-year and 5-year survival was developed by using R language. The receiver operator characteristic (ROC) curve and were used to test the discrimination of the model and the calibration diagram was used to evaluate the degree of calibration of the prediction model. The survival curves was conducted by the risk factors. Cox proportional hazard regression model showed that age, race, histological grade (poorly differentiated and undifferentiated), stage T (T2a, T2b, T2c, T3a, T3b and T3c), and stage M (M1) were independent factors for the prognosis of patients with ovarian serous cystadenocarcinoma after surgery. A nomogram was developed by the R language tool for predicting the 3-year and survival of patients through age, race, histological classification, stage T and stage M. The C-index was 0.688 and the areas under ROC curve of the nomogram for predicting 3-year and 5-year survival were 0.708 and 0.716, respectively. The results of the calibration indicated that the predicted values were consistent with the actual values in the prediction models. The survival time of patients with high-risk factors was shorter than that of patients with low-risk factors (<0.05). The developed nomogram in this study can be used to predict 3-year and 5-year survival of postoperative patients with ovarian serous cystadenocarcinoma, and it may be beneficial to guide clinical treatment.

Brain metastasis in papillary serous adenocarcinoma of the endometrium / Metástase cerebral do adenocarcinoma seroso-papilífero do endométrio

Abstract Background Most endometrial cancers (75%) are diagnosed in early stages (stages I and II), in which abnormal uterine bleeding is the most frequent clinical sign.When the diagnosis is performed in stage IV, the most common sites of metastasis are the lungs, liver and bones. Central nervous system (CNS)metastasis is a rare condition. The aim of this study is to describe a case of uterine papillary serous adenocarcinoma of the endometrium that progressed to brain and bone metastases. Case Report We present the case of a 56-year-old woman with abnormal uterine bleeding and endometrial thickened echo (1.8 cm). A hysteroscopy with biopsy was performed, which identified poor differentiated serous adenocarcinoma of the endometrium. A total abdominal hysterectomy, with pelvic and para-aortic lymphadenectomy, was performed. Analysis of the surgical specimen revealed a grade III uterine papillary serous adenocarcinoma. Adjuvant radio/chemotherapy (carboplatin and paclitaxel-six cycles) was indicated. Sixteen months after the surgery, the patient began to complain of headaches. Brain magnetic resonance imaging demonstrated an expansile mass in the right parietal lobe, suggesting a secondary hematogenous implant subsequently confirmed by biopsy. She underwent surgery for treatment of brain metastasis, followed by radiotherapy. She died 12 months after the brain metastasis diagnosis due to disease progression. Conclusion Uterine papillary serous adenocarcinoma of the endometrium has a low propensity to metastasize to the brain. To the best of our knowledge, this is the fifth documented case of uterine papillary serous adenocarcinoma of the endometrium with metastasis to the CNS.

Resumo Fundamentos A maioria dos cânceres de endométrio (75%) é diagnosticada em estágios iniciais (estágios I e II), nos quais o sangramento uterino anormal é o sinalclínico mais frequente. Quando o diagnóstico é realizado no estágio IV, os locais mais comuns de metástase são os pulmões, o fígado e os ossos. A metástase para o sistema nervoso central (SNC) é uma condição rara. O objetivo deste estudo é descrever um caso de adenocarcinoma seroso-papilífero do endométrio que progrediu para metástases cerebral e óssea. Relato de Caso Apresentamos o caso de uma mulher de 56 anos com sangramento uterino anormal e eco endometrial espessado (1,8 cm). Foi realizada histeroscopia com biópsia que identificou adenocarcinoma seroso-papilífero pouco diferenciado do endométrio. Uma histerectomia abdominal total, com linfadenectomia pélvica e para-aórtica, foi realizada. A análise da peça cirúrgica revelou adenocarcinoma seroso-papilífero do endométrio grau III. Radioterapia adjuvante/quimioterapia (carboplatina e paclitaxel- seis ciclos) foi indicada.Dezesseismeses após a cirurgia, a paciente começou a se queixar de dores de cabeça. A ressonância magnética cerebral demonstrou uma massa expansiva no lobo parietal direito, sugerindo um implante hematogênico secundário posteriormente confirmado por biópsia. A paciente foi submetida a cirurgia para tratamento de metástase cerebral, seguida de radioterapia. A paciente morreu 12 meses após o diagnóstico de metástase cerebral devido à progressão da doença. Conclusão O adenocarcinoma seroso-papilífero do endométrio tem uma baixa propensão a metastizar para o cérebro. Até onde sabemos, este é o quinto caso documentado de adenocacinoma seroso-papilífero do endométrio com metástase para o SNC.

Relationship between the precursors of high grade serous ovarian cancer and patient characteristics: decreased incidence of the p53 signature in pregnant women / 부인종양

OBJECTIVE: To investigate the relationship between the precursors of high grade serous ovarian cancer (HGSOC) and the characteristics of patients with a low HGSOC risk in terms of the effects of pregnancy. METHODS: We prospectively examined consecutive cases in which the bilateral fallopian tubes were removed during benign gynecological or obstetric surgery and assessed the relationship between the patient characteristics, including parity and pregnancy, and the incidence of HGSOC precursors. All the fallopian tubes were examined by applying the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) Protocol. RESULTS: Of the 113 patients enrolled, 67 were gynecological and 46 were obstetric. The p53 signature was identified in 21 patients. No other precursors were identified. In a comparison of the p53 signature-positive and negative groups, parous women and pregnant women were significantly fewer in the p53 signature-positive group (53% vs. 86%, p=0.002, 10% vs. 47%, p=0.001, respectively). Current pregnancy was also associated with a significantly lower incidence of the p53 signature after multivariate adjustment (odds ratio [OR]=0.112; 95% confidence interval [95% CI]=0.017–0.731; p=0.022). Among gynecological patients, parous women were fewer in the p53 signature-positive group on univariate (47% vs. 73%, p=0.047) and multivariate analysis (OR=0.252; 95% CI=0.069–0.911; p=0.036). No other characteristics were associated with p53 signature positivity. CONCLUSIONS: The incidence of the p53 signature was significantly lower in parous women and pregnant women. This decreased incidence of early phase serous carcinogenesis may be one of the possible mechanisms underlying HGSOC risk reduction among parous women.

Cáncer de endometrio: reporte de un caso y revisión de la literatura / Endometrial Cancer. Case report and literature review

Antecedentes: El cáncer endometrial (CE) según las estadísticas es el tumor ginecológico más frecuente en países desarrollados, donde su incidencia ha ido en aumento. Históricamente, el CE se ha clasificado en dos tipos: Tipo I (endometrioide), representando el 80-90% de los casos; el tipo II (no endometrioide como el de células serosas y claras, carcinomas indiferenciados). Como dato importante, la mayoría de las pacientes son diagnosticadas cuando la enfermedad se encuentra en etapas tempranas o la lesión todavía está confinada al útero. El tratamiento convencional radica en una histerectomía primaria más salpingooforectomía bilateral, según el estadío de la enfermedad. Caso clínico: Paciente de 58 años de edad que ingresa al Hospital de San Marcos, Ocotepeque, con sangrado transvaginal de 1 mes de evolución, hipertensión crónica y obesidad tipo I. En el ultrasonido transvaginal se observó engrosamiento endometrial, pero en la biopsia se diagnosticó Adenocarcinoma Endometrial de tipo Endometroide Grado II-III de la FIGO. Conclusión: Ante la presencia de sangrado uterino anormal en mujeres peri y postmenopáusicas, con factores de riesgos asociados, se debe sospechar cáncer de endometrio...(AU)

Immunhistochemical analysis of Nuclear Factor Kappa Beta expression in etiopathogenesis of ovarian tumors

Abstract Purpose: To investigate the place of the transcription factor nuclear kappa B (NF-kB), which is a marker of chronic inflammation, in the etiology of the ovarian carcinoma. Methods: NFkB analysis with the immunohistochemical method has been performed. To evaluate immunohistochemical NF-kB expression in the ovarian tissue, the H-score method. H-score = ∑ Pi (i+1), where ''Pi'' is the percentage of stained cells in each intensity category (0-100%) and ''i'' is the intensity indicating weak (i=1), moderate (i=2) or strong staining (i=3). Results: It has been seen that, the mean H score is statistically significantly higher in the patient group with serous and musinous adenocarcinoma diagnosis than the two other patient groups (p<0.005). Conclusions: Factor nuclear kappa B is an important mediator that acts in the chronic inflammation. The highest expression rates are determined by the immunohistochemical method in the ovarian cancer group.

Identificação de microRNAs diferencialmente expressos em carcinomas serosos de alto grau de pacientes com distintas evoluções clínicas / Identification of microRNAs differentially expressed in high grade serous carcinomas of patients with different clinical evolutions

Introdução: O tratamento do câncer epitelial de ovário é baseado na combinação de cirurgia e quimioterapia (principalmente carboplatina e paclitaxel). Embora o tratamento seja eficiente em 80% dos casos, a taxa de sobrevida de 5 anos é baixa devido à alta taxa de recorrência e resistência ao tratamento medicamentoso. Os processos moleculares que influenciam na resposta terapêutica e mecanismos que acarretam na sobrevida das pacientes ainda não são completamente compreendidos, e por este motivo, torna-se necessário a identificação de moléculas que possibilitem a melhor compreensão. Muitos estudos relatam a importância dos miRNAs no desenvolvimento e progressão do câncer de ovário, entretanto, tendo em vista a heterogeneidade do câncer ovariano, este estudo se diferencia por selecionar uma casuística clinicamente homogênea. Neste contexto, o objetivo do presente estudo foi caracterizar o perfil da expressão de miRNAs em amostras clinicamente homogêneas de adenocarcinoma seroso de alto grau, a fim de identificar miRNAs que estão envolvidos no processo de resistência ao tratamento quimioterápico e capazes de diferenciar pacientes com distintas evoluções clínicas. Metodologia: Foram selecionadas trinta e três amostras de adenocarcinoma seroso de ovário de alto grau, provenientes do banco de tumores do A.C.Camargo Cancer Center, oriundas de cirurgia com ressecção ótima cujas pacientes tinham estadiamento III e passaram por acompanhamento clínico mínimo de 2 anos. Destas 25 amostras foram provenientes de tumor primário, 8 de metástases primárias pareadas de pacientes que apresentaram recidiva e 5 amostras de epitélio de tuba de falópio de pacientes sem histórico de câncer como controle normal. A identificação dos miRNAs diferencialmente expressos nas pacientes com distintos desfechos clínicos foi realizada através da plataforma de larga escala de expressão de miRNAs humanos (G4870A ­ ID 031181; 8x60K, Agilent Tecnologies). As probes foram filtradas e normalizadas utilizando o software BRB ArrayTool (v. 4.4.0). Os alvos foram preditos usando miRWalk 2.0 (http://www.umm.uni-heidelberg.de/apps/zmf/mirwalk/custom.html), em quatr diferentes algoritmos (miRWalk, RNA22, miRanda and Targetscan). Para a análise do perfil entre miRNAs e transcritos codificadores, 415 amostras foram obtidas do The Cancer Genome Atlas (TCGA) (http://tcga-data.nci.nih.gov/tcga/) e essa interação foi submetida a um teste de correlação de Pearson. Os miRNAs diferencialmente expressos em diferentes desfechos clínicos foram validados pela técnica de in situ hybridization (ISH) em 114 amostras de adenocarcinoma seroso de alto grau incluídas no TMA proveniente do departamento de Anatomina Patologica do Hospital AC Camargo e em diferentes amostras provenientes do TCGA. Os alvos dos miRNAs validados foram associados a sobrevida global e livre de doença em amostras do TCGA e confirmados em amostras contidas no TMA da casuística interna através da técnica de Imuno-histoquímica. Resultados: A análise de comparação da expressão diferencial de miRNAs entre controle normal e de seroso de alto grau seroso demonstrou que 365 miRNAs foram diferencialmente expressos e foram encontradas 613 interações inversamente correlacionadas. Os miRNAs miR-934 e miR-143 foram associados a pior sobrevida global em nossa casuística, o miR-503-5p com resistência a quimioterapia. Apenas o miR-934 foi validado no TCGA e pela técnica de ISH. O alvo FZD3 foi predito para o miR-934 e miR-143 e foi negativamente correlacionado com ambos miRNAs em células tumorais de ovário. A expressão da proteína FZD3 por imuno-histoquímica demonstrou que esse receptor não foi expresso na membrana celular e sim no citoplasma e núcleo nos tumores de alto grau seroso. Conclusão: Diversos miRNAs tem participação na progressão do tumor de ovário. O miR-934 foi encontrado aumentado nas amostras metastática e em tumores primários e foi associado a pior sobrevida global, bem como o aumento citoplasmático de FZD3, alvo do miR-934, contudo este não foi associado a expressão de Beta-catenina. Sugere-se assim que outras vias de sinalização possam estar envolvidas neste contexto

Introduction: The treatment of epithelial ovarian cancer is based on the combination of surgery and chemotherapy (mainly carboplatin and Plactaxel). Although treatment is effective in 80% of cases, the 5 year survival rate is low due to the high recurrence rate and drug treatment resistance. The molecular processes that influence the therapeutic response and mechanisms that lead to the patient's survival are not yet fully understood, and for this reason, it becomes necessary to identify molecules that allow the best understanding. Many studies report the importance of miRNAs in the development and progression of ovarian cancer, however, in view of the heterogeneity of ovarian cancer, this study differs by selecting a clinically homogeneous casuistic. In this context, the objective of the present study was to characterize the profile of the expression of miRNAs in clinically homogeneous samples of high-grade serous adenocarcinoma, in order to identify miRNAs that are involved in the process of resistance to chemotherapic treatment and able to differentiate patients with different clinical developments. Methodology: A total of 33 specimens of high-grade ovary adenocarcinoma were selected from the tumor Bank of the A C Camargo Cancer Center, extracted from surgery with optimal resection whose patients had staging III and passed through clinical accompaniment of at least 2 years. Of these 25 samples were derived from primary tumor, 8 from primary metastasis of relapsed patients (paired) and 5 samples from fallopian epithelium tube of patients with no history of cancer as normal control. The identification of MiRNAs differentially expressed in patients with different clinical outturns was performed through the large-scale human miRNAs expression platform (G4870A ­ ID 031181; 8x60K, Agilent Technologies). The probes have been filtered and normalized using the BRB ArrayTool Software (v. 4.4.0). The targets were predicted using MiRWalk 2.0 (http://www.umm.uni-heidelberg.de/apps/zmf/mirwalk/custom.html), in four different algorithms (MiRWalk, RNA22, MiRanda and Targetscan). For the profile analysis between MiRNAs and transcribed coders, 415 samples were obtained from the Cancer Genome Atlas (TCGA) (http://tcga-data.nci.nih.gov/tcga/) and this interaction was subjected to a Pearson correlation test. The MiRNAs differentially expressed in different clinical outcomes were validated by the in situ hybridization (ISH) technique in 114 samples of high-grade serous adenocarcinoma included in the TMA from the Department of Anatomina Patologica A.C.Camargo Hospital and in different samples from the TCGA. The targets of the validated miRNAs were associated with global survival and disease-free in samples of the TCGA and confirmed in samples contained in the TMA of the internal casuistic through the technique of Imunohistoquimica. Results: The comparison analysis between normal control and high degree serous demonstrated that 365 miRNAs were differentially expressed and were found 613 interactions inversely correlated. The MiRNAs mir-934 and mir-143 were associated with worse global survival in our casuistic, the mir-503-5p with chemotherapy resistance. Only the MiR-934 was validated in TCGA and ISH technique. The FZD3 target was predicted for the mir-934 and mir-143 and was negatively correlated with both miRNAs in ovarian tumor cells. The expression of the FZD3 protein by Imunohistoquimica demonstrated that this receptor was not expressed in the cellular membrane but in the cytoplasm and nucleus in the high-degree serous tumors. Conclusion: Several miRNAs have participation in the ovarian tumor progression. The mir-934 was found increased in the metastatic samples and in primary tumors and was associated with worse global survival, as well as the cytoplasmic increase of FZD3, target of the MiR-934, however this was not associated with the expression of Beta-catenin. It is suggested, thus, that other pathways may be involved in this context

Identificação de microRNAs diferencialmente expressos em carcinomas serosos de alto grau de pacientes com distintas evoluções clínicas / Identification of microRNAs differentially expressed in high grade serous carcinomas of patients with different clinical evolutions

Introdução: O tratamento do câncer epitelial de ovário é baseado na combinação de cirurgia e quimioterapia (principalmente carboplatina e paclitaxel). Embora o tratamento seja eficiente em 80% dos casos, a taxa de sobrevida de 5 anos é baixa devido à alta taxa de recorrência e resistência ao tratamento medicamentoso. Os processos moleculares que influenciam na resposta terapêutica e mecanismos que acarretam na sobrevida das pacientes ainda não são completamente compreendidos, e por este motivo, torna-se necessário a identificação de moléculas que possibilitem a melhor compreensão. Muitos estudos relatam a importância dos miRNAs no desenvolvimento e progressão do câncer de ovário, entretanto, tendo em vista a heterogeneidade do câncer ovariano, este estudo se diferencia por selecionar uma casuística clinicamente homogênea. Neste contexto, o objetivo do presente estudo foi caracterizar o perfil da expressão de miRNAs em amostras clinicamente homogêneas de adenocarcinoma seroso de alto grau, a fim de identificar miRNAs que estão envolvidos no processo de resistência ao tratamento quimioterápico e capazes de diferenciar pacientes com distintas evoluções clínicas. Metodologia: Foram selecionadas trinta e três amostras de adenocarcinoma seroso de ovário de alto grau, provenientes do banco de tumores do A.C.Camargo Cancer Center, oriundas de cirurgia com ressecção ótima cujas pacientes tinham estadiamento III e passaram por acompanhamento clínico mínimo de 2 anos. Destas 25 amostras foram provenientes de tumor primário, 8 de metástases primárias pareadas de pacientes que apresentaram recidiva e 5 amostras de epitélio de tuba de falópio de pacientes sem histórico de câncer como controle normal. A identificação dos miRNAs diferencialmente expressos nas pacientes com distintos desfechos clínicos foi realizada através da plataforma de larga escala de expressão de miRNAs humanos (G4870A ­ ID 031181; 8x60K, Agilent Tecnologies). As probes foram filtradas e normalizadas utilizando o software BRB ArrayTool (v. 4.4.0). Os alvos foram preditos usando miRWalk 2.0 (http://www.umm.uni-heidelberg.de/apps/zmf/mirwalk/custom.html), em quatr diferentes algoritmos (miRWalk, RNA22, miRanda and Targetscan). Para a análise do perfil entre miRNAs e transcritos codificadores, 415 amostras foram obtidas do The Cancer Genome Atlas (TCGA) (http://tcga-data.nci.nih.gov/tcga/) e essa interação foi submetida a um teste de correlação de Pearson. Os miRNAs diferencialmente expressos em diferentes desfechos clínicos foram validados pela técnica de in situ hybridization (ISH) em 114 amostras de adenocarcinoma seroso de alto grau incluídas no TMA proveniente do departamento de Anatomina Patologica do Hospital AC Camargo e em diferentes amostras provenientes do TCGA. Os alvos dos miRNAs validados foram associados a sobrevida global e livre de doença em amostras do TCGA e confirmados em amostras contidas no TMA da casuística interna através da técnica de Imuno-histoquímica. Resultados: A análise de comparação da expressão diferencial de miRNAs entre controle normal e de seroso de alto grau seroso demonstrou que 365 miRNAs foram diferencialmente expressos e foram encontradas 613 interações inversamente correlacionadas. Os miRNAs miR-934 e miR-143 foram associados a pior sobrevida global em nossa casuística, o miR-503-5p com resistência a quimioterapia. Apenas o miR-934 foi validado no TCGA e pela técnica de ISH. O alvo FZD3 foi predito para o miR-934 e miR-143 e foi negativamente correlacionado com ambos miRNAs em células tumorais de ovário. A expressão da proteína FZD3 por imuno-histoquímica demonstrou que esse receptor não foi expresso na membrana celular e sim no citoplasma e núcleo nos tumores de alto grau seroso. Conclusão: Diversos miRNAs tem participação na progressão do tumor de ovário. O miR-934 foi encontrado aumentado nas amostras metastática e em tumores primários e foi associado a pior sobrevida global, bem como o aumento citoplasmático de FZD3, alvo do miR-934, contudo este não foi associado a expressão de Beta-catenina. Sugere-se assim que outras vias de sinalização possam estar envolvidas neste contexto (AU)

Introduction: The treatment of epithelial ovarian cancer is based on the combination of surgery and chemotherapy (mainly carboplatin and Plactaxel). Although treatment is effective in 80% of cases, the 5 year survival rate is low due to the high recurrence rate and drug treatment resistance. The molecular processes that influence the therapeutic response and mechanisms that lead to the patient's survival are not yet fully understood, and for this reason, it becomes necessary to identify molecules that allow the best understanding. Many studies report the importance of miRNAs in the development and progression of ovarian cancer, however, in view of the heterogeneity of ovarian cancer, this study differs by selecting a clinically homogeneous casuistic. In this context, the objective of the present study was to characterize the profile of the expression of miRNAs in clinically homogeneous samples of high-grade serous adenocarcinoma, in order to identify miRNAs that are involved in the process of resistance to chemotherapic treatment and able to differentiate patients with different clinical developments. Methodology: A total of 33 specimens of high-grade ovary adenocarcinoma were selected from the tumor Bank of the A C Camargo Cancer Center, extracted from surgery with optimal resection whose patients had staging III and passed through clinical accompaniment of at least 2 years. Of these 25 samples were derived from primary tumor, 8 from primary metastasis of relapsed patients (paired) and 5 samples from fallopian epithelium tube of patients with no history of cancer as normal control. The identification of MiRNAs differentially expressed in patients with different clinical outturns was performed through the large-scale human miRNAs expression platform (G4870A ­ ID 031181; 8x60K, Agilent Technologies). The probes have been filtered and normalized using the BRB ArrayTool Software (v. 4.4.0). The targets were predicted using MiRWalk 2.0 (http://www.umm.uni-heidelberg.de/apps/zmf/mirwalk/custom.html), in four different algorithms (MiRWalk, RNA22, MiRanda and Targetscan). For the profile analysis between MiRNAs and transcribed coders, 415 samples were obtained from the Cancer Genome Atlas (TCGA) (http://tcga-data.nci.nih.gov/tcga/) and this interaction was subjected to a Pearson correlation test. The MiRNAs differentially expressed in different clinical outcomes were validated by the in situ hybridization (ISH) technique in 114 samples of high-grade serous adenocarcinoma included in the TMA from the Department of Anatomina Patologica A.C.Camargo Hospital and in different samples from the TCGA. The targets of the validated miRNAs were associated with global survival and disease-free in samples of the TCGA and confirmed in samples contained in the TMA of the internal casuistic through the technique of Imunohistoquimica. Results: The comparison analysis between normal control and high degree serous demonstrated that 365 miRNAs were differentially expressed and were found 613 interactions inversely correlated. The MiRNAs mir-934 and mir-143 were associated with worse global survival in our casuistic, the mir-503-5p with chemotherapy resistance. Only the MiR-934 was validated in TCGA and ISH technique. The FZD3 target was predicted for the mir-934 and mir-143 and was negatively correlated with both miRNAs in ovarian tumor cells. The expression of the FZD3 protein by Imunohistoquimica demonstrated that this receptor was not expressed in the cellular membrane but in the cytoplasm and nucleus in the high-degree serous tumors. Conclusion: Several miRNAs have participation in the ovarian tumor progression. The mir-934 was found increased in the metastatic samples and in primary tumors and was associated with worse global survival, as well as the cytoplasmic increase of FZD3, target of the MiR-934, however this was not associated with the expression of Beta-catenin. It is suggested, thus, that other pathways may be involved in this context (AU)

Adenocarcinoma sincrónico de alto grado de endometrio y ovario; a propósito de un caso clínico / Synchronous high-grade adenocarcinoma of the endometrium and ovary; about a clinical case

RESUMEN El cáncer sincrónico endometrial y ovárico (SEOC) representa alrededor de un 5-10% de las neoplasias de endometrio y ovario. Cuando no existe extensión locorregional y presentan un patrón histológico de bajo grado, actúan como si fueran dos tumores primarios independientes, en lugar de comportarse como un cáncer en estadio avanzado. Los mecanismos para diferenciar si su origen es metastásico o por el contrario, son tumores primarios independientes conlleva una gran dificultad y ha generado una importante controversia dentro del estudio de este tipo de neoplasias. En este artículo, exponemos el caso clínico de una paciente de 46 años que presenta un tumor sincrónico de endometrio y ovario en estadio IA, desconocido hasta el estudio histológico de la pieza quirúrgica.

ABSTRACT Endometrial and ovarian synchronous cancer (SEOC) accounts for about 5-10% of endometrial and ovarian neoplasms. When there is no local extension and they present a low-grade histological pattern, they act as if they were two independent primary tumours, instead of behaving as an advanced stage cancer. Therefore, the differentiation of its origin (metastatic or independent primary tumours) is fraught with difficulty and has generated a significant controversy in the study of this type of neoplasms. In this article, we present the clinical case of a 46-year-old patient presenting a synchronous tumor of the endometrium and ovary in IA stage, unknown until the histological study of the surgical sample.

High grade Ovarian Serous Carcinoma associated with Chronic Schistosomiasis / Philippine Journal of Obstetrics and Gynecology

@#Schistosomiasis has been established as a causative factor in urinary bladder, liver, colorectal and cervical cancer. However, its role in ovarian malignancy has not been described. With the premise that long-standing inflammation secondary to chronic infection predisposes to cancer by promoting an environment that cultivates genomic lesions and tumor initiation, we are left with an open question: Does chronic infection with schistosomiasis also predispose to ovarian cancer? In this paper, we presented a case of a 54-year-old diagnosed with high grade serous carcinoma of the ovary and fallopian tube with a history of chronic infection with Schistosomiasis. In this case, the infection caused neoplastic lesions in the right fallopian tube with subsequent seeding of malignant cells to the right ovary, indirectly causing the high grade serous ovarian carcinoma of the patient.

Expression of PH Domain Leucine-rich Repeat Protein Phosphatase, Forkhead Homeobox Type O 3a and RAD51, and their Relationships with Clinicopathologic Features and Prognosis in Ovarian Serous Adenocarcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Ovarian serous adenocarcinoma can be divided into low- and high-grade tumors, which exhibit substantial differences in pathogenesis, clinicopathology, and prognosis. This study aimed to investigate the differences in the PH domain leucine-rich repeat protein phosphatase (PHLPP), forkhead homeobox type O 3a (FoxO3a), and RAD51 protein expressions, and their associations with prognosis in patients with low- and high-grade ovarian serous adenocarcinomas.</p><p><b>METHODS</b>The PHLPP, FoxO3a, and RAD51 protein expressions were examined in 94 high- and 26 low-grade ovarian serous adenocarcinomas by immunohistochemistry. The differences in expression and their relationships with pathological features and prognosis were analyzed.</p><p><b>RESULTS</b>In high-grade serous adenocarcinomas, the positive rates of PHLPP and FoxO3a were 24.5% and 26.6%, while in low-grade tumors, they were 23.1% and 26.9%, respectively (P < 0.05 vs. the control specimens; low- vs. high-grade: P > 0.05). The positive rates of RAD51 were 70.2% and 65.4% in high- and low-grade serous adenocarcinomas, respectively (P < 0.05 vs. the control specimens; low- vs. high-grade: P > 0.05). Meanwhile, in high-grade tumors, Stage III/IV tumors and lymph node and omental metastases were significantly associated with lower PHLPP and FoxO3a and higher RAD51 expression. The 5-year survival rates of patients with PHLPP- and FoxO3a-positive high-grade tumors (43.5% and 36.0%) were significantly higher than in patients with PHLPP-negative tumors (5.6% and 7.2%, respectively; P< 0.05). Similarly, the 5-year survival rate of RAD51-positive patients (3.0%) was significantly lower than in negative patients (42.9%; P< 0.05). In low-grade tumors, the PHLPP, FoxO3a, and RAD51 expressions were not significantly correlated with lymph node metastasis, omental metastasis, Federation of Gynecology and Obstetrics stage, or prognosis.</p><p><b>CONCLUSIONS</b>Abnormal PHLPP, FoxO3a, and RAD51 protein expressions may be involved in the development of high- and low-grade ovarian serous adenocarcinomas, suggesting common molecular pathways. Decreased PHLPP and FoxO3a and increased RAD51 protein expression may be important molecular markers for poor prognosis, and RAD51 may be an independent prognosis factor, of high-grade, but not low-grade, ovarian serous adenocarcinomas.</p>

SIADH secundario a adenocarcinoma seroso de ovario tratado con tolvaptán / SIADH secondary to serous ovarian adenocarcinoma treated with tolvaptan

La hiponatremia es la alteración electrolítica más frecuente en el medio hospitalario, y en un 30% de los casos se debe a un síndrome de secreción inapropiada de vasopresina (SIADH). El SIADH está descrito como cuadro paraneoplásico endocrinológico en múltiples tumores, entre los que excepcionalmente se encuentra el de ovario y las neoplasias ginecológicas en general. Presentamos un caso de SIADH paraneoplásico por un citoadenocarcinoma seroso de ovario de alto grado, estadio IV. Se trata del primer caso de SIADH crónico por cáncer de ovario tratado con Tolvaptán. En el presente caso el objetivo de eunatremia se alcanzó con una dosis baja de acuarético, lo que apoya la elevada sensibilidad, ya previamente documentada, de los SIADH tumorales al tratamiento con Tolvaptán.

Hyponatremia is the most common electrolyte disturbance in hospitals, and 30% of cases are due to syndrome of inappropriate secretion of antidiuretic hormone (SIADH). SIADH is described as an endocrine paraneoplastic syndrome in multiple tumors including, ovary and gynecological malignancies in general, although these are exceptional. We report a case of paraneoplastic SIADH for high-grade serous ovarian cystoadenocarcinoma stage IV. This is the first case of chronic SIADH for ovarian cancer treated with Tolvaptan. In this case the target of eunatremia was reached with a low dose of aquaretic, which supports the high sensitivity, as previously documented, of paraneoplasic SIADH to Tolvaptan.

Efficacy of Postoperative Hormone Replacement Therapy on Prognosis of Patients with Serous Ovarian Carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Ovarian cancer is the most common cause of gynecological cancer-associated death. Iatrogenic menopause might adversely affect the quality of life and health outcomes in young female cancer survivors. We evaluated whether postoperative hormone replacement therapy (HRT) had a negative influence on the progression-free survival (PFS) of patients with papillary serous ovarian cancer (SOC).</p><p><b>METHODS</b>We retrospectively reviewed the medical records of patients with papillary SOC, treated from January 1980 to December 2009, who suffered from menopause with or without HRT. Clinical characteristics of patients were compared between the two groups (HRT and non-HRT). Blood samples were collected from all the participants to detect serum cancer antigen (CA) 125. Hazard ratios with 95% confidential intervals for each variable were calculated by univariable and multivariable conditional Logistic regression analyses.</p><p><b>RESULTS</b>Among 112 identified patients, 31 were HRT users and 81 were not. The two groups did not significantly differ in median age at diagnosis (t = 0.652, P = 0.513), International Federation of Gynecology and Obstetrics (FIGO) stage (χ2 = 0.565, P = 0.754), differentiation (χ2 = 1.728, P = 0.422), resection status (χ2 = 0.070, P = 0.791), relapse (χ2 = 0.109, P = 0.741), chemotherapy course (t = -1.079, P = 0.282), follow-up interval (t = 0.878, P = 0.382), or PFS (t = 0.580, P = 0.562). Median Kupperman score at the onset of HRT was 30.81 and 12.19 after the therapy (t = 3.302, P = 0.001). According to the analysis, the strongest independent variables in predicting PFS were FIGO stage and disease that was not optimally debulked.</p><p><b>CONCLUSIONS</b>Postoperative HRT is not a prognostic factor for PFS of patients with papillary SOC. However, multicenter studies are needed to verify and extend our findings.</p>

Relationship between P53 Protein Expression and Prognosis of Advanced Ovarian Serous Adenocarcinoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the expression of P53 protein in the advanced ovarian serous adenocarcinoma and explore its potential correlation with the clinicopathological features and prognosis of ovarian cancer.</p><p><b>METHODS</b>The immunohistochemical staining was used to detect the expression of P53 protein in 183 patients with advanced ovarian serous adenocarcinoma. The correlation of P53 protein with the clinicopathological features and its significance in the assessment of prognosis were explored.</p><p><b>RESULTS</b>The P53 protein expression was positive in 62.8% of the patients. Chi-square test showed that the overexpression of P53 protein was positively correlated with the elevation of serum CA125 and the two-tier grading of ovarian serous adenocarcinoma (P<0.001, P=0.038). Univariate analysis suggested that the prognosis of patients was associated with two-tier grading (P=0.007), lymph node metastasis (P=0.036), preoperative serum CA125 level (P=0.002), and P53 overexpression (P<0.001). Multivariate analysis showed that the International Federation of Gynecology and Obstetrics stage (P=0.038), lymph node metastasis (P=0.002), and overexpression of P53 (P=0.001) were independent prognostic factors.</p><p><b>CONCLUSION</b>The P53 protein expression is closely related to the prognosis of advanced ovarian serous adenocarcinoma and can be used as an important indicator for predicting the prognosis.</p>

The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients / 부인종양

OBJECTIVE: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. METHODS: In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and < or = median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients' survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. RESULTS: Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5-silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells. CONCLUSION: Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization.

Incidence of epithelial ovarian cancer according to histologic subtypes in Korea, 1999 to 2012 / 부인종양

OBJECTIVE: To investigate trends in the incidence of epithelial ovarian cancer (EOC), according to histologic subtypes, in Korean women between 1999 and 2012. METHODS: Data from the Korea Central Cancer Registry recorded between 1999 and 2012 were evaluated. The incidences of EOC histologic subtypes were counted. Age-standardized incidence rates (ASRs) and annual percentage changes (APCs) in incidence rates were calculated. Patient data were divided into three groups based on age (59 years), and age-specific incidence rates were compared. RESULTS: Overall, the incidence of EOC has increased. Annual EOC cases increased from 922 in 1999 to 1,775 in 2012. In 1999, the ASR was 3.52 per 100,000 and increased to 4.79 per 100,000 in 2012 (APC, 2.53%; p<0.001). The ASRs in 2012 and APCs between 1999 and 2012 for the four major histologic subtypes were as follows (in order of incidence): serous carcinoma (ASR, 2.32 per 100,000; APC, 4.34%; p<0.001), mucinous carcinoma (ASR, 0.73 per 100,000; APC, -1.05%; p=0.131), endometrioid carcinoma (ASR, 0.51 per 100,000; APC, 1.48%; p=0.032), and clear cell carcinoma (ASR, 0.50 per 100,000; APC, 8.13%; p<0.001). In the sub-analyses based on age, clear cell carcinoma was confirmed as the histologic subtype whose incidence had increased the most since 1999. CONCLUSION: The incidence of EOC is increasing in Korea. Among the histologic subtypes, the incidence of clear cell carcinoma has increased markedly across all age groups since 1999.

Combined modality therapy in the adjuvant treatment of uterine serous carcinoma / 부인종양

No abstract available.

Estimation of Prognostic Marker Genes by Public Microarray Data in Patients with Ovarian Serous Cystadenocarcinoma

PURPOSE: Lymphatic invasion (LI) is regarded as a predictor of the aggressiveness of ovarian cancer (OC). However, LI is not always the major determinant of long-term patient survival. To establish proper diagnosis and treatment for OC, we analyzed differentially expressed genes (DEGs) for patients with serous epithelial OC, with or without LI, who did or did not survive for 5 years. MATERIALS AND METHODS: Gene expression data from 63 patients with OC and LI, and 35 patients with OC but without LI, were investigated using an Affymetrix Human Genome U133 Array and analyzed using The Cancer Genome Atlas (TCGA) database. Among these 98 patients, 16 survived for 5 years or more. DEGs were identified using the Bioconductor R package, and their functions were analyzed using the DAVID web tool. RESULTS: We found 55 significant DEGs (p<0.01) from the patients with LI and 20 highly significant DEGs (p<0.001) from those without it. Pathway analysis showed that DEGs associated with carbohydrate metabolism or with renal cell carcinoma pathways were enriched in the patients with and without LI, respectively. Using the top five prognostic marker genes, we generated survival scores that could be used to predict the 5-year survival of patients with OC without LI. CONCLUSION: The DEGs identified in this study could be used to elucidate the mechanism of tumor progression and to guide the prognosis and treatment of patients with serous OC but without LI.

Association of family risk and lifestyle/comorbidities in ovarian cancer patients / Associação de história familiar e estilo de vida a comorbidades em pacientes com câncer de ovário.

Summary Objectives: to analyze factors that might indicate familial predisposition for ovarian cancer in patients diagnosed with this disease. Methods: in a prospective single center cohort study at the Institute of Cancer of the State of São Paulo (ICESP), 51 women diagnosed with ovarian cancer were included. Familial predisposition for ovarian cancer was defined as having a higher than 10% chance of having a BRCA1/2 mutation according to the Manchester scoring system, a validated method to assess the likelihood of mutation detection. Each patient was interviewed with a standardized questionnaire on established risk factors for ovarian cancer and other factors that might influence the risk to develop ovarian cancer. Logistic regression analyses were performed to estimate the impact of the evaluated factors on the likelihood of mutation detection, by calculating odds ratios and 95% confidence intervals. Results: seventeen out of 51 patients had a family history of breast and/or ovarian cancer, four patients had a history of breast or endometrial cancer, 11 were diagnosed before the age of 50, and 12 presented a risk of familial predisposition to ovarian cancer higher than 10%. Patients with comorbidities, such as hypertension, diabetes, hormonal disorders, dyslipidemia and psychiatric conditions, presented a lower chance of having a familial predisposition for ovarian cancer (OR: 0.22; 95% CI: 0.06-0.88; p=0.03). Conclusion: in this study, having comorbidities was associated with a lower risk of having a familial predisposition for ovarian cancer. Other factors associated with the risk of ovarian cancer did not have an impact on this predisposition. .

Resumo Objetivos: analisar fatores que possam indicar uma predisposição familiar ao câncer de ovário em pacientes com este diagnóstico. Métodos: em estudo de coorte prospectiva realizado no Instituto do Câncer do Estado de São Paulo (ICESP), foram incluídas 51 mulheres diagnosticadas com câncer de ovário entre janeiro de 2009 e dezembro de 2011. Predisposição familiar para câncer de ovário foi definida como um risco maior de 10% de apresentar uma mutação em BRCA1/2, de acordo com o sistema de pontes de Manchester, um método validado para avaliar a probabilidade de detecção de mutação nesses genes. Cada paciente foi entrevistada com um questionário padronizado, abordando fatores de risco para câncer de ovário e outros fatores que pudessem influenciar o risco de desenvolver a doença. O impacto dos fatores avaliados na probabilidade de detecção da mutação foi avaliado com regressões logísticas. Resultados: dezessete das 51 pacientes referiram história familiar de câncer de mama e/ou ovário, quatro pacientes apresentavam antecedente pessoal de câncer de mama ou endométrio, 11 haviam sido diagnosticadas antes dos 50 anos e 12 apresentaram um risco maior que 10% de predisposição familiar a câncer de ovário. Pacientes com comorbidades como hipertensão, diabetes, disfunções hormonais, dislipidemia e distúrbios psiquiátricos apresentaram menor risco de predisposição familiar ao câncer de ovário (OR: 0.22; IC 95%: 0.06-0.88; p=0.03). Conclusão: neste estudo, apresentar alguma comorbidade foi associado a um menor risco de ter uma predisposição familiar ao câncer de ovário. Outros fatores associados ao risco de câncer de ovário não tiveram nenhum impacto sobre esta predisposição. .

Key nodes of a microRNA network associated with the integrated mesenchymal subtype of high-grade serous ovarian cancer / 癌症

Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition (EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentially present in mesenchymal cells. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas (TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This "paradox" can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating mRNA and microRNA (miRNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major miRNAs and 214 mRNAs. Among the 8 miRNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 miRNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer.