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1.
Medicine (Baltimore) ; 99(52): e23849, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350775

RESUMO

BACKGROUD: The expression of microRNA-21 has been shown to be associated with the prognosis in patients with malignant tumors. However, its prognostic value in epithelial ovarian carcinoma (EOC) remains controversial. This meta-analysis aimed to synthesize available data to clarify the association between microRNA-21 expression levels and clinical prognosis in EOC patients. METHODS: Eligible literatures were searched from Embase, Google Scholar, PubMed, Web of Science, Medline, Cochrane Library, China Scientific Journal Database, China National Knowledge Infrastructure, Chinese BioMedical Database and Wanfang Database to identify eligible studies. Papers in English or Chinese published from their inception to November 2020 will be included. Methodological quality for each eligible trial will be assessed by using the Newcastle-Ottawa Quality Assessment Scale. Odds ratios or hazards ratios with corresponding 95% confidence intervals were pooled to estimate the prognosis value of microRNA-21 by using Stata 14.0 and Review Manager 5.3 software. RESULTS: This study will provide a high-quality evidence-based medical evidence of the correlations between microRNA-21 expression and overall survival and disease-free survival. CONCLUSION: The findings of this systematic review will show the effect of high expression of microRNA-21 on the prognosis of EOC patients. TRIAL REGISTRATION NUMBER: INPLASY2020110064.


Assuntos
Carcinoma Epitelial do Ovário , MicroRNAs/análise , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/metabolismo , Correlação de Dados , Feminino , Humanos , Metanálise como Assunto , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/metabolismo , Prognóstico , Projetos de Pesquisa , Análise de Sobrevida , Revisões Sistemáticas como Assunto , Transcriptoma
2.
Am J Hum Genet ; 107(4): 622-635, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32946763

RESUMO

Quantifying the functional effects of complex disease risk variants can provide insights into mechanisms underlying disease biology. Genome-wide association studies have identified 39 regions associated with risk of epithelial ovarian cancer (EOC). The vast majority of these variants lie in the non-coding genome, where they likely function through interaction with gene regulatory elements. In this study we first estimated the heritability explained by known common low penetrance risk alleles for EOC. The narrow sense heritability (hg2) of EOC overall and high-grade serous ovarian cancer (HGSOCs) were estimated to be 5%-6%. Partitioned SNP heritability across broad functional categories indicated a significant contribution of regulatory elements to EOC heritability. We collated epigenomic profiling data for 77 cell and tissue types from Roadmap Epigenomics and ENCODE, and from H3K27Ac ChIP-seq data generated in 26 ovarian cancer and precursor-related cell and tissue types. We identified significant enrichment of risk single-nucleotide polymorphisms (SNPs) in active regulatory elements marked by H3K27Ac in HGSOCs. To further investigate how risk SNPs in active regulatory elements influence predisposition to ovarian cancer, we used motifbreakR to predict the disruption of transcription factor binding sites. We identified 469 candidate causal risk variants in H3K27Ac peaks that are predicted to significantly break transcription factor (TF) motifs. The most frequently broken motif was REST (p value = 0.0028), which has been reported as both a tumor suppressor and an oncogene. Overall, these systematic functional annotations with epigenomic data improve interpretation of EOC risk variants and shed light on likely cells of origin.


Assuntos
Carcinoma Epitelial do Ovário/genética , Proteínas Correpressoras/genética , Cistadenocarcinoma Seroso/genética , Elementos Facilitadores Genéticos , Histonas/genética , Proteínas do Tecido Nervoso/genética , Neoplasias Ovarianas/genética , Alelos , Sítios de Ligação , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/patologia , Mapeamento Cromossômico , Proteínas Correpressoras/metabolismo , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/patologia , Feminino , Predisposição Genética para Doença , Genoma Humano , Estudo de Associação Genômica Ampla , Histonas/metabolismo , Humanos , Padrões de Herança , Proteínas do Tecido Nervoso/metabolismo , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Penetrância , Polimorfismo de Nucleotídeo Único , Risco
3.
PLoS One ; 15(5): e0232235, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401768

RESUMO

OBJECTIVE: Altered expression of caveolin-1 (CAV1) and autophagy marker ATG4C is observed in various types of human cancers. However, the clinical significance of CAV1 and ATG4C expression in epithelial ovarian cancer (EOC) remains largely unknown. The present study aims to explore the clinicopathological value and prognostic significance of CAV1 and ATG4C expression in EOC. METHODS: The expression pattern and prognostic value of CAV1 and ATG4C mRNA in EOC were analyzed using data from the Cancer Genome Atlas (TCGA) database (N = 373). In addition, immunohistochemistry analysis was performed to detect and assay the expression of CAV1 and ATG4C proteins in tissue microarray of EOC. RESULTS: Based on TCGA data, Kaplan-Meier analysis indicated that patients with low CAV1 mRNA (p = 0.021) and high ATG4C mRNA (p = 0.018) expression had a significantly shorter overall survival (OS). Cox regression analysis demonstrated that the expression levels of CAV1 (p = 0.023) and ATG4C mRNA (p = 0.040) were independent prognostic factors for OS in EOC. In addition, the Concordance Index of the nomogram for OS prediction was 0.660. Immunohistochemical analysis showed the expression levels of stromal CAV1 and cancerous ATG4C proteins, and high expression of both CAV1 and ATG4C protein in the stroma were found to significantly correlate with the histologic subtypes of EOC, especially with serous subtype. CONCLUSIONS: Decreased expression of CAV1 mRNA and increased expression of ATG4C mRNA in EOC can predict poor overall survival. The expression levels of CAV1 protein in stromal cells and ATG4C protein in cancer cells are significantly associated with histologic subtypes of EOC. These findings suggest that CAV1 and ATG4C serve as useful prognostic biomarkers and candidate therapeutic targets in EOC.


Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/patologia , Caveolina 1/metabolismo , Cisteína Endopeptidases/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/metabolismo , Prognóstico , Análise de Sobrevida , Adulto Jovem
4.
Obstet Gynecol ; 135(6): 1270-1274, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32459417

RESUMO

BACKGROUND: Women with germline BRCA1 or BRCA2 mutations have a lifetime risk of ovarian cancer of up to 46%. Opportunistic salpingectomy has been advocated as a risk-reducing strategy owing to increasing recognition of tubal origin, yet evidence of efficacy in this high-risk population is limited. CASE: This is the case of a woman with a BRCA1 mutation who underwent prophylactic mastectomy and bilateral salpingectomy with ovarian retention before the age of 40 years. She did not undergo oophorectomy and subsequently developed stage IV high-grade serous ovarian cancer 4 years after her initial surgery. CONCLUSION: More research is needed to determine the role of prophylactic salpingectomy with delayed oophorectomy, optimal timing of completion oophorectomy, and the risks and benefits compared with up-front risk-reducing salpingo-oophorectomy.


Assuntos
Carcinoma Epitelial do Ovário/diagnóstico , Genes BRCA1 , Neoplasias Ovarianas/diagnóstico , Adulto , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/cirurgia , Ensaios Clínicos como Assunto , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Mastectomia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/cirurgia , Ovariectomia , Salpingectomia , Tomografia Computadorizada por Raios X
5.
Arch Gynecol Obstet ; 301(5): 1219-1225, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32266526

RESUMO

OBJECTIVE: To determine the diagnostic value and clinical significance of serum HE4 levels in differentiating between benign and malignant ovarian disease in patients with elevated CA125 levels. METHODS: The levels and positive expression rate of HE4 were compared between 371 patients with elevated CA125 levels and benign ovarian disease, and 132 patients with epithelial ovarian cancer to determine the diagnostic value of HE4. RESULTS: The level and positive expression rate of HE4 differed significantly between the benign and malignant groups, in that, there was no significant difference in HE4 expression between CA125 low- and high-level groups within the benign ovarian disease group, with levels of HE4 being in the normal range in both groups. However, the positive expression rates and levels of HE4 in the malignant group were significantly different between the serum CA125 low- and high-level groups. ROC curve analysis showed that optimal HE4 cutoff values for increased accuracy in diagnosis were 78.03 pmol/L and 119.70 pmol/L before and after menopause, respectively. CONCLUSIONS: Serum HE4 levels can potentially be used as a marker to differentiate between benign and malignant ovarian disease with elevated serum CA125 levels. The high specificity of HE4 was superior in identifying benign ovarian disease. We recommend increasing the cutoff values of HE4 in premenopausal patients and decreasing the cutoff values in postmenopausal patients for increased accuracy in the differential diagnosis of patients with elevated CA125 levels.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Carcinoma Epitelial do Ovário/diagnóstico , Neoplasias Ovarianas/diagnóstico , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/metabolismo , Adulto , Biomarcadores Tumorais/análise , Carcinoma Epitelial do Ovário/sangue , Diagnóstico Diferencial , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Pré-Menopausa , Proteínas/análise , Proteínas/metabolismo , Curva ROC , Sensibilidade e Especificidade , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/análise
6.
Am J Clin Pathol ; 154(1): 103-114, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32271370

RESUMO

OBJECTIVES: High-grade serous carcinoma (HGSC) is the most common ovarian malignancy. The role of cytopathology in obtaining tissue diagnosis before institution of neoadjuvant chemotherapy (NACT) was evaluated. METHODS: All histopathology-proven HGSC specimens between 2015 and 2018 with prior cytopathologic diagnosis by ascitic fluid evaluation or fine-needle aspiration (FNA) of ovarian mass were reviewed with cell block immunocytochemistry for CK7, CK20, PAX8, WT1, and p53. RESULTS: Of 288 cases of HGSC, pre-NACT cytology diagnosis was established in 32% (93/288), with specific HGSC diagnoses made on ascitic fluid in 88% (82/93) and by ovarian mass FNA in 12% (11/93). The ascitic fluid showed moderate/high cellularity with papillary clusters in 76% (71/93) cases. Cell block immunocytochemistry showed tumor cells positive for CK7, PAX8, and WT1. p53 showed mutant or null-type positivity in 65% (33/51) and 33% (17/51) of cases, respectively, with 100% concordance with subsequent histopathology specimens. Poor/intermediate response to chemotherapy was shown in 75% of cases. CONCLUSIONS: Combined assessment of cytomorphology, cell block histomorphology, and ancillary immunohistochemical testing, including PAX8, WT1, and p53, allows for specific pre-NACT diagnoses of HGSC in ascitic fluid and ovarian FNA cytology. This practice allows for initiation of chemotherapy and diminution of disease burden prior to definitive surgical therapy.


Assuntos
Líquido Ascítico/patologia , Biomarcadores Tumorais/análise , Carcinoma Epitelial do Ovário/diagnóstico , Cistadenocarcinoma Seroso/diagnóstico , Citodiagnóstico/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Líquido Ascítico/química , Biópsia por Agulha Fina/métodos , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
7.
Artigo em Inglês | MEDLINE | ID: mdl-32273169

RESUMO

Ovarian cancer is the third most common gynaecological malignancy and the most lethal worldwide. Most patients are diagnosed with advanced disease which carries significant mortality. Improvements in treatment have only resulted in modest increases in survival. This has driven efforts to reduce mortality through screening. Multimodal ovarian cancer screening using a longitudinal CA125 algorithm has resulted in diagnosis at an earlier stage, both in average and high risk women in two large UK trials. However, no randomised controlled trial has demonstrated a definitive mortality benefit. Extended follow up is underway in the largest trial to date, UKCTOCS, to explore the delayed reduction in mortality that was noted. Meanwhile, screening is not currently recommended in the general population Some countries offer surveillance of high risk women. Novel screening modalities and longitudinal biomarker algorithms offer potential improvements to future screening strategies as does the development of better risk stratification tools.


Assuntos
Antígeno Ca-125/sangue , Carcinoma Epitelial do Ovário/diagnóstico , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Neoplasias Ovarianas/diagnóstico , Ovariectomia/métodos , Biomarcadores Tumorais/sangue , Carcinoma Epitelial do Ovário/sangue , Feminino , Humanos , Programas de Rastreamento/tendências , Neoplasias Ovarianas/sangue , Prognóstico , Fatores de Risco , Sensibilidade e Especificidade
8.
Best Pract Res Clin Obstet Gynaecol ; 65: 125-138, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32122773

RESUMO

As the treatment of epithelial ovarian cancer (OC) moves further into personalised medicine, the importance of determining the presence or absence of inherited mutations in cancer susceptibility genes has grown. It is now becoming routine to test for germline mutations in the BRCA1 and BRCA2 genes, which are responsible for a significant proportion of hereditary epithelial OC and are established predictive biomarkers of potential benefit from poly ADP ribose polymerase (PARP) inhibitors. The identification of patients with hereditary OC allows the patient to benefit from personalised treatment, while allowing family members to undergo cascade testing, where identification of unaffected carriers can allow early detection, risk-reduction or prevention for both breast and OC, and ultimately improve long-term outcomes. Other susceptibility genes, include the Lynch Syndrome (mismatch repair) genes and several other genes involved in the homologous recombination pathway (HRD genes), are implicated in OC genesis, and are also becoming of increasing interest as therapeutic options grow for these patients. This review will highlight the importance of the early detection of a germline gene pathogenic variant, which informs on the clinical course of disease in a particular patient, and therefore, guides therapeutic management including risk reducing and personalised treatment.


Assuntos
Carcinoma Epitelial do Ovário/genética , Predisposição Genética para Doença , Testes Genéticos/métodos , Neoplasias Ovarianas/genética , Carcinoma Epitelial do Ovário/diagnóstico , Feminino , Genes BRCA1 , Genes BRCA2 , Mutação em Linhagem Germinativa , Humanos , Neoplasias Ovarianas/diagnóstico
9.
Jpn J Clin Oncol ; 50(6): 643-652, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32211793

RESUMO

OBJECTIVE: Cyclase-associated actin cytoskeleton regulatory protein 2 (CAP2) regulates actin dynamics to control cell cycles and cell migration. CAP2 overexpression contributes to cancer progression in several tumor types; however, the role of CAP2 expression in ovarian cancer remains unclear. This study aimed to clarify the significance of CAP2 expression in epithelial ovarian tumor. METHODS: We evaluated CAP2 expression in ovarian cancer cell lines using quantitative real-time polymerase chain reaction, western blotting and immunocytochemistry and examined the effect of CAP2 silencing in migration and proliferation assays. CAP2 immunohistochemistry was conducted using tissue specimens from 432 ovarian carcinoma patients; a further 55 borderline and benign 65 lesions were analyzed. CAP2 expression levels were defined as low, intermediate or high, for correlation analysis with clinicopathological factors. RESULTS: CAP2 expression was significantly higher in cell lines from Type II ovarian cancer than in those in Type I, and knockdown of CAP2 showed decreased migration and proliferation. Higher levels of CAP2 expression in human tissues were associated with Type II histology, residual lesion, lymph node metastasis, ascites cytology and higher clinical stage. High CAP2 expression levels were observed in 26 (23.4%) of 111 Type II ovarian cancers and in 16 (5.0%) of 321 Type I cancers but not in any borderline or benign lesions. Multivariate analyses showed that CAP2 expression in ovarian cancer is an independent prognostic factor for recurrence-free survival (P = 0.019). CONCLUSION: CAP2 expression is upregulated in aggressive histologic types of epithelial ovarian cancer and serves as a novel prognostic biomarker for patient survival.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário/genética , Proteínas de Membrana/genética , Neoplasias Ovarianas/genética , Proteínas Adaptadoras de Transdução de Sinal/análise , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Proteínas de Membrana/análise , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Prognóstico , Intervalo Livre de Progressão , Regulação para Cima
10.
Sci Rep ; 10(1): 2213, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-32042020

RESUMO

Pre-operative discrimination of malignant masses is crucial for accurate diagnosis and prompt referral to a gynae oncology centre for optimal surgical intervention. HGSOC progression is correlated with local and systemic inflammation. We hypothesised that inclusion of inflammatory biomarkers in sera may improve diagnostic tests. In the training cohort, we tested four existing clinical tests (RMI score and ROMA, CA125 and HE4) and a panel of 28 immune soluble biomarkers in sera from 66 patients undergoing surgery for suspected ovarian cancer. Six promising immune biomarkers alone, or in combination with conventional tests, were subsequently analysed in an independent validation cohort (n = 69). IL-6 was identified as the main driver of variability followed closely by conventional diagnostic tests. Median sera IL-6 was higher in HGSOC patients compared to those with a benign mass or controls with normal ovaries (28.3 vs 7.3 vs 1.2 pg/ml, p < 0.0001). The combination of IL-6 further improved the overall predictive probability of the conventional tests. Modelling a two-step triage of women with a suspicious ovarian mass, with IL-6 > 3.75 pg/ml as primary triage followed by conventional tests (CA125 or RMI score) identified ovarian cancer in patients with a misclassification rate of 4.54-3.03%, superior to the use of CA125 or RMI alone (9.09 to 10.60). The validation cohort demonstrated a similar improvement in the diagnostic sensitivity following addition of IL-6. IL-6 in combination with conventional tests may be a useful clinical biomarker for triage of patients with a suspected malignant ovarian mass.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Epitelial do Ovário/diagnóstico , Interleucina-6/sangue , Neoplasias Ovarianas/diagnóstico , Triagem/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Ovariectomia , Ovário/patologia , Ovário/cirurgia , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico
11.
J Ovarian Res ; 13(1): 17, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32050995

RESUMO

OBJECTIVE: The aim of this study is to establish a noninvasive preoperative model for predicting primary optimal cytoreduction in advanced epithelial ovarian cancer by HE4 and CA125 combined with clinicopathological parameters. METHODS: Clinical data including preoperative serum HE4 and CA125 level of 83 patients with advanced epithelial ovarian cancer were collected. The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of each clinical parameter were calculated. The Predictive Index score model and the logistic model were constructed to predict the primary optimal cytoreduction. RESULTS: Optimal surgical cytoreduction was achieved in 62.65% (52/83) patients. Cutoff values of preoperative serum HE4 and CA125 were 777.10 pmol/L and 313.60 U/ml. (1) Patients with PIV ≥ 6 may not be able to achieve optimal surgical cytoreduction. The diagnostic accuracy, NPV, PPV and specificity for diagnosing suboptimal cytoreduction were 71, 100, 68, and 100%, respectively. (2) The logistic model was: logit p = 0.12 age - 2.38 preoperative serum CA125 level - 1.86 preoperative serum HE4 level-2.74 histological type-3.37. AUC of the logistic model in the validation group was 0.71(95%CI 0.54-0.88, P = 0.025). Sensitivity and specificity were 1.00 and 0.44, respectively. CONCLUSION: Age, preoperative serum CA125 level and preoperative serum HE4 level are important non-invasive predictors of primary optimal surgical cytoreduction in advanced epithelial ovarian cancer. Our PIV and logistic model can be used for assessment before expensive and complex predictive methods including laparoscopy and diagnostic imaging. Further future clinical validation is needed.


Assuntos
Antígeno Ca-125/sangue , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/cirurgia , Proteínas de Membrana/sangue , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/cirurgia , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/metabolismo , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/patologia , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Modelos Estatísticos , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Resultado do Tratamento
12.
Indian J Pathol Microbiol ; 63(Supplement): S64-S69, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32108633

RESUMO

In spite of the advent of many high throughput technologies, tumor tissue biomarkers are still the gold standard for diagnosis and prognosis of different malignancies including epithelial ovarian cancer (EOC). EOC is a heterogeneous disease comprised of five major subtypes which show distinct clinicopathological features and therapy response. Acquirement of chemoresistance toward therapy is a major challenge for successful treatment outcome in EOC patients. Several markers have been tested by immunohistochemical method to evaluate their prognostic merit to predict clinical outcome. However, a vast majority of such markers have been assessed for high-grade serous and clear cell ovarian cancer, among all subtypes of EOC. The current review elaborates upon those biomarkers that can potentially predict chemoresistance with subtype specificity.


Assuntos
Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário/classificação , Progressão da Doença , Feminino , Humanos , Ovário/patologia , Prognóstico
13.
PLoS One ; 15(1): e0227707, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31917801

RESUMO

Epithelial ovarian cancer (OC) is the most deadly cancer of the female reproductive system. To date, there is no effective screening method for early detection of OC and current diagnostic armamentarium may include sonographic grading of the tumor and analyzing serum levels of tumor markers, Cancer Antigen 125 (CA-125) and Human epididymis protein 4 (HE4). Microorganisms (bacterial, archaeal, and fungal cells) residing in mucosal tissues including the gastrointestinal and urogenital tracts can be altered by different disease states, and these shifts in microbial dynamics may help to diagnose disease states. We hypothesized that the peritoneal microbial environment was altered in patients with OC and that inclusion of selected peritoneal microbial features with current clinical features into prediction analyses will improve detection accuracy of patients with OC. Blood and peritoneal fluid were collected from consented patients that had sonography confirmed adnexal masses and were being seen at SIU School of Medicine Simmons Cancer Institute. Blood was processed and serum HE4 and CA-125 were measured. Peritoneal fluid was collected at the time of surgery and processed for Next Generation Sequencing (NGS) using 16S V4 exon bacterial primers and bioinformatics analyses. We found that patients with OC had a unique peritoneal microbial profile compared to patients with a benign mass. Using ensemble modeling and machine learning pathways, we identified 18 microbial features that were highly specific to OC pathology. Prediction analyses confirmed that inclusion of microbial features with serum tumor marker levels and control features (patient age and BMI) improved diagnostic accuracy compared to currently used models. We conclude that OC pathogenesis alters the peritoneal microbial environment and that these unique microbial features are important for accurate diagnosis of OC. Our study warrants further analyses of the importance of microbial features in regards to oncological diagnostics and possible prognostic and interventional medicine.


Assuntos
Líquido Ascítico/microbiologia , Antígeno Ca-125/sangue , Carcinoma Epitelial do Ovário/diagnóstico , Proteínas de Membrana/sangue , Microbiota/genética , Neoplasias Ovarianas/diagnóstico , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/análise , Idoso , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/microbiologia , Carcinoma Epitelial do Ovário/cirurgia , Estudos Transversais , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Feminino , Humanos , Histerectomia , Laparoscopia , Aprendizado de Máquina , Pessoa de Meia-Idade , Modelos Biológicos , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/microbiologia , Neoplasias Ovarianas/cirurgia , Ovariectomia , Projetos Piloto , Período Pré-Operatório , Prognóstico , RNA Ribossômico 16S/genética
14.
Cancer Res ; 80(6): 1357-1367, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31969373

RESUMO

Ovarian cancer has few known risk factors, hampering identification of high-risk women. We assessed the association of prediagnostic plasma metabolites (N = 420) with risk of epithelial ovarian cancer, including both borderline and invasive tumors. A total of 252 cases and 252 matched controls from the Nurses' Health Studies were included. Multivariable logistic regression was used to estimate ORs and 95% confidence intervals (CI), comparing the 90th-10th percentile in metabolite levels, using the permutation-based Westfall and Young approach to account for testing multiple correlated hypotheses. Weighted gene coexpression network analysis (WGCNA; n = 10 metabolite modules) and metabolite set enrichment analysis (n = 23 metabolite classes) were also evaluated. An increase in pseudouridine levels from the 10th to the 90th percentile was associated with a 2.5-fold increased risk of overall ovarian cancer (OR = 2.56; 95% CI, 1.48-4.45; P = 0.001/adjusted P = 0.15); a similar risk estimate was observed for serous/poorly differentiated tumors (n = 176 cases; comparable OR = 2.38; 95% CI, 1.33-4.32; P = 0.004/adjusted P = 0.55). For nonserous tumors (n = 34 cases), pseudouridine and C36:2 phosphatidylcholine plasmalogen had the strongest statistical associations (OR = 9.84; 95% CI, 2.89-37.82; P < 0.001/adjusted P = 0.07; and OR = 0.11; 95% CI, 0.03-0.35; P < 0.001/adjusted P = 0.06, respectively). Five WGCNA modules and 9 classes were associated with risk overall at FDR ≤ 0.20. Triacylglycerols (TAG) showed heterogeneity by tumor aggressiveness (case-only heterogeneity P < 0.0001). The TAG association with risk overall and serous tumors differed by acyl carbon content and saturation. In summary, this study suggests that pseudouridine may be a novel risk factor for ovarian cancer and that TAGs may also be important, particularly for rapidly fatal tumors, with associations differing by structural features. SIGNIFICANCE: Pseudouridine represents a potential novel risk factor for ovarian cancer and triglycerides may be important particularly in rapidly fatal ovarian tumors.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Epitelial do Ovário/epidemiologia , Neoplasias Ovarianas/epidemiologia , Pseudouridina/sangue , Triglicerídeos/sangue , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/metabolismo , Estudos de Casos e Controles , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Metabolômica , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/metabolismo , Estudos Prospectivos , Pseudouridina/metabolismo , Medição de Risco/métodos , Fatores de Risco , Triglicerídeos/metabolismo
15.
Int J Clin Oncol ; 25(1): 51-58, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31473885

RESUMO

BACKGROUND: Endometriosis is a risk factor for ovarian cancer. Endometriosis-associated ovarian cancer (EAOC), most commonly clear cell carcinoma, is believed to develop from ovarian endometrial cysts. In this study, we reviewed published cases of EAOC considered to have developed from endometrial cysts, and focused on the observation period. METHODS: We searched for articles published since January 2000 that reported cases of ovarian cancer thought to have originated from endometrial cysts using PubMed, Web of Science, and Ichushi-Web. The period from the start of follow-up of the endometrial cyst to the diagnosis of ovarian cancer was calculated. RESULTS: Seventy-nine cases were identified from 32 articles. The median period from the diagnosis of endometrial cysts to the diagnosis of ovarian cancer was only 36 months. Approximately 75% of cases developed into cancer within 60 months and most cases developed within 120 months. CONCLUSION: Our results suggest that clinically detectable cysts subsequently diagnosed as ovarian cancer might already have contained cancer cells. Therefore, the mechanism of EAOC development needs to be re-examined and appropriate management guidelines need to be developed.


Assuntos
Carcinoma Endometrioide/etiologia , Carcinoma Epitelial do Ovário/etiologia , Endometriose/complicações , Cistos Ovarianos/complicações , Neoplasias Ovarianas/etiologia , Adulto , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/patologia , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/patologia , Endometriose/diagnóstico , Endometriose/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Cistos Ovarianos/diagnóstico , Cistos Ovarianos/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia
16.
Support Care Cancer ; 28(1): 73-78, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30980260

RESUMO

BACKGROUND: The aim of this study was to analyze the potential impact of chemotherapy-induced nausea and vomiting (CINV) on dose reductions, discontinuation of chemotherapy, and survival. PATIENTS AND METHODS: This study was designed as individual participant data meta-analysis with the original study data of three phase II/III trials that were conducted by the North-Eastern German Society of Gynecological Oncology (NOGGO) including 1213 patients with recurrent ovarian cancer. Logistic and Cox regression analyses were used to estimate odds and hazard ratios after adjusting for age, ECOG, amount of delivered cycles, amount of recurrences, and amount of comedications and study. RESULTS: The majority of patients developed nausea (58.1%) and almost one third experienced vomiting (31.0%). CINV was not associated with FIGO stage, grading, histology, and number of recurrences. The necessity of dose reduction and discontinuation of chemotherapy did not correlate to nausea and vomiting (p = 0.88, p = 0.39 and p = 0.25, p = 0.54 respectively). Progression-free survival was shorter in patients with grade III/IV nausea and vomiting (p = 0.02; hazard ratio (HR) for grade III/IV nausea 1.58, 95% CI 1.14-2.20, and p = 0.02; HR for grade III/IV vomiting 1.67, 95% CI 1.15-2.42 respectively). CINV grade III/IV was also associated with poorer overall survival (p < 0.001; HR for grade III/IV nausea 2.35, 95% CI 1.64-3.37, and p < 0.001; HR for grade III/IV vomiting 1.67, 95% CI 1.15-2.42 respectively). CONCLUSION: CINV is significantly associated with poorer prognosis in recurrent ovarian cancer patients while there was no correlation found with the necessity of dose reduction and prior discontinuation of treatment. This study underlines the importance of prevention and treatment of CINV as part of early best supportive care.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Náusea/diagnóstico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Vômito/diagnóstico , Adulto , Idoso , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/patologia , Ensaios Clínicos Fase II como Assunto/estatística & dados numéricos , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Resultado do Tratamento , Vômito/induzido quimicamente
17.
Cancer Causes Control ; 31(1): 25-31, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31673820

RESUMO

PURPOSE: The importance of benign ovarian tumors as precursors or risk markers for ovarian cancer is not fully understood. Studies on the association between benign ovarian tumors and ovarian cancer have provided inconclusive results. We examined the overall and histological type-specific risk of ovarian cancer among 158,221 Danish women diagnosed with a benign ovarian tumor during 1978-2016. METHODS: The study cohort was linked to the Danish Cancer Register to identify all cases of epithelial ovarian cancer, and standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated. RESULTS: After excluding the first year of follow-up, women with benign ovarian tumors did not have an increased risk for overall epithelial ovarian cancer (SIR 1.02; 95% CI 0.93-1.11), as compared with women in the general population. However, we found an increased risk for mucinous ovarian cancer (SIR 2.06; 95% CI 1.67-2.52); both solid and cystic benign ovarian tumors were associated with an increased risk. The risk for mucinous ovarian cancer was increased irrespective of the age at benign ovarian tumors diagnosis and persisted for up to 20 years after the benign ovarian tumor diagnosis. No clear associations for other histological types of ovarian cancer were observed, except for an increased risk for serous ovarian cancer among women diagnosed with benign ovarian tumors at an young age. CONCLUSIONS: Benign ovarian tumors may be associated with long-term increased risk for mucinous ovarian cancer.


Assuntos
Carcinoma Epitelial do Ovário/complicações , Carcinoma Epitelial do Ovário/diagnóstico , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/diagnóstico , Adulto , Idoso , Carcinoma Epitelial do Ovário/epidemiologia , Cistadenocarcinoma Seroso/complicações , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/epidemiologia , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Neoplasias Ovarianas/epidemiologia , Fatores de Risco , Adulto Jovem
18.
Virchows Arch ; 476(2): 195-207, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31797087

RESUMO

Germline/somatic BRCA-mutated ovarian carcinomas (OC) are associated to have better response with platinum-based chemotherapy and long-term prognosis than non-BRCA-associated OCs. In addition, these mutations are predictive factors to response to Poly(ADP-ribose) polymerase (PARP) inhibitors. Different positioning papers have addressed the clinical recommendations for BRCA testing in OC. This consensus guide represents a collection of technical recommendations to address the detection of BRCA1/2 mutations in the molecular diagnostic testing strategy for OC. Under the coordination of Spanish Society of Pathology (SEAP-IAP) and the Spanish Society of Human Genetics (AEGH), these recommendations have been developed by pathologists and geneticists taking into account previously published recommendations and their experience in the molecular characterization of these genes. Since the implementation of BRCA testing as a predictive factor can initiate the workflow by testing germline mutations in the blood or by testing both germline and somatic mutations in tumor tissue, distinctive features of both strategies are discussed. Additionally, the recommendations included in this paper provide some references, quality parameters, and genomic tools aimed to standardize and facilitate the clinical genomic diagnosis of OC.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial do Ovário/genética , Detecção Precoce de Câncer , Mutação/genética , Carcinoma Epitelial do Ovário/diagnóstico , Consenso , Detecção Precoce de Câncer/métodos , Feminino , Humanos
19.
Am J Obstet Gynecol ; 222(1): 56.e1-56.e17, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31351062

RESUMO

BACKGROUND: Transvaginal ultrasound and serum CA125 are routinely used for differential diagnosis of pelvic adnexal mass. Use of human epididymis 4 was approved in the United States in 2011. However, there is scarcity of studies evaluating the additional value of human epididymis 4. OBJECTIVE: The objective of the study was to evaluate the performance characteristics of transvaginal ultrasound, CA125, and human epididymis 4 for differential diagnosis of ovarian cancer in postmenopausal women with adnexal masses. STUDY DESIGN: This was a cohort study nested within the screen arms of the multicenter randomized controlled trial, United Kingdom Collaborative Trial of Ovarian Cancer Screening, based in England, Wales, and Northern Ireland. In United Kingdom Collaborative Trial of Ovarian Cancer Screening, 48,230 women randomized to transvaginal ultrasound screening and 50,078 to multimodal screening (serum CA125 interpreted by Risk of Ovarian Cancer Algorithm with second line transvaginal ultrasound) underwent the first (prevalence) screen. Women with adnexal lesions and/or persistently elevated risk were clinically assessed and underwent surgery or follow-up for a median of 10.9 years. Banked samples taken within 6 months of transvaginal ultrasound from all clinically assessed women were assayed for human epididymis 4 and CA125. Area under the curve and sensitivity for diagnosing ovarian cancer of multiple penalized logistic regression models incorporating logCA125, log human epididymis 4, age, and simple ultrasound features of the adnexal mass were compared. RESULTS: Of 1590 (158 multimodal, 1432 ultrasound) women with adnexal masses, 78 were diagnosed with ovarian cancer (48 invasive epithelial ovarian, 14 type I, 34 type II; 24 borderline epithelial; 6 nonepithelial) within 1 year of scan. The area under the curve (0.893 vs 0.896; P = .453) and sensitivity (74.4% vs 75.6% ;P = .564) at fixed specificity of 90% of the model incorporating age, ultrasound, and CA125 were similar to that also including human epididymis 4. Both models had high sensitivity for invasive epithelial ovarian (89.6%) and type II (>91%) cancers. CONCLUSION: Our population cohort study suggests that human epididymis 4 adds little value to concurrent use of CA125 and transvaginal ultrasound in the differential diagnosis of adnexal masses in postmenopausal women.


Assuntos
Antígeno Ca-125/metabolismo , Carcinoma Epitelial do Ovário/diagnóstico , Proteínas de Membrana/metabolismo , Neoplasias Ovarianas/diagnóstico , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/metabolismo , Idoso , Carcinoma Epitelial do Ovário/diagnóstico por imagem , Carcinoma Epitelial do Ovário/metabolismo , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/metabolismo , Pós-Menopausa , Ensaios Clínicos Controlados Aleatórios como Assunto , Sensibilidade e Especificidade , Ultrassonografia
20.
Asian Pac J Cancer Prev ; 20(12): 3603-3609, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31870100

RESUMO

BACKGROUND: Ovarian cancer is the seventh most common cancer in females with the highest mortality rate of all gynecological cancers due to its late discovery and ambiguous symptoms. Thus, there is a need for new promising strategies to diagnose ovarian cancer. We aimed at finding a characteristic plasma proteome pattern that could be used for the detection of epithelial ovarian cancer, in comparison with benign ovarian masses and healthy controls. We also aimed at differentiating between profiling of plasma proteins in early and advanced stages of ovarian cancer and between serous and non-serous histopathological types. METHODS: The combination of MagSi-proteomics C8 beads, Ultraflextreme MALDI-TOF and ClinPro Tools software was used to compare the plasma protein spectra from 50 patients with epithelial ovarian cancer, 20 patients with benign ovarian masses and 50 age matched healthy females. RESULTS: A plasma proteome profile of 21 peaks differentiated patients with epithelial ovarian cancer from healthy controls with a sensitivity of 73 % and a specificity of 82.8% upon external validation, while a 5-peak profile differentiated patients with epithelial ovarian cancer from patients with benign ovarian masses with a sensitivity of 81% and a specificity of 73.7%. A 20 peak profile was generated to discriminate between early and late stages of the disease with 88.3% recognition capability and 70% cross validation. CONCLUSION: MALDI-TOF proteomic profiling represents a promising potential tool for diagnosing epithelial ovarian cancer, discriminating between early and advanced stages and between serous and non- serous types.


Assuntos
Carcinoma Epitelial do Ovário/diagnóstico , Perfilação da Expressão Gênica/métodos , Neoplasias Ovarianas/diagnóstico , Proteoma/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Proteínas Sanguíneas/análise , Carcinoma Epitelial do Ovário/patologia , Egito , Feminino , Humanos , Separação Imunomagnética/métodos , Neoplasias Ovarianas/patologia , Albumina Sérica/química
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