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1.
BMC Cancer ; 21(1): 220, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663405

RESUMO

BACKGROUND: High grade serous ovarian cancer (HGSOC) accounts for nearly 60% of total cases of epithelial ovarian cancer. It is the most aggressive subtype, which shows poor prognosis and low patient survival. For better management of HGSOC patients, new prognostic biomarkers are required to facilitate improved treatment strategies and ensure suitable healthcare decisions. METHODS: We performed genome wide expression analysis of HGSOC patient samples to identify differentially expressed genes (DEGs) using R based Limma package, Clust and other statistical tools. The identified DEGs were subjected to weighted gene co-expression network analysis (WGCNA) to identify co-expression patterns of relevant genes. Module trait and gene ontology analyses were performed to establish important gene co-expression networks and their biological functions. Overlapping the most relevant DEG cluster 4 with prominent WGCNA cyan module identified strongest correlation of UBE2Q1 with ovarian cancer and its prognostic significance on survival probability of ovarian cancer patients was investigated. The predictive value of UBE2Q1 as a potential biomarker was analysed by correlating its expression with 12-months relapse free survival of patients in response to platin/taxane, the standard first-line chemotherapy for ovarian cancer, and analysing area under the ROC curve. RESULTS: An integrated gene expression analysis and WGCNA, identified UBE2Q1 as a potential prognostic marker associated with poor relapse-free survival and response outcome to platin/taxane treatment of patients with high grade serous ovarian cancer. CONCLUSIONS: Our study identifies a potential UBE2Q1 - B4GALT3 functional axis in ovarian cancer, where only the E2 conjugating enzyme showed a poor prognostic impact on the disease.


Assuntos
Biologia Computacional/métodos , Cistadenocarcinoma Seroso/mortalidade , Neoplasias Ovarianas/mortalidade , Enzimas de Conjugação de Ubiquitina/genética , Neoplasias da Mama/mortalidade , Feminino , Galactosiltransferases/genética , Galactosiltransferases/fisiologia , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Prognóstico , Enzimas de Conjugação de Ubiquitina/fisiologia
2.
Anticancer Res ; 41(3): 1647-1654, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788761

RESUMO

BACKGROUND: Ovarian high-grade serous carcinoma (HGSC) gradually acquires chemoresistance after recurrence. Our previous study on ovarian clear-cell carcinoma found histone deacetylase 6 (HDAC6) overexpression led to chemoresistance. This study aimed to evaluate HDAC6 as a predictor of chemoresistance and a therapeutic target for ovarian HGSC. PATIENTS AND METHODS: The clinical significance of HDAC6 as a predictor of prognosis and chemoresistance in HGSC was immunohistochemically evaluated. In addition, expression of programmed cell death ligand-1 (PD-L1), and hypoxia-inducible factor-1α (HIF1α) were analyzed using clinical samples from 88 patients with ovarian HGSC, and their clinicopathological characteristics were reviewed. RESULTS: Twenty-three patients had high HDAC6 expression, 10 positive PD-L1 expression, and 33 high HIF-1α expression. HDAC6 up-regulation was correlated with not undergoing interval debulking surgery (p<0.001), incomplete surgical resection (p=0.002), and frequent occurrence of stable disease/progressive disease according to the Response Evaluation Criteria in Solid Tumors (p=0.005) criteria. On Kaplan-Meier analysis, high HDAC6 expression was significantly associated with reduced progression-free (p=0.001) and overall (p=0.008) survival. On multivariate analysis, high HDAC6 expression (hazard ratio=1.65, 95% confidence interval 1.03-2.66; p=0.039) and surgery status were independent prognostic factors of progression-free survival. PD-L1 and HIF1α expression positively correlated with that of HDAC6. CONCLUSION: HDAC6 may become a potential therapeutic target in patients with ovarian HGSC since its up-regulation is considered to be associated with a poor prognosis in patients with this cancer.


Assuntos
Cistadenocarcinoma Seroso/tratamento farmacológico , Desacetilase 6 de Histona/fisiologia , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/cirurgia , Resistencia a Medicamentos Antineoplásicos , Feminino , Desacetilase 6 de Histona/antagonistas & inibidores , Desacetilase 6 de Histona/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Prognóstico , Regulação para Cima
3.
Zhonghua Fu Chan Ke Za Zhi ; 55(12): 848-856, 2020 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-33355760

RESUMO

Objective: To investigate the diagnosis, treatment and prognosis of uterine serous carcinoma (USC), and further analyze the prognostic factors. Methods: USC patients who underwent surgery with complete follow-up at Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences between January 1, 2004 and December 31, 2014 were retrospectively reviewed. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results: (1) Diagnosis and treatment: the study included 71 USC patients. Only 32 patients (45%, 32/71) were diagnosed preoperatively with USC, and 25 cases of them (35%, 25/71) underwent USC standard comprehensive staging surgery. Of the 25 patients, 10 cases (40%, 10/25) had up-staged after operation. (2) Prognosis: the 5-year disease free survival (DFS) rate and overall survival (OS) rate for all patients were 76.5% and 80.6%, respectively. (3) The results of prognostic factors analysis: univariate analysis on age, range of lymphadenectomy, peritoneal cytology, the depth of myometrial invasion, adnexal and (or) serosa involvement and omentum metastasis were significantly associated with 5-year DFS rate (all P<0.05); range of lymphadenectomy, range of surgical staging, peritoneal cytology, adnexal and (or) serosa involvement and postoperative adjuvant treatment were significantly associated with 5-year OS rate (all P<0.05). Multivariate analysis on range of surgical staging (HR=5.18, 95%CI: 1.04-25.70, P=0.044) and adnexal and (or) serosa involvement (HR=8.41, 95%CI: 2.28-31.05, P=0.001) were independent prognostic factors for 5-year DFS rate; range of lymphadenectomy [no lymphadenectomy vs pelvic lymphadenectomy (PLN)+para-aortic lymphadenectomy (PALN), HR=27.76, 95%CI: 1.76-437.78, P=0.018;PLN vs PLN+PALN, HR=5.98, 95%CI: 1.11-32.27, P=0.038] and peritoneal cytology (HR=5.47, 95%CI: 1.18-25.39, P=0.030) were independent prognostic factors for 5-year OS rate. Conclusions: The preoperative pathological diagnosis of USC is difficult, resulting in incomplete surgical staging and inaccurate staging. Range of surgical staging, adnexal and (or) serosa involvement, peritoneal cytology and range of lymphadenectomy are independent prognostic factors, which deserve much attention in clinical practice.


Assuntos
Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/terapia , Procedimentos Cirúrgicos em Ginecologia/métodos , Terapia Neoadjuvante/métodos , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/cirurgia , China/epidemiologia , Cistadenocarcinoma Seroso/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Cuidados Pós-Operatórios , Prognóstico , Estudos Retrospectivos , Neoplasias Uterinas/mortalidade
4.
Sci Rep ; 10(1): 2757, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066851

RESUMO

Homologous recombination repair (HRR) pathway deficiency (HRD) is involved in the tumorigenesis and progression of high-grade serous ovarian carcinoma (HGSOC) as well as in the sensitivity to platinum chemotherapy drugs. In this study, we obtained data from The Cancer Genome Atlas (TCGA) on HGSOC and identified scores for the loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions, and calculated the HRD score. We then investigated the relationships among the score, genetic/epigenetic alterations in HRR-related genes, and the clinical data. We found that BRCA1/2 mutations were enriched in the group with HRD scores ≥63. Compared with the groups with scores ≤62, this group had a good prognosis; we thus considered HRD scores ≥63 to be the best cutoff point for identifying HRD cases in HGSOC. Classification of HGSOC cases by the HRD status revealed a better prognosis for HRD cases caused by genetic alterations (genetic HRD) than those caused by epigenetic changes and those caused by undetermined reasons (p = 0.0002). Among cases without macroscopic residual tumors after primary debulking surgery, 11 of 12 genetic HRD cases survived after the median observation period of 6.6 years, showing remarkably high survival rates (p = 0.0059). In conclusion, HGSOC can be classified into subtypes with different prognoses according to HRD status. This classification could be useful for personalized HGSOC treatment.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Cistadenocarcinoma Seroso/diagnóstico , DNA de Neoplasias/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/diagnóstico , Reparo de DNA por Recombinação , Desequilíbrio Alélico , Atlas como Assunto , Proteína BRCA1/metabolismo , Proteína BRCA2/metabolismo , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/cirurgia , DNA de Neoplasias/metabolismo , Epigênese Genética , Feminino , Humanos , Perda de Heterozigosidade , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Medicina de Precisão , Prognóstico , Análise de Sobrevida , Terminologia como Assunto
5.
Reprod Sci ; 27(1): 194-203, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32046381

RESUMO

Tumor-associated macrophages and tumor-infiltrating lymphocytes are associated with survival in solid malignancies. Given the physiological link to peripheral immune cell counts, we evaluated if peripheral immune cell counts were predictors of outcomes in endometrial cancer. A retrospective study was completed for endometrial cancer cases between 2000 and 2010. Kaplan-Meier, bivariate, and multivariable Cox proportion hazard analyses were performed examining the relations between survival and peripheral immune cell counts. Three hundred ten patients were identified. In bivariate analyses, high monocyte counts (> 0.7 × 109 cells/L) trended with decreased progression free survival (PFS) (p = 0.10) and poorer overall survival (OS) (p = 0.16). By contrast, high lymphocyte level (> 1.5 × 109 cells/L) was associated with improved PFS (p = 0.008) and OS (p = 0.006). These findings were consistent for type I and type II endometrial cancers. In a multivariable Cox model, high monocyte level was associated with a greater risk of disease recurrence (hazard ratio (HR) = 1.63, p < 0.035). Other significant predictors of recurrence were age, non-endometrioid histology, and the presence of lymph vascular space invasion (LVSI). In a multivariable Cox model, high lymphocyte count trended with a lower risk of death (HR = 0.66, p = 0.07). Age, surgical stage, non-endometrioid histology, and LVSI were also associated with death in this model. In this sample of endometrial cancer patients, we found that high preoperative lymphocyte counts were associated with improved overall improved survival. High monocyte counts were associated with poorer disease-free survival outcomes. Further studies that focused on understanding tumor-antagonizing and pro-tumoral effects of lymphocytes and monocytes, respectively, in endometrial cancer are recommended.


Assuntos
Carcinoma Endometrioide/sangue , Cistadenocarcinoma Seroso/sangue , Neoplasias do Endométrio/sangue , Linfócitos , Monócitos , Idoso , Biomarcadores/sangue , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/cirurgia , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/cirurgia , Intervalo Livre de Doença , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Contagem de Leucócitos , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Sistema de Registros , Estudos Retrospectivos
6.
Gynecol Oncol ; 157(2): 340-347, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32067813

RESUMO

OBJECTIVES: To develop a transcriptomic signature capable of predicting overall survival (OS) for uterine serous carcinoma (USC). METHODS: RNAseq data for 58 USC patients were obtained from TCGA. Expression of 73 candidate genes was measured for 67 Augusta University (AU) samples using NanoString technology. RESULTS: Analysis of the TCGA RNAseq data identified 73 genes that individually predict prognosis for USC patients and an elastic net model with all 73 genes (USC73) distinguishes a good OS group with low USC73 score from a poor OS group with high USC73 score (5-year OS = 83.3% and 13.3% respectively, HR = 40.1; p = 3 × 10-8). This finding was validated in the independent AU cohort (HR = 4.3; p = 0.0004). The poor prognosis group with high USC73 score consists of 37.9% and 32.8% of patients in the TCGA and AU cohort respectively. USC73 score and pathologic stage independently contribute to OS and together provide the best prognostic value. Early stage, low USC73 patients have the best prognosis (5-year OS = 85.1% in the combined dataset), while advanced stage, high USC73 patients have the worst prognosis (5-year OS = 6.4%, HR = 30.5, p = 1.2 × 10-12). Consistent with the observed poor survival, primary cell cultures from high USC73 patients had higher proliferation rate and cell cycle progression; and high USC73 patients had lower rates of complete response to standard therapy. CONCLUSIONS: The USC73 transcriptomic signature and stage independently predict OS of USC patients and the best prediction is achieved using USC73 and stage. USC73 may also serve as a therapeutic biomarker to guide patient care.


Assuntos
Cistadenocarcinoma Seroso/genética , Neoplasias Uterinas/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/terapia , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Análise de Sequência de RNA , Análise Serial de Tecidos , Transcriptoma , Células Tumorais Cultivadas , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapia
7.
Cancer Immunol Immunother ; 69(2): 175-187, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31853576

RESUMO

High grade ovarian serous cancer (HGSC) is a malignant disease with high mortality. Glycosylation plays important roles in tumor invasion and immune evasion, but its effect on the immune microenvironment of HGSC remains unclear. This study examined the association of glycosyltransferase expression with HGSC prognosis and explored the underlying mechanism using clinical specimens and integrated bioinformatic analyses. We identified a cluster of 15 glycogenes associated with reduced overall survival, and GALNT10 was found to be an independent predictor of HGSC prognosis. The high GALNT10 expression was associated with increased regulatory CD4+ T cells infiltration and decreased granzyme B expression in CD8+ T cells. The expression of GALNT10 and its product, Tn antigen, in HGSC specimens was associated with the increased infiltration of M2 macrophages and neutrophils, and the decreased infiltration of CD3+ T cells, NK cells, and B cells. Taken collectively, high GALNT10 expression confers with immunosuppressive microenvironment to promote tumor progression and predicts poor clinical outcomes in HGSC patients.


Assuntos
Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/mortalidade , Expressão Gênica , N-Acetilgalactosaminiltransferases/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Microambiente Tumoral/genética , Biomarcadores Tumorais , Biologia Computacional/métodos , Cistadenocarcinoma Seroso/patologia , Bases de Dados Genéticas , Feminino , Humanos , Imuno-Histoquímica , Imunomodulação/genética , Gradação de Tumores , Neoplasias Ovarianas/patologia , Prognóstico , Estudos Retrospectivos
8.
In Vivo ; 34(1): 177-184, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882477

RESUMO

BACKGROUND: Epithelial ovarian cancer (EOC) is the major gynecological cause of cancer deaths. Annexin A1 (ANXA1) protein has been implicated in the aggressiveness of several cancer types. MATERIALS AND METHODS: This study retrospectively assessed ANXA1 expression in epithelial cells of 156 pre-chemotherapy EOC samples and 34 normal ovarian samples from patients treated at Salah Azaiez Institute. Using immunohistochemistry, ANXA1 expression was compared in normal versus cancer samples; correlations with clinicopathological features, including overall survival, were sought. RESULTS: Fifty-two percent of tumor samples showed epithelial ANXA1 staining versus only 26% of normal samples (Fisher's exact test, p=0.00794). Epithelial ANXA1 expression was correlated with better overall survival in both univariate and multivariate analyses. CONCLUSION: The possible contribution of ANXA1 overexpression to EOC outcome may be relevant to therapeutic strategies.


Assuntos
Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma Mucinoso/mortalidade , Anexina A1/metabolismo , Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/mortalidade , Neoplasias do Endométrio/mortalidade , Neoplasias Ovarianas/mortalidade , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/terapia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/terapia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
9.
Gynecol Oncol ; 156(1): 70-76, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31739992

RESUMO

OBJECTIVES: The objective of our study was to assess survival among patients with uterine serous carcinoma (USC) undergoing sentinel lymph node (SLN) mapping alone versus patients undergoing systematic lymphadenectomy (LND). METHODS: We retrospectively reviewed patients undergoing primary surgical treatment for newly diagnosed USC at our institution from 1/1/1996-12/31/2017. Patients were assigned to either SLN mapping alone (SLN cohort) or systematic LND without SLN mapping (LND cohort). Progression-free (PFS) and overall survival (OS) were estimated using Kaplan-Meier method, compared using Logrank test. RESULTS: 245 patients were available for analysis: 79 (32.2%) underwent SLN, 166 (67.7%) LND. 132 (79.5%) in the LND cohort had paraaortic LND (PALND) versus none in the SLN cohort. Median age: 66 and 68 years in the SLN and LND cohorts, respectively (p>0.05). Proportion of stage I/II disease: 67.1% (n = 53) and 64.5% (n = 107) in the SLN and LND cohorts, respectively (p>0.05). Median follow-up: 23 (range, 1-96) and 66 months (range, 4-265) in the SLN and LND cohorts, respectively (p < 0.001). Two-year OS in stage I/II disease (n = 160, 60.1%): 96.6% (SE ± 3.4) and 89.6% (SE ± 2.2) in the SLN and LND cohorts, respectively (p = 0.8). Two-year OS in stage III disease (n = 77): 73.6% (SE ± 10.2) and 77.3% (SE ± 5.8) in the SLN and LND cohorts, respectively (p = 0.8). CONCLUSIONS: SLN mapping alone and systematic LND yielded similar survival outcomes in stage I-III USC. In our practice, the SLN algorithm has replaced systematic LND as the primary staging modality in this setting.


Assuntos
Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Linfonodo Sentinela/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/mortalidade , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/métodos , Análise de Sobrevida
10.
Int J Gynaecol Obstet ; 148(1): 96-101, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31560127

RESUMO

OBJECTIVE: To probe the influence of metabolic syndrome (MS) on the long-term survival of patients with non-endometrioid adenocarcinoma. METHODS: Between January 2003 and December 2012, 139 Chinese patients with non-endometrial adenocarcinoma were analyzed in a retrospective study. Patients who had received any treatment before surgery were excluded. Survival times were compared between patients with and without MS. RESULTS: Overall, 41 (29.5%) patients had MS; the highest incidence of MS was observed in those with uterine serous carcinoma (19/45, 42.2%). For uterine serous carcinoma or adenosquamous carcinoma, MS was an independent predictive factor of morbidity (P=0.023 and 0.016, respectively). For the overall population, those with MS had a significantly lower survival rate than those without MS (P=0.008), and the median overall survival (mOS) was 15 months versus 55 months (P<0.001, hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.29-0.69). Similarly, a lower survival rate (P=0.020) and shorter mOS (19 months vs 55 months, P=0.007, HR 0.41, 95% CI 0.20-0.83) were also found in the uterine serous carcinoma population with MS. Multivariate Cox regression analyses showed that disease stage (P=0.023) and MS (P=0.008) were independent prognostic factors for uterine serous carcinoma. CONCLUSION: The present study suggests that MS is a prognostic factor for non-endometrioid adenocarcinoma, especially uterine serous carcinoma.


Assuntos
Carcinoma Adenoescamoso/mortalidade , Cistadenocarcinoma Seroso/mortalidade , Síndrome Metabólica/complicações , Neoplasias Uterinas/mortalidade , Adulto , Idoso , Carcinoma Adenoescamoso/complicações , Carcinoma Adenoescamoso/patologia , Estudos de Casos e Controles , Cistadenocarcinoma Seroso/complicações , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Uterinas/complicações , Neoplasias Uterinas/patologia
11.
Int J Cancer ; 146(7): 1851-1861, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31603993

RESUMO

The goal of our study was to demonstrate the spectrum of genomic alterations present in the residual disease of patients with advanced high-grade serous ovarian cancer (HGSOC) after neoadjuvant chemotherapy (NAC), including matched pretreatment biopsies. During the study period between 2006 and 2017, we collected pre-NAC and post-NAC tumor tissue samples from patients with advanced HGSOC. We performed combined next-generation sequencing and immunohistochemistry to identify actionable targets and pathway activation in post-NAC residual tumors. We also examined whether post-NAC profiling of residual HGSOC identified targetable molecular lesions in the chemotherapy-resistant component of tumors. Among 102 post-NAC samples, 41 (40%) of patients had mutations in homologous recombination repair (HRR) genes (HRR deficiency). Patients with HRR mutations had higher tumor mutation burdens (p < 0.001) and higher alterations in the PI3K-AKT-mTOR pathway (p = 0.004) than patients without these HRR mutations. Nevertheless, we found no significant differences in progression-free survival (p = 0.662) and overall survival (OS; p = 0.828) between the two groups. Most patients (91%) had alterations in at least one of the targetable pathways, and those patients with cell cycle (p = 0.004) and PI3K-AKT-mTOR signaling (p = 0.005) pathway alterations had poorer OS (Bonferroni-corrected threshold = 0.0083, 0.05/6). We showed the genomic landscape of tumor cells remaining in advanced HGSOC after NAC. Once validated, these data can help inform biomarker-driven adjuvant studies in targeting residual tumors to improve the outcomes of patients with advanced HGSOC after NAC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cistadenocarcinoma Seroso/genética , Neoplasias Ovarianas/genética , Ovário/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Ciclo Celular/genética , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/terapia , Procedimentos Cirúrgicos de Citorredução/métodos , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Genômica , Humanos , Pessoa de Meia-Idade , Mutação/efeitos dos fármacos , Terapia Neoadjuvante/métodos , Neoplasia Residual , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/terapia , Ovariectomia/métodos , Ovário/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estudos Retrospectivos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Análise de Sobrevida , Serina-Treonina Quinases TOR/metabolismo
12.
Am J Surg Pathol ; 44(2): 206-213, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31651523

RESUMO

The chemotherapy response score (CRS) is used to score histopathologic response to neoadjuvant chemotherapy (NACT) of patients with extrauterine high-grade serous carcinoma. This study was undertaken to determine if the CRS in the omentum, adnexa or when combined correlates with (1) progression-free survival (PFS) or overall survival (OS), (2) laparoscopic score of abdominal disease, (3) Cancer antigen 125 levels, (4) BRCA status, and (5) platinum-resistant disease. A total of 158 cases were retrospectively collected that received NACT between April 2013 and February 2018 at a single institution. The 3-tier Böhm CRS system was applied to the omentum and adnexa. Survival outcomes between scored subgroups were analyzed using Cox proportional hazards regression. Spearman rank correlation analyses were used to assess CRS and clinical data. A total of 119 cases were treated only with carboplatin/paclitaxel. Omental CRS was: 1 (23 cases, 19.3%), 2 (65 cases, 54.6%), and 3 (31 cases, 26.1%), whereas adnexal CRS was: 1 (50 cases, 42%), 2 (48 cases, 40.3%) and 3 (21 cases, 17.6%). The omental CRS was significantly associated with PFS as a 2-tier score (hazard ratio [HR]=0.612, 95% confidence interval [CI]: 0.378-0.989, P=0.045) but not associated with the PFS using the 3-tier score or with OS using either system. Adnexal CRS was not associated with OS but was significantly associated with PFS using the 3-tier (HR=0.49, 95% CI: 0.263-0.914, P=0.025) and 2-tier scores (HR=0.535, 95% CI: 0.297-0.963, P=0.037). The combined score was not associated with OS but was significantly associated with PFS using the 3-tier (HR=0.348, 95% CI: 0.137-0.88, P=0.026) and 2-tier scores (HR=0.364, 95% CI: 0.148-0.896, P=0.028). No CRS system used associated with laparoscopic assessment of disease. CRS in the omentum had no significant association with platinum resistance; however, the adnexal CRS 1/2 were 3 times as likely to develop platinum resistance compared with CRS 3 (relative risk=3.94, 95% CI: 1.03-15.09, P=0.046). The CRS, when used on the omentum, adnexa, and as a combined score, was significantly associated with PFS but not with OS. Adnexal CRS 1/2 are more likely to develop platinum-resistant disease. Therefore, the use of this pathology parameter may be useful for clinical management.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Regras de Decisão Clínica , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Terapia Neoadjuvante , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias das Tubas Uterinas/mortalidade , Neoplasias das Tubas Uterinas/patologia , Neoplasias das Tubas Uterinas/cirurgia , Feminino , Seguimentos , Humanos , Laparoscopia , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
13.
Neurol India ; 67(6): 1431-1436, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31857529

RESUMO

Aims and Objectives: To review a series of patients with brain metastases from ovarian cancer at a single institution. To describe treatment modalities, their outcomes and to determine prognostic factors. Patients and Methods: Between January 1995 and December 2014, 25 patients with ovarian cancer brain metastases were treated at The Sheba Medical Center. The medical records were retrospectively reviewed to collect demographic, clinical, and imaging data as well as the information on the treatment modalities used and their outcomes. Results: Mean patient age at the time of brain metastasis diagnosis was 62.7 years. The median interval between the diagnosis of primary cancer and brain metastasis was 42.3 months. Neurologic deficits, headache, and seizure were the most common symptoms. The brain was the only site of metastasis in 20% of the patients. Active ovarian cancer at the time of diagnosis of brain metastasis was observed in half of the patients with systemic disease. Multiple brain metastases were observed in 25% of the patients. We treated 11 patients with surgery plus radiation therapy protocols in various orders: surgery followed by complementary whole-brain radiation therapy (WBRT), surgery followed by stereotactic radiosurgery (SRS), and surgery followed by WBRT and then by adjuvant SRS. Five patients underwent surgery alone and nine patients were treated with radiation alone (WBRT, SRS, or both). Univariate analysis for predictors of survival demonstrated that age above 62.7 years at the time of central nervous system involvement was a significant risk factor and leptomeningeal disease was a poor prognostic factor in reference to supra-tentorial lesions. Multivariate analysis for predictors of survival, however, showed that multiple brain lesions (>4) were a poor prognostic factor, and multivariate analysis of the time to progression revealed that combined treatments of surgery and radiation resulted in longer median periods of progression-free survival than each modality alone. Conclusion: We conclude that the only significant predictors of survival or progression-free survival in our cohort were the number of brain metastases and the treatment modality.


Assuntos
Neoplasias Encefálicas/secundário , Irradiação Craniana , Cistadenocarcinoma Seroso/secundário , Procedimentos Neurocirúrgicos , Neoplasias Ovarianas/patologia , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Terapia Combinada , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/terapia , Bases de Dados Factuais , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
14.
EBioMedicine ; 50: 191-202, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31767542

RESUMO

BACKGROUND: Despite toxic side effects and limited durable response, the current standard-of-care treatment for high grade serous ovarian cancer (HGSOC) remains platinum/taxane-based chemotherapy. Given that the overall prognosis has not improved drastically over the past several decades, there is a critical need to understand the underlying mechanisms that lead to tumour development and progression. METHODS: We utilized an integrative proteogenomic analysis of HGSOC tumours applying a poor prognosis gene expression signature (PPS) as a conceptual framework to analyse orthogonal genomic and proteomic data from the TCGA (n = 488) and CPTAC (n = 169) studies. Genes identified through in silico analyses were assessed in vitro studies to demonstrate their impact on proliferation and cell cycle progression. FINDINGS: These analyses identified DNA amplification and overexpression of the transcription factor ADNP (Activity Dependent Neuroprotector Homeobox) in poorly prognostic tumours. Validation studies confirmed the prognostic capacity of ADNP and suggested an oncogenic role for this protein given the association between ADNP expression and pro-proliferative signalling. In vitro studies confirmed ADNP as a novel and essential mediator of cell proliferation through dysregulation of cell cycle checkpoints. INTERPRETATION: We identified ADNP as being amplified and overexpressed in poor prognosis HGSOC in silico analyses and demonstrated that ADNP is a novel and essential oncogene in HGSOC which mediates proliferation through dysregulation of cell cycle checkpoints in vitro. FUNDING: The National Cancer Institute of the National Institutes of Health, the V Foundation for Cancer Research and the New Jersey Commission for Cancer Research.


Assuntos
Ciclo Celular/genética , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Proteogenômica , Biomarcadores Tumorais , Linhagem Celular Tumoral , Proliferação de Células , Biologia Computacional/métodos , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Gradação de Tumores , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Proteogenômica/métodos
15.
Anticancer Res ; 39(11): 5953-5962, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704820

RESUMO

BACKGROUND/AIM: The presence of ascites in ovarian cancer patients is considered a negative prognostic factor. The underlying mechanisms are not clearly understood. MATERIALS AND METHODS: The amount of ascites was evaluated, preferably, using diffusion-weighted MRI at primary diagnosis in a retrospective cohort of 214 women with ovarian cancer, in an ordinal manner (amount of ascites: none, limited, moderate, abundant). In a prospective cohort comprising 45 women with ovarian cancer, IL-10 (interleukin), VEGF (vascular endothelial growth factor), TGF-ß (transforming growth factor) and CCL-2 [chemokine (C-C) motif ligand 2] were measured at diagnosis (and at interval debulking, when available). RESULTS: Gradually increasing amounts of ascites were correlated significantly, even after correction for FIGO stage, with reduced survival (p<0.0001) and stronger immunosuppression (IL10 and VEGF). Neoadjuvant chemotherapy reduced immunosuppression, which was observed as a reduction in CCL-2, IL-10 and VEGF. CONCLUSION: The amount of ascites is an independent predictor of survival and correlates with increased immunosuppression.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ascite/mortalidade , Imunossupressão/mortalidade , Terapia Neoadjuvante/efeitos adversos , Neoplasias Ovarianas/mortalidade , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/imunologia , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/tratamento farmacológico , Adenocarcinoma Mucinoso/imunologia , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/etiologia , Ascite/patologia , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/imunologia , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
16.
DNA Cell Biol ; 38(12): 1519-1528, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31657627

RESUMO

High-grade serous ovarian cancer (HGSOC) is one of the most common and lethal gynecological cancers. Long noncoding RNAs (lncRNAs) play important roles and act as prognostic biomarkers of ovarian cancer. However, few studies have focused on the prognostic prediction of lncRNAs solely in HGSOC. In this study, we identified candidate lncRNAs for a prognostic evaluation by examining reannotated lncRNA expression profiles and clinical data of 343 patients with HGSOC from The Cancer Genome Atlas. We built a 10-lncRNA signature using Cox-LASSO regression to predict the prognosis of patients with HGSOC. Trichotomized by the 10-lncRNA signature, high-risk patients experienced significantly shorter disease-free survival and overall survival (OS). Our novel 10-lncRNA signature showed superior predictive capacity compared to the other 2 published lncRNA signature models and clinicopathological parameters. We developed a nomogram for clinical use by integrating the 10-lncRNA signature and two clinicopathological risk factors to predict 1-, 3-, and 5-year OS. In addition, gene set enrichment analysis suggested that the group of high-risk patients was associated with mitotic spindle pathways. This model was also compatible with patients with or without BRCA1/2 mutations and had the potential to predict the response to platinum-based adjuvant chemotherapy. Our findings provide a novel 10-lncRNA prognostic signature for further clinical application in patients with HGSOC and indicate the underlying mechanisms of HGSOC progression.


Assuntos
Algoritmos , Biomarcadores Tumorais/genética , Cistadenocarcinoma Seroso/mortalidade , Nomogramas , Neoplasias Ovarianas/mortalidade , Modelos de Riscos Proporcionais , RNA Longo não Codificante/genética , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Prognóstico , Fatores de Risco , Taxa de Sobrevida
17.
Theranostics ; 9(22): 6601-6617, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588238

RESUMO

The peritoneal fluid (ascites), replete with abundant tumor-promoting factors and extracellular vesicles (EVs) reflecting the tumor secretome, plays an essential role in ovarian high-grade serous carcinoma (HGSC) metastasis and immune suppression. A comprehensive picture of mediators impacting HGSC progression is, however, not available. Methods: Proteins in ascites from HGSC patients were quantified by the aptamer-based SOMAscan affinity proteomic platform. SOMAscan data were analyzed by bioinformatic methods to reveal clinically relevant links and functional connections, and were validated using the antibody-based proximity extension assay (PEA) Olink platform. Mass spectrometry was used to identify proteins in extracellular microvesicles released by HGSC cells. Results: Consistent with the clinical features of HGSC, 779 proteins in ascites identified by SOMAscan clustered into groups associated either with metastasis and a short relapse-free survival (RFS), or with immune regulation and a favorable RFS. In total, 346 proteins were linked to OC recurrence in either direction. Reanalysis of 214 of these proteins by PEA revealed an excellent median Spearman inter-platform correlation of ρ=0.82 for the 46 positively RFS-associated proteins in both datasets. Intriguingly, many proteins strongly associated with clinical outcome were constituents of extracellular vesicles. These include proteins either linked to a poor RFS, such as HSPA1A, BCAM and DKK1, or associated with a favorable outcome, such as the protein kinase LCK. Finally, based on these data we defined two protein signatures that clearly classify short-term and long-term relapse-free survivors. Conclusion: The ascites secretome points to metastasis-promoting events and an anti-tumor response as the major determinants of the clinical outcome of HGSC. Relevant proteins include both bone fide secreted and vesicle-encapsulated polypeptides, many of which have previously not been linked to HGSC recurrence. Besides a deeper understanding of the HGSC microenvironment our data provide novel potential tools for HGSC patient stratification. Furthermore, the first large-scale inter-platform validation of SOMAscan and PEA will be invaluable for other studies using these affinity proteomics platforms.


Assuntos
Cistadenocarcinoma Seroso/patologia , Neoplasias Ovarianas/patologia , Proteômica/métodos , Microambiente Tumoral , Ascite/metabolismo , Ascite/patologia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Proteínas Sanguíneas/análise , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/mortalidade , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/mortalidade , Recidiva
18.
Eur Rev Med Pharmacol Sci ; 23(19): 8257-8264, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31646556

RESUMO

OBJECTIVE: Ovarian cancer is one of the most common causes of cancer-related deaths in women. Many studies show that dysregulated gene expression plays a key role in tumorigenesis and development. Therefore, a comprehensive understanding of ovarian serous cystadenocarcinoma survival prognosis is needed. PATIENTS AND METHODS: A large number of high-dimensional RNA-sequencing files and clinical datasets collected from the Genomic Data Commons Data Portal were utilized to identify novel potential biomarkers for determining the prognosis of patients with ovarian serous cystadenocarcinoma (OVSC). We adopted a new strategy to identify these biomarkers by integrating co-expression network analysis and the Kaplan-Meier estimation with a non-parametric bootstrapping procedure. RESULTS: Functional enrichment analysis of gene modules of interest revealed several dysregulated genes in OVSC, suggesting a close relationship between hormones and angiogenesis. In combination with this comprehensive approach, 14 genes, including ABCA10, DCX, LRRC30, ALX4, DKK4, SGCZ, ANKS4B, FHL5, SPRR2F, CHRNG, GABRR1, STMN2, CRHBP, and GSTM5, were shown to serve as candidate biomarkers for predicting the prognosis of patients with OVSC. CONCLUSIONS: The current study identified several valuable prognostic biomarkers and several potential therapeutic targets for treating OVSC.


Assuntos
Cistadenocarcinoma Seroso/diagnóstico , Neoplasias Ovarianas/diagnóstico , Biomarcadores/análise , Cistadenocarcinoma Seroso/química , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/mortalidade , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes/genética , Genes Neoplásicos/genética , Marcadores Genéticos/genética , Humanos , Estimativa de Kaplan-Meier , Neoplasias Ovarianas/química , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Ovário/química , Prognóstico , Análise de Sobrevida , Transcriptoma
19.
J Cancer Res Clin Oncol ; 145(11): 2737-2749, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31586262

RESUMO

BACKGROUND: Large tumor suppressor (LATS) proteins are putative tumor suppressors and poorly expressed associated with poor outcome in many cancers. A recent immunohistochemistry study showed that LATS protein expression correlated with poor outcome in serous ovarian cancer. MATERIALS AND METHODS: We analyzed LATS expression in various ovarian cancer transcriptomic data sets and immunohistochemically assessed LATS protein expression in a Swiss ovarian tumor cohort. Results were compared to clinicopathological characteristics and outcome. We also compared LATS protein expression in serous ovarian cancer cell lines to their EMT status (Western blotting) and drug sensitivity (MTT assay). RESULTS: The analysis of 15 different transcriptomic data sets showed that LATS2 was associated with poorer outcome, while LATS1 was irrelevant (HR = 1.19 and HR = 1.00, respectively). The TCGA-RNASeqV2 data set showed that low LATS1 and LATS2 were associated with better survival in serous ovarian carcinoma. Despite heterogeneity among the different data sets, LATS expression is not an indicator of survival in serous ovarian cancer and LATS2 expression may even be tumorigenic. LATS expression was neither associated with survival nor with the stage and grade in the Swiss cohort. It was low in cystadenoma, intermediate in carcinoma, and high in borderline tumors and was higher in serous than mucinous ovarian carcinoma. LATS protein expression extent was comparable in epithelial-, intermediate-, and mesenchymal-type ovarian cancer cells and was not associated with drug sensitivity. CONCLUSION: These results are largely incompatible with a tumor-suppressive function of LATS in ovarian cancer, and LATS protein level is also not an indicator for drug sensitivity and EMT status of ovarian cancer cells.


Assuntos
Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/mortalidade , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Proliferação de Células , Estudos de Coortes , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas
20.
Zhonghua Fu Chan Ke Za Zhi ; 54(9): 595-600, 2019 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-31550775

RESUMO

Objective: To investigate the clinicopathological characteristics and significance of solid, endometrioid and transitional (SET) ovarian high-grade serous carcinoma (HGSC). Methods: A total of 408 cases of ovarian HGSC admitted to Peking University People's Hospital from January 2011 to September 2016 were collected. (1) According to the proportion of tumors with SET form in all tumors, they were divided into three groups: HGSC-classic group (<25%), HGSC-SET Ⅰ (25%-50%) and HGSC-SET Ⅱ (>50%) group. The clinical and pathological characteristics of three groups of ovarian HGSC patients were compared respectively. (2) According to the growth pattern, that was, the proportion of pushing/expanding invasive tumors in the whole pelvic disseminated tumors of pelvic disseminated tumors, the three groups were divided into four subgroups: group A (0-25%), group B (26%-50%), group C (51%-75%) and group D (>75%). Differences in progression-free survival (PFS) among the four subgroups in each group were compared respectively. Results: The median age of 408 cases with ovarian HGSC was 63.3 years (47-78 years), including 152 cases premenopausal and 256 cases postmenopausal. Among 408 cases of ovarian HGSC, 290 cases were in HGSC-classic group, 91 cases in HGSC-SET Ⅰ and 27 cases in HGSC-SET Ⅱ group. (1) There were significant differences in age, proportion of menopausal patients, tumor necrosis (including map necrosis or acne necrosis), response rate to primary chemotherapy, 5-year mortality rate and PFS between HGSC-SET Ⅰ and HGSC-SET Ⅱ (P<0.05). There was no significant difference among the above indexes between HGSC-SET Ⅰ and HGSC-SET Ⅱ (P>0.05). In HGSC-classic group, HGSC-SET Ⅰ and HGSC-SET Ⅱ, the proportion of family members or patients with history of epithelial ovarian cancer or breast cancer increased in turn, and the detection rate of serous tutal intraepithelial carcinoma (STIC) in fallopian tube tissue decreased in turn. There were significant differences between the two groups (P<0.05). (2) In HGSC-classic group, there were 147 cases in group A, 124 cases in group B and 19 cases in group C (0 case in group D), with median PFS of 17.4, 17.7 and 16.5 months respectively (P<0.05); 10, 6, 29 and 46 cases in group A, B, C and D in HGSC-SET Ⅰ, with median PFS of 9.6, 12.7, 30.1 months and 39.0 months respectively, which there were significant difference among group A and C and D (all P<0.05); among group B, C and D group in HGSC-SET Ⅱ, there were respectively 3, 12 and 12 cases (0 case in group A), and the median PFS was 13.5, 34.2 and 47.8 months (P<0.05). PFS was positively correlated with the increase of push/expansive infiltration ratio. Conclusions: The detection rate of STIC in ovarian HGSC patients with SET is higher, the effect of primary chemotherapy is better, and PFS is prolonged. PFS was significantly prolonged in patients with pelvic disseminated tumors of HGSC-SET, the infiltration of which were predominated by pushing or expanding boarder.


Assuntos
Carcinoma Endometrioide/patologia , Cistadenocarcinoma Seroso/patologia , Neoplasias Ovarianas/patologia , Idoso , Carcinoma in Situ , Carcinoma Endometrioide/mortalidade , China/epidemiologia , Cistadenocarcinoma Seroso/mortalidade , Neoplasias das Tubas Uterinas , Tubas Uterinas , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Índice de Gravidade de Doença
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