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1.
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
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
4.
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
5.
Medicine (Baltimore) ; 99(9): e19383, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118786

RESUMO

RATIONALE: Breast metastasis from serous borderline tumor with micro-invasive carcinoma of ovary is a very rare condition. The breast lump as the only clinical presentation is rarely seen in ovarian carcinoma, which may lead to be misdiagnosed, and the mechanism of breast metastasis from ovarian tumors in early stage still needs to be explored. Differentiation from primary breast cancer and extramammary malignancy is crucial because the treatment and prognosis are significantly different. PATIENT CONCERNS: A 33-year-old female presented with a painless, movable, 1.0 × 1.0 cm lump in the upper outer quadrant of the right breast for a month. DIAGNOSES: Breast metastasis of serous borderline tumor with micro-invasive ovarian carcinoma confirmed by pathology and immunohistochemistry. INTERVENTIONS: The patient underwent lumpectomy, bilateral ovarian tumor stripping operation and prophylactic chemotherapy. OUTCOMES: No signs of recurrence have been detected in 1.5 years of follow-up. LESSONS: Distant metastasis may occur in early stage of ovarian carcinoma. It is important to determine the origin of the primary tumor and develop an effective treatment strategy for patients. Imaging findings and pathological diagnostic criteria are important to accurately differentiate between metastasis and primary breast lesions, which may improve the patient's outcomes.


Assuntos
Neoplasias da Mama/diagnóstico , Metástase Neoplásica/diagnóstico , Neoplasias Ovarianas/complicações , Adulto , Neoplasias da Mama/etiologia , Neoplasias da Mama/fisiopatologia , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/etiologia , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Metástase Neoplásica/patologia , Neoplasias Ovarianas/fisiopatologia , Ultrassonografia/métodos
6.
Gynecol Oncol ; 157(2): 329-334, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32094021

RESUMO

OBJECTIVE: To examine the risk of nodal metastases in a contemporary cohort of women based on pathologic risk factors including histology, depth of invasion, tumor grade, and lymphovascular space invasion. METHODS: Women with endometrial cancer who underwent hysterectomy from 2004 to 2016 who were registered in the National Cancer Database were analyzed. Patients were stratified by T stage: T1A (<50% myometrial invasion), T1B (>50% myometrial invasion) and T2 (cervical involvement). Lymph node metastases were assessed in relation to tumor T stage and grade, and further stratified by lymphovascular space invasion. RESULTS: We identified 161,960 patients. The rate of nodal metastases within the endometrioid histology cohort was 2.2% for T1A cancers, 12.8% for T1B cancers and 19.9% for T2 cancers. For stage TIA cancers, the percent of patients with positive nodes increased from 1.1% for grade 1 cancers, to 2.9% for grade 2 cancers to 4.8% for grade 3 cancers. The corresponding rates of nodal metastases for stage T1B cancers were 8.6%, 13.7%, and 16.9%, respectively. For T1A cancers without lymphovascular space invasion, nodal metastases ranged from 0.6% in those with grade 1 cancers to 3.0% for grade 3 cancers. The corresponding risk of nodal disease ranged from 11.8% to 13.9% for T1A cancers with lymphovascular space invasion. CONCLUSIONS: There was a sequential increase in the risk of lymph node metastases based on depth of uterine invasion, tumor grade, and the presence of lymphovascular space invasion. The overall rate of nodal metastasis is lower than reported in the original GOG 33.


Assuntos
Neoplasias do Endométrio/patologia , Linfonodos/patologia , Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/epidemiologia , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/epidemiologia , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia , Estudos de Coortes , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/epidemiologia , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Sistema de Registros , Fatores Socioeconômicos , Estados Unidos/epidemiologia
7.
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
8.
Am J Case Rep ; 21: e920487, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31929500

RESUMO

BACKGROUND Omental calcifications of the peritoneum are typically small and asymptomatic. However, larger psammomatous bodies that cause symptoms such as abdominal pain and bloating are often associated with tumors such as primary serous papillary carcinoma, mesothelioma, or metastatic ovarian cancer. CASE REPORT We describe omental calcifications in a 68-year-old woman who had been asymptomatic for the last 10 years. The case details the histomorphologic features and immunohistochemical signature of a 4.0×3.5×1.0 cm mass consisting of mature adipose tissue that was surgically removed together with an 8.5×6.5×1.8 cm irregular intra-abdominal/mesenteric mass composed of yellow-red fatty tissue. Microscopic sections contained fat with variable clustered classic/psammomatous calcifications, some with a thin epithelioid periphery, in association with a very focal and subtle papillary surface epithelial/mesothelial proliferation. Tumor cell invasion was not observed during examination. Immunohistochemical staining showed that mesothelial cells in the mass were strongly positive for calretinin and focally positive for EMA, CK903, and vimentin. Strong nuclear positivity for PAX8 was also reported. Additional stains were added in response to this pattern, showing strong positivity for CK8, moderate positivity for BAP1, focal positivity for ER, minimal positivity for CD56, and negativity for CK5/6 and D2-40. Three possible explanations are suggested for the phenomenon observed in the pathology slides: reactive mesothelial hyperplasia, well-differentiated papillary mesothelioma, or serous papillary carcinoma of the peritoneum. CONCLUSIONS Findings suggest that these calcifications are a benign, reactive phenomenon, and that the abundance of psammoma bodies may be related to ongoing crops of papillary mesothelial hyperplasia or benign well-differentiated papillary mesothelioma.


Assuntos
Calcinose , Mesotelioma/diagnóstico , Mesotelioma/patologia , Omento/patologia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/patologia , Idoso , Biomarcadores Tumorais , Cistadenocarcinoma Papilar/diagnóstico , Cistadenocarcinoma Seroso/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Hiperplasia/diagnóstico , Imuno-Histoquímica
9.
Gynecol Oncol ; 157(1): 21-28, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31954535

RESUMO

OBJECTIVE: To determine changes in the characteristics of low-grade serous ovarian cancer (LGSOC) and serous borderline ovarian tumor (serous-BOT) in a time-specific manner. METHODS: We conducted a population-based retrospective study examining the Surveillance, Epidemiology, and End Results Program from 1988 to 2000. Trends, demographics, and outcomes of 775 women with well-differentiated serous ovarian cancer, used as a surrogate for LGSOC, were compared to 3937 women with serous-BOT. RESULTS: In the multivariable analysis, women with LGSOC were more likely to be older, have stage II-IV disease, and have undergone hysterectomy at surgery, but less likely to be a Western U.S. resident compared to those with serous-BOT (all, adjusted-P < 0.05). During the study period, the number of LGSOCs decreased by 25.9%, particularly stage I disease (37.6% relative decrease) compared to stage II-IV disease (21.1% relative decrease) (all, P < 0.05). With a median follow-up of 16.9 years, there was a decreasing trend in the 15-year overall survival rates among LGSOC (28.7% relative decrease, P = 0.056) but not in serous-BOT (2.5% relative increase, P = 0.416) as a whole cohort. The magnitude of hazard risk from all-cause death for women with LGSOC compared to those with serous-BOT increased by 68.9% from 1988 to 2000 (P < 0.001). LGSOC remained an independent prognostic factor for decreased overall survival compared to serous-BOT (adjusted-P < 0.05). CONCLUSION: Our study suggests that the decreasing number and survival of LGSOC over time may be due to a diagnosis-shift from LGSOC to serous-BOT. Given the distinct characteristics and outcomes of LGSOC compared to serous-BOT, our study endorses the importance of making the correct diagnosis upfront. Whether this diagnostic-shift supports a hypothesis that serous-BOT is a precursor lesion of LGSOC merits further investigation.


Assuntos
Cistadenocarcinoma Seroso/epidemiologia , Neoplasias Ovarianas/epidemiologia , Fatores Etários , Estudos de Coortes , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Estudos Retrospectivos , Programa de SEER , Estados Unidos/epidemiologia
10.
Virchows Arch ; 477(1): 83-91, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31980961

RESUMO

The response rate to checkpoint inhibitors for women with high-grade serous carcinoma of the ovary, fallopian tube, and peritoneum (HGSC) is modest, and development of predictive biomarkers is needed. The main focus has been on tumor cell PD-L1 expression, but its assessment alone is insufficient for patient selection in most malignancies. We mapped the presence of macrophages (CD68 and CD163) and lymphocytes (CD3) located within the tumor epithelium, the cell type-specific expression of PD-L1 and PD-1, and their impact on 5-year overall survival (OS) in a consecutive cohort of 130 women diagnosed with advanced HGSC between 2011 and 2015. PD-L1 was expressed mainly by macrophages (not by tumor cells) and PD-1 by lymphocytes. Women with higher CD3, PD-L1, and PD-1 expression had improved OS (P = 0.03, P = 0.007, and P = 0.02, respectively). In the external data set (203 women), high expression of CD274 (encoding PD-L1) was associated with improved OS (P = 0.03), in accordance with our results. Furthermore, higher CD163 expression was associated with better outcome in women with no residual tumor after primary surgery (P = 0.02). Thus, women with greater lymphocyte tumor infiltration had better outcome and PD-L1/PD-1 expression, regardless of PD-1/PD-L1 being markers for immune suppressive pathways, conferred a survival benefit in our cohort. Our results highlight that tumor immunity may be harnessed in subsets of HGSC.


Assuntos
Antígeno B7-H1/imunologia , Linfócitos do Interstício Tumoral/patologia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/imunologia , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Linfócitos do Interstício Tumoral/imunologia , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/imunologia , Neoplasias Ovarianas/imunologia , Prognóstico , Receptor de Morte Celular Programada 1/imunologia
11.
Gynecol Oncol ; 156(3): 715-725, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31969252

RESUMO

In January 2019, a group of basic, translational, and clinical investigators and patient advocates assembled in Miami, Florida, to discuss the current state of the science of low-grade serous carcinoma of the ovary or peritoneum-a rare ovarian cancer subtype that may arise de novo or following a diagnosis of serous borderline tumor. The purpose of the conference was to review current knowledge, discuss ongoing research by established researchers, and frame critical questions or issues for future directions. Following presentations and discussions, the primary objective was to initiate future collaborations, uniform database platforms, laboratory studies, and clinical trials to better understand this disease and to advance clinical care outside the boundaries of single academic institutions. This review summarizes the state of the science in five principal categories: epidemiology and patient outcomes, pathology, translational research, patient care and clinical trials, and patients' perspective.


Assuntos
Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/terapia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Animais , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Invasividade Neoplásica , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Curr Oncol Rep ; 22(1): 8, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31989304

RESUMO

PURPOSE OF REVIEW: This review provides an overview of the current clinical standard in low-grade serous ovarian cancer (LGSOC). The available evidence for surgery and standard treatments is elaborated. In addition, we discuss recent findings and novel treatments for LGSOC. RECENT FINDINGS: Two large multicenter trials studying MEK inhibitors in LGSOC have been presented in the last year. Binimetinib demonstrated an activity in LGSOC, especially in KRAS-mutated disease. Trametinib was associated with an improved progression-free survival in relapsed LGSOC. Based on the current results, MEK inhibitors could be an alternative treatment for LGSOC. Surgery is an important step in the treatment of LGSOC. Hormonal therapy and bevacizumab can be beneficial, next to chemotherapy. Targeted treatments, such as the MEK-inhibitor trametinib, seem to be efficient and should be introduced into clinical practice.


Assuntos
Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Quimioterapia Adjuvante , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Feminino , Humanos , Terapia de Alvo Molecular/métodos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Proteínas Proto-Oncogênicas/genética
13.
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
14.
Pathology ; 52(2): 197-205, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31870502

RESUMO

Increasingly, high-grade serous carcinomas (HGSCs) of fallopian tube/ovarian origin are managed initially with neoadjuvant chemotherapy (NACT) and pre-treatment diagnosis is often based upon relatively limited core biopsy and/or cytology specimens. Endometrial HGSC can also present with adnexal and peritoneal metastasis, thus mimicking a primary tubo-ovarian neoplasm, but the role of NACT in these cases is less established. Immunohistochemistry has been considered useful in this distinction but with a wide range of reported findings in the literature. In this study we have examined tumour growth patterns and the expression p16, Ki-67, WT1, PAX2, HER2, ER-α, ER-ß, PR, and BAF250a in 18 tubo-ovarian and 14 endometrial HGSCs, comparing the findings in primary and omental sites. Metastatic tubo-ovarian carcinomas demonstrated significantly more varied architectural patterns than metastatic endometrial HGSCs (median 2.5 versus 1). None of the immunohistochemical markers proved completely reliable but only endometrial HGSC were WT1 negative (7/14 metastatic tumours) or demonstrated over-expression of HER2 (2/14 cases). Micropapillary tumour elements more often showed retained PAX2 and WT1 expression, low Ki-67 labelling, and (in endometrial tumours) PR staining. Diverse architectural patterns suggest tubo-ovarian origin in a metastatic HGSC. Immunohistochemical results should be cautiously interpreted, particularly in small specimens.


Assuntos
Cistadenocarcinoma Seroso/diagnóstico , Neoplasias do Endométrio/diagnóstico , Neoplasias das Tubas Uterinas/diagnóstico , Neoplasias Ovarianas/diagnóstico , Neoplasias Peritoneais/diagnóstico , Biomarcadores Tumorais/análise , Cistadenocarcinoma Seroso/secundário , Diagnóstico Diferencial , Neoplasias do Endométrio/patologia , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Imuno-Histoquímica , Omento/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário
15.
Am J Surg Pathol ; 44(3): 316-328, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31876585

RESUMO

Despite the current classification of high-grade serous carcinoma (HGSCA) and low-grade serous carcinoma (LGSCA) as mutually exclusive diseases based on morphology and molecular pathogenesis, cases with mixed morphologic features of HGSCA and LGSCA have been reported. Herein we assess the clinicopathologic, immunohistochemical (IHC), and molecular genetic characteristics of a group of these cases, which we termed indeterminate grade serous carcinoma (IGSCA) in comparison with groups of HGSCA and LGSCA. Using the World Health Organization (WHO) classification criteria, we selected 27 LGSCA and 19 IGSCA for detailed morphologic study. Thirteen classic HGSCA, 19 classic LGSCA, and 19 IGSCA were selected for p53 and BRAF V600E IHC and molecular genetic testing by next-generation sequencing. IGSCA showed the architectural patterns of invasion of LGSCA, but with higher grade nuclear features focally and a mitotic index intermediate between LGSCA and HGSCA. Few cases in the IGSCA group showed mutant TP53 by IHC or sequencing (4/18, 22.2%), 1 case had mutant BRAF non-V600E by sequencing, and 1 had an NRAS mutation. When present, the mutations were identical in the low-grade and high-grade areas. The IGSCA group had a long-term survival similar to the classic HGSCA group. IGSCA with mixed morphologic features of HGSCA and LGSCA is a rare and potentially clinically aggressive variant of serous carcinoma. Their distinct morphologic, but heterogenous molecular features, including low frequency of TP53 and BRAF mutations suggest that these rare tumors may have a different pathogenesis pathway compared with classic HGSCA and classic LGSCA.


Assuntos
Biomarcadores Tumorais/genética , Cistadenocarcinoma Seroso/diagnóstico , Neoplasias Ovarianas/diagnóstico , Proteínas Proto-Oncogênicas B-raf/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Bases de Dados Factuais , Feminino , GTP Fosfo-Hidrolases/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Prognóstico , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteína Supressora de Tumor p53/metabolismo
16.
F1000Res ; 8: 1630, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807285

RESUMO

Ovarian borderline serous tumors present with peritoneal involvement in 20% of cases, either as non-invasive or invasive implants, also known as extraovarian low-grade serous carcinoma. The coexistence of high-grade serous carcinoma is rare, suggesting a synchronous neoplasia with a distinct and independent tumor biology and behavior. We aim to describe a case of a synchronous ovary-peritoneum neoplasia: serous borderline tumor and primary peritoneal high-grade serous carcinoma. A discussion and literature review concerning the optimal diagnostic and therapeutic approach is provided.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Neoplasias Peritoneais , Cistadenocarcinoma Seroso/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Peritoneais/diagnóstico
17.
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
18.
Cancer Immunol Immunother ; 68(9): 1515-1526, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31515669

RESUMO

OBJECTIVE: To investigate the prognostic and biologic significance of immune-related gene expression in high grade serous ovarian cancer (HGSOC). METHODS: Gene expression dependent survival analyses for a panel of immune related genes were evaluated in HGSOC utilizing The Cancer Genome Atlas (TCGA). Prognostic value of LCK was validated using IHC in an independent set of 72 HGSOC. Prognostic performance of LCK was compared to cytolytic score (CYT) using RNAseq across multiple tumor types. Differentially expressed genes in LCK high samples and gene ontology enrichment were analyzed. RESULTS: High pre-treatment LCK mRNA expression was found to be a strong predictor of survival in a set of 535 ovarian cancers. Patients with high LCK mRNA expression had a longer median progression free survival (PFS) of 29.4 months compared to 16.9 months in those without LCK high expression (p = 0.003), and longer median overall survival (OS) of 95.1 months versus 44.5 months (p = 0.001), which was confirmed in an independent cohort by IHC (p = 0.04). LCK expression was compared to CYT across tumor types available in the TCGA and was a significant predictor of prognosis in HGSOC where CYT was not predictive. Unexpectedly, LCK high samples also were enriched in numerous immunoglobulin-related and other B cell transcripts. CONCLUSIONS: LCK is a better prognostic factor than CYT in ovarian cancer. In HGSOC, LCK high samples were characterized by higher expression of immunoglobulin and B-cell related genes suggesting that a cooperative interaction between tumor infiltrating T and B cells may correlate with better survival in this disease.


Assuntos
Linfócitos B/fisiologia , Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/imunologia , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Neoplasias Ovarianas/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/mortalidade , Citotoxicidade Imunológica , Feminino , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/mortalidade , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida , Transcriptoma
19.
J Cancer Res Clin Oncol ; 145(9): 2251-2259, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31385026

RESUMO

PURPOSE: Fibroblast Growth Factor Receptor 4 (FGFR4) was proposed to hold prognostic significance in high-grade serous ovarian carcinoma (HGSOC). However, information on this deriving from large, representative patient panels is still missing, though such data would be indispensable to validate suitability of FGFR4 as prognostic marker or even pharmacological target. METHODS: 1063 ovarian cancer cases were included in this study. Immunohistochemistry (IHC) was performed using two different anti-FGFR4 specific antibodies (HPA027273, sc-124) on an automated staining system. IHC data of both FGFR4 antibodies were available from 995 cases. FGFR4 immunostaining was correlated to prognostic factors including survival using uni- and multivariate proportional hazard models. RESULTS: FGFR4 was positively associated with advanced FIGO stage, high grade and presence of residual disease. When progression free (PFS) of FGFR4 negative vs. positive patients was compared, patients scored as FGFR4 positive had significantly shortened PFS as compared to those that stained negative. All associations of FGFR4 and shortened PFS were lost during multivariate testing. No significant associations were found in terms of OS. CONCLUSIONS: We were not able to confirm FGFR4 as an independent negative prognosticator as described before. However, FGFR4 was highly prevalent in those cases harboring residual disease after debulking surgery. Since especially patients that could only be debulked sub-optimally may benefit from targeted adjuvant treatment, tyrosine kinase inhibitors targeting FGFRs might turn out to be an interesting future treatment option.


Assuntos
Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/cirurgia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neoplasia Residual , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Análise Serial de Tecidos , Resultado do Tratamento
20.
Tokai J Exp Clin Med ; 44(3): 49-53, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31448396

RESUMO

BACKGROUND: Peritoneal serous papillary carcinoma (PSPC) is a rare disease. It is clinically and histologically similar to progressive ovarian serous adenocarcinoma and involves normal-sized ovaries, making it challenging to diagnose. In this report, we describe a case of peritoneal serous papillary carcinoma that was difficult to identify and how we made a correct diagnosis in order to begin a timely course of treatment. CASE PRESENTATION: A 63-year-old woman with chief complaints of dizziness and abdominal pain was examined, but showed no particular abnormality. Class III cytology of the endometrium was detected through magnetic resonance imaging and a laparotomy was performed on suspicion of endometrial cancer. The patient was finally diagnosed with peritoneal serous papillary carcinoma and was treated with surgical resection and the standard indicated course of chemotherapy. CONCLUSIONS: The diagnosis and treatment of peritoneal serous papillary carcinoma may be delayed or may not be performed unless Class III findings are detected through uterine mucosal cytology before surgery. Surgeons should not hesitate to perform laparotomy when necessary to identify and appropriately treat patients, even if abnormalities are not detected in the preoperative examination.


Assuntos
Cistadenocarcinoma Papilar/diagnóstico , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/patologia , Neoplasias Peritoneais/diagnóstico , Quimioterapia Adjuvante , Cistadenocarcinoma Papilar/patologia , Cistadenocarcinoma Papilar/cirurgia , Cistadenocarcinoma Seroso/cirurgia , Citodiagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Laparotomia , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Neoplasias Ovarianas , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia
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