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1.
Am J Surg Pathol ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31498173

RESUMO

The frequency and prognostic significance of the histologic type in early-stage ovarian cancer (OC) is not as well established as in advanced stages. In addition, histologic typing based only on morphologic features may be difficult, especially in high-grade tumors. In this study, we have analyzed a prospective cohort of 502 early-stage OCs to investigate their frequency, immunohistochemical characteristics, and survival of the 5 main histologic types. Histotype was assigned according to not only the morphologic features but also according to the expression pattern of WT1, p53, Napsin A, and progesterone receptors. In addition, an extended panel including p16, ß-catenin, HER2, Arid1A, HINF1B, CK7, CDX2, and CK20 was used to refine the diagnosis in difficult cases. In this series, the frequency of the 5 major histologic types was as follows: endometrioid carcinoma, 32.7%; clear cell carcinoma, 25.1%; high-grade serous carcinoma (HGSC), 24.7%; mucinous carcinoma, 10.2%; low-grade serous carcinoma, 4.6%; and others, 2.8%. The combination of morphology and immunohistochemistry allowed the reclassification of 23% of OCs. The lowest concordance was found between samples initially diagnosed as endometrioid, but finally classified as high-grade serous tumors (22% error rate). Endometrioid carcinoma was the most favorable histologic type, whereas HGSC and low-grade serous carcinoma had the worst prognosis. Clear cell carcinoma with abnormal p53 immunostaining pattern also had poor prognosis. Although histologic grade was not a prognostic factor among early-stage endometrioid OCs, distinction between grade 3 endometrioid OC and HGSC is recommended, taking into account differences in prognosis and molecular alterations that can guide different treatments.

2.
Am J Surg Pathol ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31464709

RESUMO

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm, of uncertain biological potential, that was recently reported to exhibit recurrent gene fusions involving NCOA2-3. The purpose of this study was to, using a larger sample size, better characterize the histopathologic and molecular diversity of UTROSCT. Twenty-six cases of UTROSCT from 5 institutions were selected for further study. Fluorescence in situ hybridization for NCOA1, NCOA2, NCOA3, ESR1 and GREB1, and targeted RNA sequencing was performed on 17 and 8 UTROSCTs, respectively. Eight cases underwent massively parallel sequencing to detect single nucleotide variants (SNV), copy number variations, and structural variants using a targeted hybrid-capture based assay. NCOA1-3 rearrangement was identified in 81.8% (18/22) of cases. The most common fusion was ESR1-NCOA3, occurring in 40.9% (9/22). GREB1-NCOA1 (n=4), ESR1-NCOA2 (n=3), and GREB1-NCOA2 (n=1) rearrangements were also identified. No recurrent SNVs were identified and no tumor had SNVs in FOXL2, DICER1, STK11, or AKT1, which can be seen in ovarian sex cord-stromal tumors. Copy number variations were infrequent. Clinical follow-up was available for 11 cases with a mean follow-up interval of 94.4 (range, 1 to 319) months. Only one case had a recurrence 66 months after the initial diagnosis and this was the single case with a GREB1-NCOA2 fusion. This study reports the morphologic spectrum of UTROSCT and confirms the recently reported recurrent NCOA2-3 gene fusions, in addition to identifying novel rearrangements involving NCOA1 in these tumors.

3.
Rev. esp. patol ; 52(2): 72-75, abr.-jun. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-182691

RESUMO

Introducción: Exponemos la necesidad de creación de registros de tumores hospitalarios para facilitar la explotación de datos epidemiológicos y el desarrollo de estrategias basadas en la prevención. Material y métodos: Análisis descriptivo retrospectivo de los datos del Registro de Tumores del Hospital La Paz recogiéndose la localización tumoral (CIE-O), método diagnóstico, estadio tumoral y tratamiento. Resultados: Se incluyeron un total de 1.987 casos. La edad media de diagnóstico fue de 66,2 años, el 53,3% de los casos correspondían a varones y el 46,7% a mujeres. Las localizaciones más frecuentes documentadas fueron el aparato digestivo, la piel, la mama y el aparato urinario. El método diagnóstico más frecuentemente usado fue la biopsia (83,1%), seguido de la citología (5,7%). En cuanto al estadio al diagnóstico el 84,5% de los casos se iniciaron como enfermedad localizada, mientras que el 15,4% como enfermedad diseminada. La cirugía fue el tratamiento más frecuente (78,8%) seguido de tratamiento sistémico (16,2%). Conclusión: La implantación de registros de tumores hospitalarios debería ser una prioridad sanitaria con el objetivo de obtener datos epidemiológicos que permitan un mejor conocimiento del cáncer en nuestro medio


Introduction: We present the case for the establishment of hospital tumour registries in order to facilitate the use of epidemiological data and the development of preventive policies. Material and methods: Retrospective descriptive analysis of the data of the tumour registry of the Hospital "La Paz" including tumoral location (ICD-O), diagnostic method, tumour grade and treatment. Results: 1987 cases were included. Median age at diagnosis was 66.2 years; 53.3% of cases were male and 46.7 female. The most frequent tumoral sites recorded were the digestive tract, skin, breast and urinary tract. The most common diagnostic method used was biopsy (83.1%), followed by cytology (5.7%). 84.5% of cases were originally recorded as localized disease, whilst 15.4% were disseminated. Surgery was the most common treatment (78.8%), followed by systemic therapy (16.2%). Conclusion: The establishment of hospital tumour registries should be prioritized, in order to collect epidemiological data which will enhance our understanding of cancer


Assuntos
Humanos , Registros de Doenças/estatística & dados numéricos , Neoplasias/epidemiologia , Registros Hospitalares/estatística & dados numéricos , Pesquisa sobre Serviços de Saúde/tendências , Distribuição por Idade e Sexo
4.
Rev Esp Patol ; 52(2): 72-75, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-30902380

RESUMO

INTRODUCTION: We present the case for the establishment of hospital tumour registries in order to facilitate the use of epidemiological data and the development of preventive policies. MATERIAL AND METHODS: Retrospective descriptive analysis of the data of the tumour registry of the Hospital "La Paz" including tumoral location (ICD-O), diagnostic method, tumour grade and treatment. RESULTS: 1987 cases were included. Median age at diagnosis was 66.2 years; 53.3% of cases were male and 46.7 female. The most frequent tumoral sites recorded were the digestive tract, skin, breast and urinary tract. The most common diagnostic method used was biopsy (83.1%), followed by cytology (5.7%). 84.5% of cases were originally recorded as localized disease, whilst 15.4% were disseminated. Surgery was the most common treatment (78.8%), followed by systemic therapy (16.2%). CONCLUSION: The establishment of hospital tumour registries should be prioritized, in order to collect epidemiological data which will enhance our understanding of cancer.

5.
ACS Sens ; 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30499292

RESUMO

This paper reports the preparation of versatile electrochemical biosensing platforms for the simple, rapid and PCR-independent detection of the most frequent DNA methylation marks (5-methylcytosine, 5-mC, and/or 5-hydroximethylcytosine, 5-hmC) both at global and gene-specific levels. The implemented strategies, relying on the smart coupling of immuno-magnetic beads (MBs), specific DNA probes and amperometric detection at screen-printed carbon electrodes (SPCEs), provided sensitive and selective determination of the target methylated DNAs in less than 90 min with a great reproducibility and demonstrated feasibility for the simultaneous detection of the same or different cytosine epimarks both at global level and in different loci of the same gene or in different genes. The bioplatforms were applied to determine global methylation events in paraffin-embedded colorectal tissues and specific methylation at promoters of tumor suppressor genes in genomic DNA extracted from cancer cells and paraffin-embedded colorectal tissues, and in serum without previous DNA extraction from cancer patients.

6.
Anticancer Res ; 38(9): 5393-5400, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30194194

RESUMO

BACKGROUND/AIM: Predicting response to treatment in high-grade serous ovarian carcinoma (HGSOC) still remains a clinical challenge. The standard-of-care for first-line chemotherapy, based on a combination of carboplatin and paclitaxel, achieves a high response rate. However, the development of drug resistance is one of the major limitations to efficacy. Therefore, identification of biomarkers able to predict response to chemotherapy in patients with HGSOC is a critical step for prognosis and treatment of the disease. Several studies suggest that angiogenesis is an important process in the development of ovarian carcinoma and chemoresistance. The aim of this study was to identify a profile of angiogenesis-related genes as a biomarker for response to first-line chemotherapy in HGSOC. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded samples from 39 patients with HGSOC who underwent surgical cytoreduction and received a first-line chemotherapy with carboplatin and paclitaxel were included in this study. Expression levels of 82 angiogenesis-related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. RESULTS: Univariate analysis identified five genes [angiopoietin 1 (ANGPT1), aryl hydrocarbon receptor nuclear translocator (ARNT), CD34, epidermal growth factor (EGF) and matrix metallopeptidase 3 (MMP3)] as being statistically associated with response to treatment. Multivariable analysis by Lasso-penalized Cox regression generated a model with the combined expression of seven genes [angiotensinogen (AGT), CD34, EGF, erythropoietin receptor (EPOR), interleukin 8 (IL8), MMP3 and MMP7)]. The area under the receiver operating characteristics curve (0.679) and cross-validated Kaplan-Meier survival curves were used to estimate the accuracy of these predictors. CONCLUSION: An angiogenesis-related gene expression profile useful for response prediction in HGSOC was identified, supporting the important role of angiogenesis in HGSOC.


Assuntos
Proteínas Angiogênicas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/métodos , Neoplasias Císticas, Mucinosas e Serosas/tratamento farmacológico , Neoplasias Císticas, Mucinosas e Serosas/genética , Neovascularização Patológica/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Medicina de Precisão/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carboplatina/administração & dosagem , Tomada de Decisão Clínica , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Seleção de Pacientes , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Fatores de Risco , Transcriptoma
7.
Horm Res Paediatr ; 89(6): 397-407, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29895015

RESUMO

BACKGROUND/AIMS: A genomic HABP2 variant was proposed to be responsible for familial nonmedullary thyroid carcinoma (FNMTC). However, its involvement has been questioned in subsequent studies. We aimed to identify genetic HABP2 mutations in a series of FNMTC patients and investigate their involvement in the disease. METHODS: HABP2 was sequenced from 6 index patients. Presence of the variants was investigated in all members of one family. Somatic BRAF and RAS "hotspot" mutations were investigated by the IdyllaTM BRAF Mutation Test and/or Sanger sequencing. RESULTS: Two HABP2 variants (p.E393Q and p.G534E) were identified in the index patient from one family with papillary thyroid carcinoma (PTC) (follicular variant). The prevalence of p.E393Q in Spanish control alleles was 0.5% and that of p.G534E was 5.1%. However, neither change cosegregated with the phenotype in 3 affected members and 5 healthy members of the kindred. Interestingly, all 3 members affected by PTC harbored the p.V600E somatic mutation in BRAF. CONCLUSIONS: The variant G534E is prevalent in the Spanish population (5.1%); however, p.E393Q is rare (< 1%) and none cosegregated with the FNMTC phenotype. The presence of the noninheritable V600E BRAF mutation in this family supports Knudson's "double-hit" hypothesis for cancer development and suggests the involvement of more than 1 gene in the clinical expression of FNMTC.


Assuntos
Carcinoma Papilar/genética , Predisposição Genética para Doença , Mutação de Sentido Incorreto , Síndromes Neoplásicas Hereditárias/genética , Serina Endopeptidases/genética , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Substituição de Aminoácidos , Carcinoma Papilar/epidemiologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Neoplásicas Hereditárias/epidemiologia , Espanha/epidemiologia , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/epidemiologia
8.
Sci Rep ; 8(1): 8485, 2018 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-29855486

RESUMO

Glycosyltransferase enzyme GCNT3, has been proposed as a biomarker for prognosis in colorectal cancer (CRC). Our study goes in depth into the molecular basis of GCNT3 role in tumorigenesis and drug resistance, and it explores its potential role as biomarker in epithelial ovarian cancer (EOC). High levels of GCNT3 are associated with increased sensibility to 5-fluoracil in metastatic cells. Accordingly, GCNT3 re-expression leads to the gain of anti-carcinogenic cellular properties by reducing cell growth, invasion and by changing metabolic capacities. Integrated transcriptomic and proteomic analyses reveal that GCNT3 is linked to cellular cycle, mitosis and proliferation, response to drugs and metabolism pathways. The vascular epithelial growth factor A (VEGFA) arises as an attractive partner of GCNT3 functions in cell invasion and resistance. Finally, GCNT3 expression was analyzed in a cohort of 56 EOC patients followed by a meta-analysis of more than one thousand patients. This study reveals that GCNT3 might constitute a prognostic factor also in EOC, since its overexpression is associated with better clinical outcome and response to initial therapy. GCNT3 emerges as an essential glycosylation-related molecule in CRC and EOC progression, with potential interest as a predictive biomarker of response to chemotherapy.

9.
Rev. esp. patol ; 51(2): 84-96, abr.-jun. 2018. tab
Artigo em Espanhol | IBECS | ID: ibc-171785

RESUMO

Debido a los avances en el conocimiento histológico y molecular del cáncer de ovario, ha sido posible conocer la existencia de 5 subtipos, lo que permite llevar a cabo un enfoque terapéutico más minucioso y un mejor diseño de ensayos clínicos. Cada uno de estos 5subtipos tiene características histológicas específicas y una expresión de biomarcadores propia, así como mutaciones en diferentes genes, algunas de las cuales tienen valor pronóstico y predictivo. CA125 y HE4 son biomarcadores característicos del cáncer de ovario que se utilizan en el diagnóstico y seguimiento de estas enfermedades; sin embargo, en la actualidad, las mutaciones somáticas y germinales en los genes BRCA1 y BRCA2 son los biomarcadores con valor pronóstico y predictivo más importantes en el cáncer de ovario epitelial. En este artículo un grupo de expertos de la Sociedad Española de Oncología Médica y de la Sociedad Española de Anatomía Patológica revisa las características histológicas y moleculares de 5subtipos de cáncer de ovario y describe los biomarcadores y mutaciones más importantes que pueden orientar en el cribado, el diagnóstico y el diseño de estrategias de tratamiento a medida (AU)


Advances in the understanding of the histological and molecular characteristics of ovarian cancer now allow 5subtypes to be identified, leading to a more refined therapeutic approach and improved clinical trials. Each of the subtypes has specific histological features and a particular biomarker expression, as well as mutations in different genes, some of which have prognostic and predictive value. CA125 and HE4 are examples of ovarian cancer biomarkers used in diagnosis and follow-up. Currently, somatic or germinal mutations on BRCA1 and BRCA2 genes are the most important biomarkers in epithelial ovarian cancer, having prognostic and predictive value. In this article, a group of experts from the Spanish Society of Medical Oncology and the Spanish Society of Pathology review the histological and molecular characteristics of the 5subtypes of ovarian cancer and describe the most useful biomarkers and mutations for diagnosis, screening and tailored treatment strategy (AU)


Assuntos
Humanos , Feminino , Neoplasias Ovarianas/patologia , Células Epiteliais/patologia , Biomarcadores Tumorais/análise , Padrões de Prática Médica , Neoplasias Ovarianas/classificação , Programas de Rastreamento/métodos , Detecção Precoce de Câncer/métodos
10.
Angew Chem Int Ed Engl ; 57(27): 8194-8198, 2018 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-29744991

RESUMO

We report a rapid and sensitive electrochemical strategy for the detection of gene-specific 5-methylcytosine DNA methylation. Magnetic beads (MBs) modified with an antibody for 5-methylcytosines (5-mC) are used for the capture of any 5-mC methylated single-stranded (ss)DNA sequence. A flanking region next to the 5-mCs of the captured methylated ssDNA is recognized by hybridization with a synthetic biotinylated DNA sequence. Amperometric transduction at disposable screen-printed carbon electrodes (SPCEs) is employed. The developed biosensor has a dynamic range from 3.9 to 500 pm and a limit of detection of 1.2 pm for the methylated synthetic sequence of the tumor suppressor gene O-6-methylguanine-DNA methyltransferase (MGMT) promoter region. The method is applied in the 45-min analysis of specific methylation in the MGMT promoter region directly in raw spiked human serum samples and in genomic DNA extracted from U-87 glioblastoma cells and paraffin-embedded brain tumor tissues without any amplification and pretreatment step.

11.
Oncotarget ; 9(31): 21893-21903, 2018 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-29774110

RESUMO

Background: Recent reports have identified distinct genomic patterns in ovarian carcinoma, including proliferative and mesenchymal-like groups, with worse outcome. The exact mechanisms driving the onset and progression of these tumors are still poorly understood. Additionally, researchers are concerned about the correct subtype stratification of the available cell line models, and the exploration of alternatives to monolayer culture. Identification of biomarkers to stratify cell lines, characterization of important processes as epithelial-mesenchymal transition (EMT), and the use of three-dimensional (3D) cultures as alternative models could be useful for cell line classification. Methods and Results: In this work, we present a descriptive analysis of 16 commonly used ovarian cancer cell lines. We have studied their morphology in 2- and 3D culture, and their response to cisplatin, observing in the majority of them an increased resistance in 3D. We have also performed an immunohistochemical analysis for proliferation marker Ki-67, and EMT related markers to establish phenotypes. Epithelial cells tend to show higher proliferative rates, and mesenchymal cells show an increase in EMT related markers, especially when cultured in 3D conditions. Conclusions: We have stated the complex heterogeneity of ovarian cancer models, resembling primary tumors, agreeing with the argument that the cell line model for in vitro experiments must be carefully chosen. Our results also support that tridimensional culture could be a very helpful alternative in ovarian cancer research. Regarding EMT, a very important process for the development of this disease, some related biomarkers might be further characterized for their role in this disease development.

12.
Rev Esp Patol ; 51(2): 84-96, 2018 Apr - Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-29602379

RESUMO

Advances in the understanding of the histological and molecular characteristics of ovarian cancer now allow 5subtypes to be identified, leading to a more refined therapeutic approach and improved clinical trials. Each of the subtypes has specific histological features and a particular biomarker expression, as well as mutations in different genes, some of which have prognostic and predictive value. CA125 and HE4 are examples of ovarian cancer biomarkers used in diagnosis and follow-up. Currently, somatic or germinal mutations on BRCA1 and BRCA2 genes are the most important biomarkers in epithelial ovarian cancer, having prognostic and predictive value. In this article, a group of experts from the Spanish Society of Medical Oncology and the Spanish Society of Pathology review the histological and molecular characteristics of the 5subtypes of ovarian cancer and describe the most useful biomarkers and mutations for diagnosis, screening and tailored treatment strategy.

13.
Sci Rep ; 8(1): 6574, 2018 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-29700408

RESUMO

E-cadherin (CDH1) is a putative tumor suppressor gene implicated in breast carcinogenesis. Yet, whether risk factors or survival differ by E-cadherin tumor expression is unclear. We evaluated E-cadherin tumor immunohistochemistry expression using tissue microarrays of 5,933 female invasive breast cancers from 12 studies from the Breast Cancer Consortium. H-scores were calculated and case-case odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression. Survival analyses were performed using Cox regression models. All analyses were stratified by estrogen receptor (ER) status and histologic subtype. E-cadherin low cases (N = 1191, 20%) were more frequently of lobular histology, low grade, >2 cm, and HER2-negative. Loss of E-cadherin expression (score < 100) was associated with menopausal hormone use among ER-positive tumors (ever compared to never users, OR = 1.24, 95% CI = 0.97-1.59), which was stronger when we evaluated complete loss of E-cadherin (i.e. H-score = 0), OR = 1.57, 95% CI = 1.06-2.33. Breast cancer specific mortality was unrelated to E-cadherin expression in multivariable models. E-cadherin low expression is associated with lobular histology, tumor characteristics and menopausal hormone use, with no evidence of an association with breast cancer specific survival. These data support loss of E-cadherin expression as an important marker of tumor subtypes.

14.
Sci Rep ; 8(1): 6418, 2018 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-29686400

RESUMO

This paper describes two different electrochemical affinity biosensing approaches for the simple, fast and bisulfite and PCR-free quantification of 5-methylated cytosines (5-mC) in DNA using the anti-5-mC antibody as biorecognition element. One of the biosensing approaches used the anti-5-mC as capture bioreceptor and a sandwich type immunoassay, while the other one involved the use of a specific DNA probe and the anti-5-mC as a detector bioreceptor of the captured methylated DNA. Both strategies, named for simplicity in the text as immunosensor and DNA sensor, respectively, were implemented on the surface of magnetic microparticles and the transduction was accomplished by amperometry at screen-printed carbon electrodes by means of the hydrogen peroxide/hydroquinone system. The resulting amperometric biosensors demonstrated reproducibility throughout the entire protocol, sensitive determination with no need for using amplification strategies, and competitiveness with the conventional enzyme-linked immunosorbent assay methodology and the few electrochemical biosensors reported so far in terms of simplicity, sensitivity and assay time. The DNA sensor exhibited higher sensitivity and allowed the detection of the gene-specific methylations conversely to the immunosensor, which detected global DNA methylation. In addition, the DNA sensor demonstrated successful applicability for 1 h-analysis of specific methylation in two relevant tumor suppressor genes in spiked biological fluids and in genomic DNA extracted from human glioblastoma cells.

16.
PLoS One ; 12(9): e0183452, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28886093

RESUMO

PURPOSE: To compare the concordance in risk classification between the EndoPredict and the MammaPrint scores obtained for the same cancer samples on 40 estrogen-receptor positive/HER2-negative breast carcinomas. METHODS: Formalin-fixed, paraffin-embedded invasive breast carcinoma tissues that were previously analyzed with MammaPrint as part of routine care of the patients, and were classified as high-risk (20 patients) and low-risk (20 patients), were selected to be analyzed by the EndoPredict assay, a second generation gene expression test that combines expression of 8 genes (EP score) with two clinicopathological variables (tumor size and nodal status, EPclin score). RESULTS: The EP score classified 15 patients as low-risk and 25 patients as high-risk. EPclin re-classified 5 of the 25 EP high-risk patients into low-risk, resulting in a total of 20 high-risk and 20 low-risk tumors. EP score and MammaPrint score were significantly correlated (p = 0.008). Twelve of 20 samples classified as low-risk by MammaPrint were also low-risk by EP score (60%). 17 of 20 MammaPrint high-risk tumors were also high-risk by EP score. The overall concordance between EP score and MammaPrint was 72.5% (κ = 0.45, (95% CI, 0.182 to 0.718)). EPclin score also correlated with MammaPrint results (p = 0.004). Discrepancies between both tests occurred in 10 cases: 5 MammaPrint low-risk patients were classified as EPclin high-risk and 5 high-risk MammaPrint were classified as low-risk by EPclin and overall concordance of 75% (κ = 0.5, (95% CI, 0.232 to 0.768)). CONCLUSIONS: This pilot study demonstrates a limited concordance between MammaPrint and EndoPredict. Differences in results could be explained by the inclusion of different gene sets in each platform, the use of different methodology, and the inclusion of clinicopathological parameters, such as tumor size and nodal status, in the EndoPredict test.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Calmodulina/metabolismo , Proteínas de Transporte/metabolismo , Receptor gp130 de Citocina/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Feminino , Glicoproteínas/metabolismo , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Proteínas Inibidoras de Apoptose/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Proteínas/metabolismo , Receptores de Progesterona/metabolismo , Proteínas Ribossômicas/metabolismo , Survivina , Enzimas de Conjugação de Ubiquitina/metabolismo
18.
Int J Surg Pathol ; 25(4): 339-343, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27881610

RESUMO

Primary leiomyosarcoma arising from the ovarian vein is extremely rare, with only 10 cases reported in the literature. We report on a case of leiomyosarcoma of the left ovarian vein in a 67-year-old woman who presented with abdominal discomfort. Pelvic ultrasound revealed a large, solid, irregular mass in close relation to the left ovary. The patient subsequently underwent a total hysterectomy with bilateral salpingo-oophorectomy. Histologically, the tumor was composed of interlacing fascicles of spindle cells with abundant eosinophilic cytoplasm, hyperchromatic nuclei, and prominent nucleoli. Mitotic activity was high, with 24 mitoses in 10 high-power fields. Areas of necrosis and hemorrhage were present within the tumor. Immunohistochemically, the tumor cells showed diffuse immunoreactivity for vimentin, muscle-specific actin, desmin, and caldesmon. The patient received chemotherapy postoperatively but subsequently developed disseminated metastatic disease (lung, liver, iliac lymph nodes, and peritoneum). Primary leiomyosarcomas arising from the ovarian vein are aggressive neoplasms, and the prognosis correlates with stage.


Assuntos
Leiomiossarcoma/patologia , Neoplasias Vasculares/patologia , Idoso , Feminino , Humanos , Ovário/irrigação sanguínea , Ovário/patologia , Veias/patologia
19.
EBioMedicine ; 13: 132-145, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27720394

RESUMO

In addition to oncogenic drivers, signaling nodes can critically modulate cancer-related cellular networks to strength tumor hallmarks. We identify G-protein-coupled receptor kinase 2 (GRK2) as a relevant player in breast cancer. GRK2 is up-regulated in breast cancer cell lines, in spontaneous tumors in mice, and in a proportion of invasive ductal carcinoma patients. Increased GRK2 functionality promotes the phosphorylation and activation of the Histone Deacetylase 6 (HDAC6) leading to de-acetylation of the Prolyl Isomerase Pin1, a central modulator of tumor progression, thereby enhancing its stability and functional interaction with key mitotic regulators. Interestingly, a correlation between GRK2 expression and Pin1 levels and de-acetylation status is detected in breast cancer patients. Activation of the HDAC6-Pin1 axis underlies the positive effects of GRK2 on promoting growth factor signaling, cellular proliferation and anchorage-independent growth in both luminal and basal breast cancer cells. Enhanced GRK2 levels promote tumor growth in mice, whereas GRK2 down-modulation sensitizes cells to therapeutic drugs and abrogates tumor formation. Our data suggest that GRK2 acts as an important onco-modulator by strengthening the functionality of key players in breast tumorigenesis such as HDAC6 and Pin1.


Assuntos
Neoplasias da Mama/metabolismo , Transformação Celular Neoplásica/metabolismo , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Histona Desacetilases/metabolismo , Peptidilprolil Isomerase de Interação com NIMA/metabolismo , Transdução de Sinais , Acetilação , Animais , Apoptose/genética , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/genética , Modelos Animais de Doenças , Feminino , Quinase 2 de Receptor Acoplado a Proteína G/genética , Expressão Gênica , Desacetilase 6 de Histona , Histona Desacetilases/genética , Humanos , Camundongos Transgênicos , Modelos Biológicos , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/genética , Carga Tumoral
20.
Gynecol Oncol ; 143(1): 54-59, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27498395

RESUMO

OBJECTIVE: To evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the diagnosis of sentinel lymph node (SLN) metastasis compared with histopathological examination in patients with endometrial carcinoma. METHODS: A total of 94 SLNs from 34 patients with endometrial carcinoma were enrolled. The central 1-mm portion of each node was subjected to semi-serial sectioning, sliced at 200-µm intervals and examined by hematoxylin and eosin and cytokeratin 19 (CK19) immunohistochemical staining, and the remaining tissue was analysed by OSNA using CK19 mRNA. The accuracy of the OSNA assay was evaluated based on histopathological diagnosis. RESULTS: Histologically, 89 SLNs were determined to be metastasis negative, and the remaining five SLNs were metastasis positive. Using the breast cancer cutoff value for detecting lymph node metastasis (OSNA criteria for breast cancer, >250copies/µl) the sensitivity of the OSNA assay was 100%; specificity was 87.6%; diagnostic accuracy was 88.3%. Discordant results were recorded for 11 of 94 SLNs. In all 11 cases, a positive result was given by the OSNA assay but not by histopathological examination. In two SLNs from the same patient, histopathological examination revealed the presence of benign epithelial inclusions that were CK19 positive; both SLNs yielded a positive result in the OSNA assay (true-false positive). All remaining nine histologically-negative/OSNA-positive SLNs were classified as micrometastasis (+) by the OSNA assay. CONCLUSION: The OSNA assay shows high sensitivity and specificity, which suggests its utility as a novel tool for the molecular detection of SLN metastasis in patients with endometrial carcinoma.


Assuntos
Neoplasias do Endométrio/patologia , Dosagem de Genes , Queratina-19/genética , Técnicas de Amplificação de Ácido Nucleico , Linfonodo Sentinela/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade
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