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1.
Anticancer Res ; 39(12): 6915-6921, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810962

RESUMO

BACKGROUND/AIM: The present study aimed to investigate the role of Homebox B2 (HOXB2) in bladder cancer (BC). MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA) dataset was used to analyse HOXB2 expression in BC. The influence of HOXB2 on the cellular functions of BC cells was determined in both HOXB2 knockdown and HOXB2 overexpressed BC cell lines using in vitro assays. RESULTS: HOXB2 mRNA was significantly upregulated in luminal infiltrated and luminal papillary subtypes of BC. Drug Metabolism Cytochrome P450 was significantly enriched in BCs expressing high levels of HOXB2. Knockdown of HOXB2 from EJ138 cells reduced growth, adhesion and invasion. In contrast, overexpression of HOXB2 in RT112 cells induced growth and adhesion of bladder cancer cells. CONCLUSION: Increased HOXB2 expression in papillary BC can promote cell growth and adhesion of BC cells. Drug Metabolism Cytochrome P450 pathway was enriched in BCs overexpressing HOXB2.


Assuntos
Carcinoma Papilar/genética , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genética , Regulação para Cima , Neoplasias da Bexiga Urinária/genética , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sistema Enzimático do Citocromo P-450/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Invasividade Neoplásica
2.
J Surg Oncol ; 120(6): 1023-1030, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31407354

RESUMO

BACKGROUND: Papillary thyroid microcarcinoma exhibits an indolent clinical course and could be a candidate for active surveillance in the appropriate setting. It remains unknown whether papillary microcarcinoma is biologically different from larger papillary carcinoma >1 cm. METHODS: We analyzed clinicopathological information and transcriptome data of papillary thyroid cancer samples from The Cancer Genome Atlas. Propensity-score matching was used to construct a matched cohort consisting of 29 microcarcinomas and 58 carcinomas. Principal component analysis and unsupervised hierarchical cluster analysis were carried out to investigate the similarity of gene expression profiles. RESULTS: After adjustment for differences in baseline clinicopathological and genetic factors, transcriptome could be grouped mainly on the basis of tumor class (BRAF-like vs RAS-like) and tumor size (microcarcinoma vs carcinoma). The gene set enrichment analysis showed that extracellular matrix-associated pathways were enriched in the MSigDB database. CONCLUSION: Papillary thyroid microcarcinomas display a distinct gene expression pattern different from the corresponding carcinomas. We hypothesize that tumor microenvironment may play a role in the microcarcinoma/carcinoma phenotypic divergence.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Papilar/patologia , Pontuação de Propensão , Neoplasias da Glândula Tireoide/patologia , Transcriptoma , Adulto , Carcinoma Papilar/classificação , Carcinoma Papilar/genética , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/classificação , Neoplasias da Glândula Tireoide/genética
4.
Mol Biol Rep ; 46(5): 5287-5294, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31342295

RESUMO

Truncated KIT (tr-KIT) is an alternative variant of c-KIT protein. Previous studies have clearly documented that c-KIT was associated with various oncogenic processes in RCC. However, the biological significance of tr-KIT in RCC development and progression remains unclear. So, it was aimed to investigate the possible association between RCC and tr-KIT which is thought to activate some oncogenic pathways. In this study, Kidney Cancer cDNA Array containing a total of 48 cDNA samples from the normal kidney tissues of 9 healthy subjects and kidney tumor tissues of 10 stage-1, 5 stage-2, 13 stage-3 and 11 stage-4 RCC patients was used for gene expression analysis. Real-Time PCR method was used to measure tr-KIT/c-KIT expression ratios. tr-KIT/c-KIT expression ratio was compared between tumor and normal samples, and statistically correlated with the clinical parameters of RCC patients. tr-KIT/c-KIT expression ratio was approximately 4-times higher in tumor samples than control ones (p = 0.001). Also, tr-KIT/c-KIT expression ratio was approximately two, three and six times higher in Fuhrman nuclear grades 2, 3 and 4 than normal, respectively (p = 0.009). Moreover, clear cell and papillary RCC has a significantly higher level of tr-KIT/c-KIT expression ratio than chromophobe RCC (p = 0.016). In the current study, it was stated for the first time that tr-KIT/c-KIT expression ratio was up-regulated in RCC tissues, and high tr-KIT/c-KIT expression ratio was correlated with more aggressive clinical features and poor patient prognosis. Our results suggest that increased tr-KIT/c-KIT expression ratio might be useful as a prognostic marker for RCC patients.


Assuntos
Processamento Alternativo , Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Proteínas Proto-Oncogênicas c-kit/genética , Regulação para Cima , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Papilar/genética , Carcinoma de Células Renais/genética , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
5.
Med Sci Monit ; 25: 3762-3770, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31107859

RESUMO

BACKGROUND The WD repeat domain 5 (WDR5) is an essential component of methyltransferase complexes. The expression of WDR5 has been reported in several types of malignancy. This study aimed to investigate the expression of the WDR5 gene and protein in a human papillary carcinoma cell line in vitro, including the use WDR5 gene silencing, and the expression of the WDR5 protein in papillary thyroid carcinoma tissue, and clinicopathological characteristics including overall survival (OS). MATERIAL AND METHODS The role of WDR5 in proliferation and migration of the human papillary thyroid carcinoma cell line, KTC-1, was investigated using the cell counting kit-8 (CCK-8) assay and transwell assay after silencing WDR5 expression. Expression levels of WDR5 in 84 patients with papillary thyroid carcinoma were detected using immunohistochemistry. The correlation between WDR5 expression and clinicopathological features was analyzed using the chi-squared test. The prognostic role of WDR5 was evaluated by univariate analysis with the log-rank test, and by multivariate analysis with the Cox regression model. RESULTS WDR5 expression promoted the proliferation and migration of the KTC-1 cells. In tumor tissue from patients with papillary thyroid carcinoma, low expression and high expression levels of WDR5 were found in 72.6% and 27.4%, respectively. Increased expression of WDR5 was significantly associated with lymphatic invasion and reduced survival rates. WDR5 expression was an independent negative prognostic biomarker. CONCLUSIONS Expression of WDR5 promoted cell proliferation and migration in vitro and was associated with reduced prognosis in patients with papillary thyroid carcinoma.


Assuntos
Histona-Lisina N-Metiltransferase/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Progressão da Doença , Feminino , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia
6.
J Clin Lab Anal ; 33(6): e22902, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31021028

RESUMO

BACKGROUND: The BRAFV600E mutation status is a useful diagnostic and prognostic marker for papillary thyroid carcinoma (PTC). Although it is a commonly used method, Sanger sequencing has several limitations in detecting the BRAFV600E mutation. The aim of this study was to evaluate the efficiency of droplet digital PCR (ddPCR) as an alternative method for the detection of the BRAFV600E mutation in PTC patients. METHODS: Samples from a total of 120 patients with PTC and 30 patients with benign nodular thyroid disease who underwent thyroid surgery were collected. The BRAFV600E mutation status of the PTC patients was tested by Sanger sequencing and ddPCR. RESULTS: The BRAFV600E mutation was detected in 67 samples (44.67%) by Sanger sequencing and 92 samples (61.33%) by ddPCR. The detection of the mutation by the two methods was inconsistent in twenty-five samples (16.67%). The sensitivity and specificity of the ddPCR method were 100% and 69.88%, respectively, and the positive predictive and negative predictive values were 72.83% and 100%, respectively. The concordance rate between the two methods in detecting the BRAFV600E mutation was 83.33%. Neither Sanger sequencing nor ddPCR detected BRAFV600E in 30 patients with benign nodular thyroid disease. The 92 samples with the BRAFV600E mutation were detected by ddPCR at a fractional abundance from 0.28% to 45.40% as follows: ≥10% (59 samples, 64.13%), 5%-10% (8 samples, 8.70%), and ≤5% (25 samples, 27.17%). The BRAFV600E mutation was detected in all 59 samples at a fractional abundance ≥10% and in four samples at a fractional abundance from 5% to 10%, and no BRAFV600E mutation was detected at a fractional abundance ≤5% by Sanger sequencing. CONCLUSIONS: ddPCR was a reliable, highly sensitive alternative method for the detection of the BRAFV600E mutation in PTC patients.


Assuntos
Carcinoma Papilar/genética , Reação em Cadeia da Polimerase/métodos , Proteínas Proto-Oncogênicas B-raf/genética , Análise de Sequência de DNA/métodos , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Idoso , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Análise Mutacional de DNA/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Adulto Jovem
7.
Zhonghua Bing Li Xue Za Zhi ; 48(4): 288-292, 2019 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-30955264

RESUMO

Objective: To investigate the prevalence of BRAF V600E mutation in thyroid nodules and to analyze the relationship between BRAF V600E mutation and various clinicopathological features. Methods: BRAF V600E mutant gene test was done in 463 cases of thyroid nodules collected from April 2015 to July 2018 in Beijing Hospital. Pathologic sections of 444 cases of papillary thyroid carcinoma were reviewed and clinical information was collected.Statistical analysis of the relationship between BRAF V600E gene mutation and various clinicopathological features was performed with SPSS 21.0 statistical software. Results: There were 109 males and 354 females in the cohort, with a male to female ratio of 1.0∶3.2. The patient ranged in age from 16 to 82 years, with an average age of 46.1 years. The BRAF V600E mutation rates in papillary thyroid carcinoma, benign thyroid nodules and other thyroid carcinoma were 86.5%(384/444),0/15 and 1/4,respectively.There was significant correlation between BRAF V600E mutation and histological diagnosis of papillary thyroid carcinoma (P<0.05). There was no correlation with age, gender, multifocality, bilaterality, coexisting lymphocytic thyroiditis, nodular goiter, maximum diameter, capsule invasion, extrathyroidal extension and clinical stage (P>0.05). Conclusions: BRAF V600E gene mutation is closely related to the occurrence of papillary thyroid carcinoma. BRAF V600E has significant value in the diagnosis of papillary thyroid carcinoma. While BRAF V600E mutation is related to the histological diagnosis, it shows no correlation with other clinicopathologic features. BRAF V600E mutation is not an independent prognostic factor in papillary thyroid carcinoma patients.


Assuntos
Carcinoma Papilar/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Câncer Papilífero da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/diagnóstico , Adulto Jovem
8.
Asia Pac J Clin Oncol ; 15(5): e154-e161, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30884127

RESUMO

OBJECTIVES: This study aimed at investigating the clinical significance of CEP78 and WDR62 in differentiated thyroid carcinoma (DTC). This study also aimed at finding predictors that help in detecting patients with DTC who have high risk for lateral lymph node metastasis (LNM). METHODS: Quantitative real-time polymerase chain reaction (RT-qPCR) was performed to examine CEP78, and WDR62 mRNA expressions in 40 tissue specimens of DTC, and 40 goiter tissue specimens. Additionally, we reviewed clinical, ultrasound, laboratory, pathological data of patients to analyze the associations between these characteristics and lateral LNM. RESULTS: Our results demonstrated that relative CEP78 mRNA levels were significantly decreased in thyroid cancer tissues than goiter tissues (P = 0.002). ROC curve analysis confirmed the diagnostic value of CEP78 mRNA expression, providing an AUC equals to 0.698 (95% confidence intervals (CI), 0.583-0.813; P = 0.002). The relative WDR62 mRNA expression was not statistically different in DTC tissues and goiter tissues (P = 0.686). Furthermore, the DTC patients had been included to examine risk factors for lateral LNM. In multivariate analysis, the significant factors for predicting lateral LNM were low CEP78 mRNA expression (cut off value ≤0.54; P = 0.03; OR = 19.62; 95% CI, 1.3-296.23), central LNM (P = 0.011; OR = 33.6; 95% CI, 2.24-503.6) and calcifications (P = 0.023; OR = 27.187; 95% CI, 1.57-469.5). CONCLUSIONS: CEP78 can be used as a promising molecular biomarker for differentiation between DTC and goiter tissues, in addition it might serve as a predictor of lateral LNM in DTC along with central LNM and calcifications. Unlike CEP78, WDR62 mRNA expression was not statistically different in DTC and goiter.


Assuntos
Adenocarcinoma Folicular/secundário , Adenocarcinoma/secundário , Biomarcadores Tumorais/metabolismo , Carcinoma Papilar/secundário , Proteínas de Ciclo Celular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/metabolismo , Adulto , Biomarcadores Tumorais/genética , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Proteínas de Ciclo Celular/genética , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Valor Preditivo dos Testes , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo
10.
Biomed Pharmacother ; 114: 108605, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30904818

RESUMO

PURPOSE: microRNAs (miRNAs) play a critical role in drug resistance of multiple cancers including papillary thyroid carcinoma (PTC), indicating the potential of miRNAs as chemoresistance regulators in cancer treatment. The aim of this paper is to explore the relationship between miR-206 and chemoresistance of PTC. METHODS: qRT-PCR was conducted to examine the expression of miR-206 in PTC tissues, parental and TPC-1/euthyrox. The CCK-8 assay, EdU assay and flow cytometry were performed to test cells viability, proliferation and apoptosis, respectively. Luciferase reporter assay was used to confirm the potential target of miR-206. Western blotting analysis was performed to evaluate the expressions of related-proteins. RESULTS: miR-206 was significantly down-regulated in PTC tissues, parental and TPC-1/euthyrox. Moreover, the expression of miR-206 was exceptionally lower in TPC-1/euthyrox cells than that in TPC-1 cells. Furthermore, we found that over-expression of miR-206 could notably decrease the IC50 values both in TPC-1 and TPC-1/euthyrox cells, which indicated that miR-206 played an essential role in the euthyrox resistance in PTC. In addition, up-regulation of miR-206 inhibited the proliferation, induced apoptosis, suppressed the expressions of multidrug resistance-related proteins, including p-gp, MRP, BCRP and LRP, in euthyrox-resistant PTC cells. Besides, over-expression of miR-206 could notably promoted the expression of NIS, an intrinsic membrane protein that mediates the active transport of iodide into the thyroid and other tissues, playing a critical role in the progress. Further, miR-206 was demonstrated to be able to bind to MAP4K3 and negatively regulated the expression of MAP4K3. Besides, MAP4K3 was clearly up-regulated in PTC tissues, parental and TPC-1/euthyrox cells, and down-regulation of miR-206 attenuated the effect of si-MAP4K3 on the euthyrox sensitivity in euthyrox-resistant PTC cells. Moreover, TPC-1/euthyrox cells transfected with miR-206 mimics could significantly inhibit the expressions of p-p38, p-JNK and p-Erk, which indicated that miR-206 might play an essential role in the euthyrox resistance in PTC by negatively regulating the p38 and JNK signaling pathway. CONCLUSION: miR-206 contributed to euthyrox resistance in PTC cells through blockage p38 and JNK signaling pathway by targeting MAP4K3, providing a potential therapeutic application for the treatment of patients with euthyrox-resistant PTC in the further.


Assuntos
Carcinoma Papilar/genética , Resistencia a Medicamentos Antineoplásicos/genética , Sistema de Sinalização das MAP Quinases/genética , MicroRNAs/genética , Proteínas Serina-Treonina Quinases/genética , Câncer Papilífero da Tireoide/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Carcinoma Papilar/tratamento farmacológico , Carcinoma Papilar/patologia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Câncer Papilífero da Tireoide/tratamento farmacológico , Câncer Papilífero da Tireoide/patologia , Glândula Tireoide/efeitos dos fármacos , Tiroxina/farmacologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
11.
Histopathology ; 75(1): 139-145, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30843622

RESUMO

AIMS: Micropapillary variant of mucinous carcinoma of the breast (MPMC) is a rare histological form of oestrogen receptor (ER)-positive invasive carcinoma that is characterised by micropapillary clusters of tumour cells in lakes of extracellular mucin. The aims of this study were to determine the genetic alterations underpinning MPMCs, and to determine whether they overlap with those of mucinous carcinomas and/or invasive micropapillary carcinomas. METHODS AND RESULTS: DNA from five MPMCs was subjected to whole-exome sequencing. Somatic mutations, copy number alterations and mutational signatures were determined with state-of-the-art bioinformatics methods. No mutations in genes significantly mutated in breast cancer, including TP53, PIK3CA, GATA3, and MAP3K1, were detected. We identified copy number alterations that have been reported in invasive micropapillary carcinomas, such as recurrent gains in 1q, 6p, 8q, and 10q, and recurrent losses in 16q, 11q, and 13q, as well as a recurrent 8p12-8p11.2 amplification encompassing FGFR1. Like mucinous carcinomas, three of the five MPMCs analysed lacked PIK3CA mutations, 1q gains, and 16q losses, which are the hallmark genetic alterations of ER-positive breast cancers, whereas two MPMCs harboured 16q losses and/or a complex pattern of copy number alterations similar to those found in breast-invasive micropapillary carcinomas. CONCLUSIONS: MPMCs are heterogeneous at the genetic level; some tumours show a pattern of somatic genetic alterations similar to those of mucinous carcinomas, whereas others resemble invasive micropapillary carcinomas at the genetic level. These findings suggest that MPMCs may not constitute one histological subtype, but rather a convergent phenotype that can stem from mucinous carcinomas or invasive micropapillary carcinomas.


Assuntos
Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Adenocarcinoma Mucinoso/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/metabolismo , Carcinoma Papilar/metabolismo , Variações do Número de Cópias de DNA , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Fenótipo , Receptores Estrogênicos/metabolismo
12.
Endokrynol Pol ; 70(3): 224-231, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30794730

RESUMO

INTRODUCTION: papillary thyroid microcarcinoma is a well-known malignant neoplasm with good prognosis. The known prognostic factors are patient's age, multifocality, and extrathyroidal extension. CD9 and CD82, members of the tetraspanin family, are expressed in numerous cancer cells and play many roles associated with the cellular process. MATERIAL AND METHODS: we investigated the immunohistochemical expression of CD9 and CD82 in papillary thyroid microcarcinoma and analysed the clinicopathological and prognostic significance. For the retrospective analysis, we collected the cases of 553 PTMC patients who had undergone thyroidectomy. RESULTS: The group with lymph node metastasis showed higher immunostaining intensity for CD9 than the group without metastasis (p = 0.002). In multivariate analysis, high CD9 intensity (OR = 1.58 in 3+, p = 0.0025) correlated with lymph node metastasis. CONCLUSION: We suggest CD9 as a predictive prognostic factor for lymph node metastasis in PTMC.


Assuntos
Carcinoma Papilar/diagnóstico , Regulação Neoplásica da Expressão Gênica , Proteína Kangai-1/genética , Tetraspanina 29/genética , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Carcinoma Papilar/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
14.
J Surg Oncol ; 119(6): 777-783, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30636051

RESUMO

BACKGROUND: Breast cancer (BRCA) mutations account for the highest proportion of hereditary causes of pancreatic ductal adenocarcinoma (PDAC). Screening is currently recommended only for patients with one first-degree relative or two family members with PDAC. We hypothesized that screening all BRCA1/2 patients would identify a higher rate of pancreatic abnormalities. METHODS: All BRCA1/2 patients at a single academic center were retrospectively reviewed (2005-2015). Pancreatic abnormalities were defined on cross-sectional imaging as pancreatic neoplasm (cystic/solid) or main-duct dilation. RESULTS: Two hundred and four patients were identified with BRCA mutations. Forty-seven (40%) had abdominal imaging (20 computerized tomography and 27 magnetic resonance imaging). Twenty-one percent had pancreatic abnormalities (PDAC [n = 2] and intraductal papillary mucinous neoplasm [IPMN; n = 8]). The prevalence of pancreatic abnormalities and IPMN was higher in BRCA2 patients than in the general population (21% vs 8% and 17% vs 1%; P = 0.0007 and P < 0.0001, respectively), with no influence of family history. Similarly, BRCA1 patients had an increased prevalence of IPMN (8.3% vs 1%; P < 0.0001). CONCLUSIONS: In this series, 4% and 17% of BRCA2 patients developed PDAC and IPMN, respectively. Eight percent of BRCA1 patients developed IPMN. Under current recommended screening, 60% of BRCA1/2 patients had incompletely pancreatic assessment. With no influence of family history, this study suggests all BRCA1/2 patients should undergo a high-risk screening protocol that will identify a higher rate of precancerous pancreatic neoplasms amenable to curative resection.


Assuntos
Adenocarcinoma/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Dilatação Patológica/genética , Mutação , Ductos Pancreáticos/diagnóstico por imagem , Neoplasias Pancreáticas/genética , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/genética , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/genética , Dilatação Patológica/diagnóstico por imagem , Feminino , Predisposição Genética para Doença , Testes Genéticos , Heterozigoto , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
15.
Clin Nucl Med ; 44(5): 359-364, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30688735

RESUMO

PURPOSE: BRAF V600E mutation papillary thyroid cancer (PTC) is more aggressive with a higher risk of lymph node involvement and a poorer prognosis. Prior studies failed to demonstrate the superiority of prophylactic lymphadenectomy. We investigated the utility of additional radio-guided sentinel node biopsy (SNB). METHODS: We analyzed 15 patients with N0 PTC by ultrasound and BRAF mutation on preoperative biopsy treated with total thyroidectomy (TT) or TT + prophylactic central neck dissection (PCND) alone or with SNB. Conventional surgery was performed before SNB. We recorded primary tumor diameter, multifocality, extrathyroid infiltration, neoplastic emboli, and tall cell variant. At follow-up, we evaluated basal and stimulated thyroglobulin and ultrasound or radioiodine scintigraphy. RESULTS: Of 15 consecutive patients, 5 received conventional surgery alone, and 10 had SNB. For the first group, 4 underwent TT, and 1 had TT + PCND. Among the SNB group, 1 had no sentinel node detected and underwent a simple TT, 2 had TT + PCND+ SNB in the lateral compartment, and 7 had TT + SNB in 1 to 3 neck compartments. Micrometastases were found in 1 of 3 PCND specimens. Sentinel node biopsy revealed metastasis in 3 of 6 central compartment biopsies, in 2 of 6 biopsies in the ipsilateral lateral compartment, and in none of 2 biopsies in the contralateral compartment. Sentinel node biopsy allowed the removal of micrometastases in 4 of 10 patients. At 53 months' (mean) follow-up, no relapse was documented. CONCLUSIONS: Radio-guided SNB correctly and efficiently stages cN0 BRAF-mutated PTC patients. Sentinel node biopsy could limit time-consuming, risk-exposing compartmental prophylactic dissections.


Assuntos
Carcinoma Papilar/patologia , Biópsia de Linfonodo Sentinela/métodos , Câncer Papilífero da Tireoide/patologia , Adulto , Idoso , Carcinoma Papilar/genética , Feminino , Humanos , Biópsia Guiada por Imagem , Masculino , Pessoa de Meia-Idade , Mutação , Projetos Piloto , Proteínas Proto-Oncogênicas B-raf/genética , Biópsia de Linfonodo Sentinela/efeitos adversos , Câncer Papilífero da Tireoide/genética
16.
Ultrasound Q ; 35(3): 228-232, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30601445

RESUMO

OBJECTIVE: The objective of this study was to analyze the association among the thyroid imaging reporting and data system (TI-RADS), quantitative parameters obtained from contrast-enhanced ultrasonography (CEUS), and BRAF V600E mutation status in patients with papillary thyroid microcarcinoma. PATIENTS: From November 2016 to June 2017, 54 patients who had undergone thyroid CEUS and BRAF V600E mutation analysis for papillary thyroid microcarcinoma were enrolled in our study. The patients were divided into 2 groups based on mutation status. Sex, age, pathology results, TI-RADS score, and quantitative CEUS parameters were compared between the 2 groups. RESULTS: There were 43 patients in the BRAF V600E-positive group and 11 patients in the BRAF V600E-negative group. Age and TI-RADS score were not associated with mutation status. The arrival time (17.2 ± 5.1 seconds) and time to peak enhancement (TTP) (26.5 ± 7.4 seconds) of the lesions in the BRAF V600E-positive group were longer than the arrival time (13.2 ± 3.1 seconds) and TTP (21.1 ± 4.4 seconds) of the lesions in the BRAF V600E-negative group. Basic intensity and peak intensity were not associated with mutation status. CONCLUSIONS: There is an association between the arrival time and TTP of CEUS and BRAF V600E mutation status. They may help infer the BRAF V600E mutation status in papillary thyroid carcinoma patients before invasive procedures.


Assuntos
Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/genética , Meios de Contraste , Aumento da Imagem/métodos , Proteínas Proto-Oncogênicas B-raf/genética , Sistemas de Informação em Radiologia/estatística & dados numéricos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/genética , Adulto , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Glândula Tireoide/diagnóstico por imagem , Ultrassonografia/métodos
17.
PLoS One ; 14(1): e0209497, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30645591

RESUMO

The E-cadherin loss has frequently been associated with transcriptional repression mediated by transcription factors, such as the Zinc Finger E-Box Binding Homeobox-2 (ZEB2). Invasive micropapillary carcinomas (IMPCs) of the breast are aggressive neoplasms frequently related to lymph node metastasis and poor overall survival. In the canine mammary gland, IMPCs has just been reported and, based on its behavioral similarity with the human IMPCs, appears to be a good spontaneous model to this human entity. This study aimed to evaluate the relationship between E-cadherin and ZEB2 in a spontaneous canine model of invasive micropapillary carcinoma of the mammary gland. The correlation among gene expression (ZEB2 and CDH1) and clinicopathological findings was also explored. Nineteen cases of IMPC of the canine mammary gland were obtained, protein and mRNA expression were investigated through immunohistochemistry and RNA In Situ Hybridization, respectively. To better understand the relationship between E-cadherin and ZEB2, immunofluorescence was performed in canine IMPCs. Immunohistochemically, most of IMPCs showed 1+ (14/19, 73.7%) for E-cadherin; and positivity for ZEB2 was diagnosed in 47.4% of the IMPCs. Regarding the RNA In Situ Hybridization (ISH), most of IMPCs showed 4+ and 0+ for E-cadherin (CDH1) and ZEB2 respectively. Through immunofluorescence, the first and second more frequent combinatorial group were E-cadherin+ZEB2- and E-cadherin+ZEB2+; neoplastic cells showing concomitantly weak expression for E-cadherin and positivity for ZEB2 were frequently observed. A negative correlation was observed between E-cadherin and progesterone receptor expression in IMPCs. Based on these results, canine mammary IMPCs show E-cadherin lost and, at times reveals nuclear positivity for the transcription factor ZEB2 that seems to exert transcriptional repression of the CDH1.


Assuntos
Carcinoma Papilar/veterinária , Doenças do Cão/genética , Doenças do Cão/metabolismo , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/metabolismo , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo , Animais , Caderinas/genética , Caderinas/metabolismo , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Doenças do Cão/patologia , Cães , Feminino , Regulação Neoplásica da Expressão Gênica , Imuno-Histoquímica , Neoplasias Mamárias Animais/patologia , Invasividade Neoplásica/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
18.
Ann Diagn Pathol ; 40: 189-199, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29454759

RESUMO

Traditionally, papillary renal cell carcinomas (PRCCs) have been divided in two subgroups - type 1 and type 2. Based on recent molecular and genetic developments in the understanding of RCCs, it seems that this traditional classification may not be adequate and that the spectrum of PRCCs is much wider than initially proposed. Small series of distinct types of PRCC which do not fit into the above mentioned categories have been described in the literature. Published studies investigating molecular genetic changes in various types of PRCCs have shown that the molecular genetic features are remarkably heterogeneous across the whole spectrum of PRCCs. Of all PRCC subtypes/variants, PRCC type 1 seems to be a genetically uniform group, while other types showed different degrees of heterogeneity. Among different molecular-genetic features, chromosomal numerical aberration status is one of the most frequently studied features so far. It is becoming more evident that tumor type-specific chromosomal numerical aberration status in PRCCs may not exist. In this review, we present the most current knowledge concerning chromosomal numerical aberration status in PRCCs.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Papilar/genética , Carcinoma de Células Renais/genética , Aberrações Cromossômicas , Neoplasias Renais/genética , Aneuploidia , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/patologia , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Humanos , Rim/patologia , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Masculino
19.
Turk Patoloji Derg ; 35(1): 22-27, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30035295

RESUMO

OBJECTIVE: Nested variant is bland-looking but aggressive subtype of urothelial carcinoma (UC). Cases having significant muscle invasion do not cause problems but small and superficial biopsies may be challenging due to morphological similarities between nested variant urothelial carcinoma and benign urothelial lesions. MATERIAL AND METHOD: We studied Glucose transporter 1 (GLUT-1), which is an integral membrane protein providing glucose pass through plasma membrane down its concentration gradient, to see if it is useful for the differential diagnosis. Twenty five cases of nested variant urothelial carcinoma and a control group consisting of 12 cases of cystitis glandularis, cystitis cystica and 4 cases of inverted papilloma were stained with GLUT-1 immunohistochemically. Membranous staining was scored on a scale of 0 to +3. RESULTS: Eleven of 25 nested variant UC cases showed a score of 2 and 14 of them showed a score of 3 on immunostaining with GLUT-1. Two cases showed a score of 1 and 10 cases did not show any staining in the control group. CONCLUSION: Our results showed that GLUT-1 may be a helpful marker when morphological separation cannot be made between nested variant UC and benign urothelial leisons. We also think that anti-GLUT-1 antibody treatment may be an option in the targeted treatment of nested variant.


Assuntos
Regulação Neoplásica da Expressão Gênica , Transportador de Glucose Tipo 1/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/metabolismo , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/genética , Carcinoma in Situ/metabolismo , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Estudos de Casos e Controles , Diagnóstico Diferencial , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/imunologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Doenças da Bexiga Urinária/diagnóstico , Doenças da Bexiga Urinária/genética , Doenças da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia
20.
Childs Nerv Syst ; 35(1): 169-173, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30069716

RESUMO

INTRODUCTION: Craniopharyngiomas are one of the most frequently diagnosed hypothalamo-pituitary tumors in childhood. The adamantinomatous histological subtype accounts for most pediatric cases, while the papillary variant is almost exclusively diagnosed in adults. Here, we report a case of papillary craniopharyngioma in a very young child, confirmed by molecular tissue analysis. CASE REPORT: A 4-year-old girl was being investigated for symptomatic central hypothyroidism. Brain MR imaging revealed a large solid/cystic suprasellar mass, splaying the optic chiasm and measuring 3 × 1.9 × 2.3 cm. The patient underwent a transsphenoidal near total resection of the lesion, which was encased within a tumor capsule. Post-operatively, the patient developed transient diabetes insipidus but otherwise recovered well. The pathology of the lesion was consistent with a papillary craniopharyngioma with regions of stratified squamous epithelium accompanied by superficial goblet cells and ciliated cells. Subsequent next-generation sequencing analysis of the lesion confirmed the presence of a BRAF V600E mutation (BRAFc.1799T>A p. (Val600Glu). To date, she remains free from progression 1 year following surgery. CONCLUSION: This is the youngest case published to date of papillary craniopharyngioma with a confirmed BRAF V600E mutation. The case encourages discussion about the most appropriate adjuvant therapy for tumor progression in such cases, given the risks of radiotherapy to the developing brain and the increasing availability of oral BRAF inhibitor therapy.


Assuntos
Carcinoma Papilar/genética , Craniofaringioma/genética , Procedimentos Neurocirúrgicos/métodos , Neoplasias Hipofisárias/genética , Proteínas Proto-Oncogênicas B-raf/genética , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/cirurgia , Pré-Escolar , Craniofaringioma/diagnóstico por imagem , Craniofaringioma/cirurgia , Diabetes Insípido/terapia , Feminino , Humanos , Mutação/genética , Testes de Função Hipofisária , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/terapia , Resultado do Tratamento
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