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1.
Medicine (Baltimore) ; 99(25): e20278, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569161

RESUMO

RATIONALE: Intracystic papillary breast carcinoma is extremely rare in males with a favorable prognosis. Clinical and mammographic manifestations of IPC are not specific, and no consensus has been reached on its management. PATIENT CONCERNS: Three cases of IPC of the breast in male patients who underwent surgery are presented. In each patient, clinical manifestations, radiological appearance, surgical procedures, pathological diagnosis, and prognosis were investigated. DIAGNOSIS: Ultrasonography showed a complex mass with cystic and nodular solid components in 2 patients and a solid hypoechoic mass in the other 1. Contrast-enhanced ultrasonography(CEUS) was performed for 1 patient demonstrated a solid component of the characteristic enhancement patterns. The final diagnosis of IPC was made after an excisional biopsy. INTERVENTIONS: A mastectomy with sentinel lymph node mapping was carried out in 2 patients, and it was negative for metastatic disease. The third patient received a mastectomy without an investigation of the axillary lymph node status. OUTCOMES: All the patients are disease-free during a median follow-up of 67 months (range, 13-120) months. LESSONS: It is difficult to diagnose IPC of the male breast before surgery, excisional biopsy is necessary. CEUS can be useful to diagnose IPC in male patients in the preoperative evaluation. Sentinel node biopsy may be considered in patients with IPC associated with DCIS or invasive carcinoma.


Assuntos
Neoplasias da Mama Masculina/diagnóstico por imagem , Carcinoma Papilar/diagnóstico por imagem , Idoso , Humanos , Masculino , Mamografia , Ultrassonografia
2.
Zhonghua Zhong Liu Za Zhi ; 42(6): 463-468, 2020 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-32575941

RESUMO

Objective: To explore the differential protein expressions in papillary thyroid carcinoma (PTC) with or without Hashimoto's thyroiditis (HT). Methods: Tissue microarray was prepared and the protein expression levels of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), vascular endothelial growth factor (VEGF), cyclinD1, mesothelial cell (MC) , CD56 and Galectin3 in the PTC tissues with or without HT were detected by immunohistochemical staining. Results: The positive expression rates of BRAF protein in the PTC tissues with or without HT groups were 55.4% (36/65) and 63.6% (42/66), respectively, without significant difference (P=0.336). The positive expression rates of VEGF protein in the PTC tissues with or without HT groups were 25.7% (19/74) and 25.8%(17/66), respectively, without significant difference (P=0.991). The positive expression rates of cyclin D1 protein in the PTC tissues with or without HT groups were 93.4% (71/76) and 97.6% (80/82), without significant difference (P=0.206). The positive expression rates of MC protein in the PTC tissues with or without HT groups were 86.1% (62/72) and 83.5%(71/85), without significant difference (P=0.654). The positive expression rates of Galectin3 protein in the PTC tissues with or without HT groups were 98.7% (76/77) and 97.5% (78/80), without significant difference (P=0.583). The positive expression rates of CD56 in the PTC tissues and adjacent thyroid follicular epithelial cells were 27.4% (32/117) and 65.0% (76/117), respectively, and the difference was statistically significant (P=0.001). The positive expression rates of CD56 in PTC tissues with or without HT were 35.5% (24/68) and 16.5% (13/79), respectively, and the difference was statistically significant (P=0.009). Conclusions: There are no significant differences in the expressions of BRAF, VEGF, CyclinD1, MC and Galectin3 between the PTC tissues with or without HT. However, the significantly differential expression of CD56 between the two group suggests that CD56 may be related to the pathogenesis of PTC with HT. CD56 may be used as a potential molecular marker in PTC diagnosis.


Assuntos
Adenocarcinoma Papilar/genética , Antígeno CD56/metabolismo , Carcinoma Papilar/patologia , Doença de Hashimoto/genética , Proteínas Proto-Oncogênicas B-raf/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adenocarcinoma Papilar/metabolismo , Adenocarcinoma Papilar/patologia , Animais , Biomarcadores/análise , Carcinoma Papilar/metabolismo , Ciclina D1/genética , Galectinas , Doença de Hashimoto/metabolismo , Doença de Hashimoto/patologia , Humanos , Camundongos , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas B-raf/metabolismo , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Análise Serial de Tecidos , Fator A de Crescimento do Endotélio Vascular/genética
4.
Crit Rev Oncol Hematol ; 150: 102970, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32371339

RESUMO

To characterize metanephric tumours in children, we performed a literature review investigating paediatric metanephric adenomas (MA), metanephric stromal tumours (MST) and metanephric adenofibromas (MAF). Including two patients from our own institution (MA, MAF), 110 individual cases (41 MA, 20 MAF, 49 MST) were identified. Additionally, fifteen composite tumours were identified, with areas of MA/MAF and Wilms tumour (WT) or papillary carcinoma. No distinct clinical or radiological features could be defined. In pure metanephric tumours, histologically proven distant metastases were reported once (MA), relapse was reported once (MST) and one tumour-related death occurred (MST). Somatic BRAF-V600E mutations were tested in 15 cases, and identified in 3/6 MA, 3/3 MAF, and 6/6 MST. In our institution the MA harboured a somatic KRAS-G12R mutation. Overall, paediatric metanephric tumours are difficult to discriminate from other renal tumours at presentation, behave relatively benign, and the occurrence of composite tumours warrants analysis of underlying (genetic) pathways.


Assuntos
Adenoma/genética , Adenoma/patologia , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Tumor de Wilms/genética , Tumor de Wilms/patologia , Biomarcadores Tumorais/genética , Criança , Análise Mutacional de DNA , Humanos , Imuno-Histoquímica , Imunofenotipagem , Recidiva Local de Neoplasia
5.
Zhonghua Yi Xue Za Zhi ; 100(14): 1072-1076, 2020 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-32294869

RESUMO

Objective: To analyze the clinical pathological characteristics and incidence of thyroid cancer. Methods: The clinical and pathological data of 21 980 thyroid cancer patients who underwent surgery in the Department of Thyroid Surgery of the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2018, including the gender, age, pathological type, tumor size, tumor number, central and lateral lymph node metastasis, was retrospectively analyzed. Results: There were 16 895 females and 5 085 males (gender ratio: 3.3 to 1), aged 4 to 95 (47.6±11.8) years old. Except for 2012, the average onset age of females was higher than that of males, and both genders showed a trend of early onset over time (females: Z=-2.703, P=0.007; males: Z=-3.004, P=0.003). The proportion of female aged 25 to 39 and male aged 20 to 39 was increasing, but the proportion of both genders aged over 60 was decreasing (all P<0.05). With the increase of tumor length and diameter, the positive rate of central lymph nodes metastasis (Z=-2.205, P=0.027) and lateral lymph node metastasis (Z=-2.205, P=0.027) gradually increased. Conclusions: The onset age of thyroid cancer exhibited a much younger trend, with an increasing proportion of women aged 25-39 and men aged 20-39. Therefore, it should be suggested to strengthen the screening of people in the corresponding age range. The newly diagnosed thyroid cancer was mainly thyroid micropapillary carcinoma, with a high proportion of lymph node metastasis and multiple foci, and thus the optimal treatment methods need to be carefully considered.


Assuntos
Patologia Clínica , Neoplasias da Glândula Tireoide , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Linfonodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tireoidectomia , Adulto Jovem
6.
Medicine (Baltimore) ; 99(16): e19892, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32312017

RESUMO

RATIONALE: The unpredictability of thyroid cancer can be striking, as the disease may rapidly progress to death in some individuals. Herein, we reported a rare case of aggressive papillary thyroid cell carcinoma (PTC) in an elderly patient de-differentiated into squamous cell carcinoma (SCC). PATIENT CONCERNS: We describe a case of a 79-year-old Thai woman presented with hoarseness and neck mass for 2 months and she had been diagnosed with a 3-cm papillary thyroid carcinoma (PTC) in the right side of the thyroid gland. Later on PTC de-differentiated into SCC within 3 years after initial presentation. DIAGNOSIS: De-differentiation from papillary thyroid carcinoma to squamous cell carcinoma. INTERVENTIONS: The patient underwent a total thyroidectomy at the initial hospital and received high dose radioactive iodine (RAI) treatment at our hospital 1 month following the surgery and then was lost to follow-up. Two years later she came back with new development of right solid-cystic neck mass which was found to be recurrent PTC. A radical neck dissection was done and another high dose RAI treatment was given. However, she developed recurrent mass with tenderness at the site above previous solid cystic mass 6 months later. Re-exploration of the neck mass revealed an inflamed midline mass 2 cm with enlarged right lateral cervical lymph nodes. OUTCOMES: A histopathological examination of the midline neck mass showed poorly differentiated SCC with lymphatic invasion. The intermingling of two morphologically distinct tumors, a typical PTC and a poorly differentiated SCC, had been identified in 1 out of 14 excised cervical lymph nodes. The patient underwent external beam radiation without chemotherapy. She is still in stable condition at 18 months post-treatment. LESSONS: This case clearly demonstrated that SCC transformed from a pre-existing PTC. The clinician should consider a possible transformation of papillary thyroid cancer into more aggressive histological types in elderly patients who present with rapidly progressive clinical behavior. However, some patients could have long-term survival if the tumor did not transform into anaplastic thyroid cancer.


Assuntos
Carcinoma Papilar/patologia , Carcinoma de Células Escamosas/patologia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Idoso , Grupo com Ancestrais do Continente Asiático/etnologia , Carcinoma Papilar/radioterapia , Carcinoma Papilar/cirurgia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Diferenciação Celular , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Perda de Seguimento , Excisão de Linfonodo/métodos , Esvaziamento Cervical/métodos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Câncer Papilífero da Tireoide/radioterapia , Câncer Papilífero da Tireoide/cirurgia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Resultado do Tratamento
7.
AJR Am J Roentgenol ; 214(6): 1220-1228, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32286867

RESUMO

OBJECTIVE. This article provides a brief overview of the clinicopathologic and radiologic correlation of 12 renal neoplasms, encompassing the conventional subtypes of renal cell carcinoma and a few of the newly recognized subtypes from the 2016 World Health Organization classification of renal tumors. In addition, we touch upon infrequent neoplasms that may enter the differential diagnosis of a renal mass, with corresponding radiologic and gross images and histologic findings of case-based examples. CONCLUSION. Familiarity with the radiologic and pathologic characteristics of renal cell carcinoma and other renal neoplasms is important to correctly identify and treat these masses.


Assuntos
Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Adenoma/diagnóstico por imagem , Adenoma/patologia , Adenoma Oxífilo/diagnóstico por imagem , Adenoma Oxífilo/patologia , Angiomiolipoma/diagnóstico por imagem , Angiomiolipoma/patologia , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/patologia , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Meios de Contraste , Diagnóstico Diferencial , Humanos , Urotélio/diagnóstico por imagem , Urotélio/patologia
8.
Virchows Arch ; 477(1): 21-31, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32291497

RESUMO

Intestinal-type intraductal papillary mucinous neoplasm (IPMN) of the pancreas is clinicopathologically distinctive. Our research aimed to elucidate the molecular mechanism of the development and progression of the intestinal-type IPMN. In 60 intestinal-type IPMN specimens, histological transitions from gastric-type epithelia to intestinal-type epithelia were observed in 48 cases (80%). CDX2/MUC2/alcian blue triple staining indicated that CDX2 appeared to precede MUC2 expression and subsequent alcian blue-positive mucin production. Expression of p21 and Ki-67 seemed to be accelerated by CDX2 expression (p = 6.02e-13 and p = 3.1e-09, respectively). p21/Ki-67 double staining revealed that p21 was mostly expressed in differentiated cells in the apex of papillae, while Ki-67 was expressed in proliferative cells in the base of papillae. This clear cellular arrangement seemed to break down with the progression of atypical grade and development of invasion (p = 0.00197). Intestinal-type IPMNs harbored frequent GNAS mutations (100%, 25/25) and RNF43 mutations (57%, 8/14) and shared identical GNAS and KRAS mutations with concurrent gastric-type IPMNs or incipient gastric-type neoplasia (100%, 25/25). RNF43 mutations showed emerging or being selected in intestinal-type neoplasms along with ß-catenin aberration. Activation of protein kinase A and extracellular-regulated kinase was observed in CDX2-positive intestinal-type neoplasm. These results suggest that gastric-type epithelia that acquire GNAS mutations together with induction of intrinsic CDX2 expression may evolve with clonal selection and additional molecular aberrations including RNF43 and ß-catenin into intestinal-type IPMNs, which may further progress with complex villous growth due to disoriented cell cycle regulation, acceleration of atypical grade, and advance to show an invasive phenotype.


Assuntos
Fator de Transcrição CDX2/metabolismo , Carcinoma Ductal Pancreático/patologia , Neoplasias Intestinais/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma Mucinoso/patologia , Biomarcadores Tumorais/genética , Carcinoma Papilar/patologia , Diferenciação Celular/fisiologia , Cromograninas/genética , Humanos
9.
Medicine (Baltimore) ; 99(15): e19795, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282744

RESUMO

In the 7th edition of AJCC staging system, cervical lymph node metastases (LNM) in papillary thyroid carcinoma (PTC) is considered as a poorer prognostic indicator only in patients aged 45 years or older, but as a low-risk factor in patients younger than 45 years. The objective of this study is to investigate the influence of cervical LNM on prognostic outcomes of young patients (<45 years' old) with PTC.We carried out a retrospective analysis of 1896 PTC patients younger than 45 years' old at diagnosis, who were firstly treated in our department between January 2005 and December 2014. Clinicopathologic features, recurrences, disease-free survival (DFS) were recorded and analyzed.A total of 1896 consecutive patients were identified, comprising of 426 males and 1470 females after a median follow-up period of 40 months (3-129 months) from initial surgery to disease recurrence or to the end of follow-up. The rate of recurrence was 2.16% (n = 41). The DFS rates for a 1-year, 3-year, or 5-year team were 99.1%, 97.8%, or 97.4%, respectively. Univariate analysis showed that diagnosed age ≤30 years, tumor size >1.0 cm, extrathyroidal extension, multifocal lesions, lesions in bilateral lobes, central neck LNM, and lateral neck LNM were associated with a worse DFS. Multivariate analysis showed that only central neck LNM and lateral neck LNM were significant independent prognostic factors for DFS (P < .001). For patients with papillary thyroid microcarcinoma, cervical LNM were also identified as independent risk factors for DFS (P < .001).LNM have prognostic significance for DFS in PTC patients younger than 45 years. It indicated that PTC patients (<45 years old) with LNM, especially lateral neck LNM, were understaged by the 7th edition of AJCC staging system. Thus, radical resection of primary tumor and metastatic lymph nodes, frequent follow-up, and strict TSH suppression should be taken for young patients with PTC.


Assuntos
Linfonodos/patologia , Metástase Linfática/patologia , Receptores da Tireotropina/antagonistas & inibidores , Câncer Papilífero da Tireoide/patologia , Adulto , Carcinoma Papilar/mortalidade , Carcinoma Papilar/patologia , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Masculino , Margens de Excisão , Pescoço/patologia , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias/métodos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Câncer Papilífero da Tireoide/mortalidade , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/métodos
10.
Ann R Coll Surg Engl ; 102(5): e107-e110, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32233872

RESUMO

The brain is a particularly rare site of metastasis from papillary microcarcinoma, with only few cases described in the literature. We present a case of 59-year-old man who presented with seizures and dysphasia due to left frontal lobe cystic mass, which was excised and turned out on histopathology to be of thyroid origin. Total thyroidectomy was performed and histology showed multifocal papillary microcarcinoma with the largest focus of 3mm with no other adverse features. The patient had ablative radioactive iodine postoperatively, with subsequent exit scan showing no uptake in the brain. Follow-up brain magnetic resonance imaging showed continuous regression of the surgical cavity. Although rare, such cases should be aggressively treated and followed up over the long term, because of reported associated high mortality.


Assuntos
Neoplasias Encefálicas/diagnóstico , Carcinoma Papilar/diagnóstico , Procedimentos Neurocirúrgicos , Convulsões/etiologia , Neoplasias da Glândula Tireoide/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/cirurgia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Carcinoma Papilar/secundário , Carcinoma Papilar/cirurgia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/secundário , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
11.
Life Sci ; 250: 117519, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32147429

RESUMO

OBJECTIVE: Papillary thyroid cancer (PTC) is the most ordinary type of thyroid cancer. Studies pivoting on the mechanisms of microRNAs (miRNAs) are adequately explored but not much on miR-448 in PTC. Thus, this study is proposed to bring forward the uncovered mechanisms of miR-448 in PTC. METHODS: Lysine specific demethylase 5B (KDM5B), miR-448 and transforming growth factor ß-induced factor 1 (TGIF1) expression in PTC tissues and cell lines were detected. The connection between miR-448 expression and clinicopathological characteristics of PTC patients was determined. PTC cell lines TPC-1 and K-1 were transfected with sh-KDM5B, si-TGIF1 or miR-448 mimic to explore their roles in PTC cell progression. Tumor xenografts in nude mice was performed to detect tumor volume and weight. RESULTS: KDM5B and TGIF1 were increased and miR-448 was declined in PTC tissues and cell lines. MiR-448 expression was connected with N stage, lymph node metastasis and advanced tumor node metastasis stage of PTC patients. KDM5B knockdown or TGIF1 reduction or miR-448 elevation undermined PTC cell progression and inhibited tumor growth of nude mice. Down-regulation of miR-448 followed by KDM5B knockdown reversed the effect of decreased KDM5B on the proliferation inhibition and apoptosis promotion of PTC cells. CONCLUSION: Our study elaborates that KDM5B-mediated miR-448 up-regulation restrains PTC cell progression and slows down tumor growth via TGIF1 repression, which provides a novel reference for treatment of PTC.


Assuntos
Carcinoma Papilar/metabolismo , Proteínas de Homeodomínio/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , MicroRNAs/genética , Proteínas Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Idoso , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Metástase Linfática , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Metástase Neoplásica , Transplante de Neoplasias , Proteínas Nucleares/genética , Proteínas Repressoras/genética , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima
12.
J Surg Oncol ; 121(6): 958-963, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32189352

RESUMO

The incidence of papillary thyroid microcarcinoma (microPTC) has dramatically increased in the last decades. Most of these tumors remain small and clinically "silent", only small number progress. Although thyroid surgery used to be the only therapeutic approach, recent guidelines now consider active surveillance for low-risk microPTC. For this reason, more accurate risk stratification of microPTC is needed. The optimal management of low-risk microPTC through accurate risk stratification represents a major clinical issue.


Assuntos
Carcinoma Papilar/diagnóstico , Carcinoma Papilar/terapia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/terapia , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Humanos , Estadiamento de Neoplasias , Fatores de Risco , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
13.
J Surg Oncol ; 121(6): 952-957, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32189361

RESUMO

BACKGROUND: In 2010, a Japanese trial of nonoperative management for papillary thyroid microcarcinomas (PTmC) was published. This study determines if the prevalence of nonoperative management in the United States has changed and if there are predictors of this approach. METHODS: Patients treated for PTmC between 2004 and 2015 in the National Cancer Data Base were identified. Inclusion criteria were: classic or follicular variant papillary cancer histology, tumor size 1 to 10 mm, cN0 disease and no extrathyroidal extension or metastatic disease. Nonoperative management was assessed over time and compared between 2004-2010 and 2010-2015. Logistic regression identified factors associated with nonoperative management. RESULTS: Of 65 381 PTmC patients, 344 (0.5%) were treated nonoperatively. The annual rate of nonoperative management was similar at 0.6% in 2004 to 0.4% in 2010 (P = .755) but increased to 0.9% in 2015 (P < .001). There was no difference in patient age, race, comorbidities, or reason for nonoperative management between the two periods. Academic centers managed more patients nonoperatively. Multivariable logistic regression suggests older age, facility type, location, Hispanic, Asian, and Native American ethnicity were associated with nonoperative management. CONCLUSION: The vast majority of PTmC in the United States is treated with an operation. A small but significant increase in nonoperative management occurred between 2004-2010 and 2010-2015.


Assuntos
Carcinoma Papilar/epidemiologia , Carcinoma Papilar/terapia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/terapia , Carcinoma Papilar/cirurgia , Feminino , Humanos , Modelos Logísticos , Masculino , Oncologia/métodos , Oncologia/estatística & dados numéricos , Pessoa de Meia-Idade , Prevalência , Oncologia Cirúrgica/métodos , Oncologia Cirúrgica/estatística & dados numéricos , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/cirurgia , Estados Unidos/epidemiologia
16.
Mol Genet Genomics ; 295(3): 807-824, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32185457

RESUMO

Patterns of DNA methylation are significantly altered in cancers. Interpreting the functional consequences of DNA methylation requires the integration of multiple forms of data. The recent advancement in the next-generation sequencing can help to decode this relationship and in biomarker discovery. In this study, we investigated the methylation patterns of papillary renal cell carcinoma (PRCC) and its relationship with the gene expression using The Cancer Genome Atlas (TCGA) multi-omics data. We found that the promoter and body of tumor suppressor genes, microRNAs and gene clusters and families, including cadherins, protocadherins, claudins and collagens, are hypermethylated in PRCC. Hypomethylated genes in PRCC are associated with the immune function. The gene expression of several novel candidate genes, including interleukin receptor IL17RE and immune checkpoint genes HHLA2, SIRPA and HAVCR2, shows a significant correlation with DNA methylation. We also developed machine learning models using features extracted from single and multi-omics data to distinguish early and late stages of PRCC. A comparative study of different feature selection algorithms, predictive models, data integration techniques and representations of methylation data was performed. Integration of both gene expression and DNA methylation features improved the performance of models in distinguishing tumor stages. In summary, our study identifies PRCC driver genes and proposes predictive models based on both DNA methylation and gene expression. These results on PRCC will aid in targeted experiments and provide a strategy to improve the classification accuracy of tumor stages.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Metilação de DNA , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/patologia , Carcinoma Papilar/genética , Carcinoma de Células Renais/genética , Estudos de Casos e Controles , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Renais/genética , Regiões Promotoras Genéticas , Transcriptoma
17.
AJR Am J Roentgenol ; 214(5): 1092-1100, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32130045

RESUMO

OBJECTIVE. The purpose of this study is to compare the CT features of colloid carcinoma and tubular adenocarcinoma of the pancreas arising in association with intraductal papillary mucinous neoplasms (IPMNs). MATERIALS AND METHODS. The preoperative CT images of 85 patients with histopathologically proven IPMNs and associated invasive adenocarcinoma located next to each other were retrospectively reviewed. Twenty-nine patients (34.1%; 19 men and 10 women; mean [± SD] age, 68.0 ± 9.5 years) had invasive colloid carcinoma, and 56 patients (65.9%; 31 men and 25 women; mean age, 70.8 ± 10.6 years) had invasive tubular adenocarcinoma. We compared the following CT features between the two groups: IPMN type, main pancreatic duct (MPD) and common bile duct diameters, diameter and characteristics of the largest cystic lesion for branch duct and mixed-type IPMNs, presence of an extracystic or extraductal solid mass next to the cystic lesion or MPD, morphologic features of the upstream MPD in relation to the cystic lesion or solid mass, and presence of a fistula to the adjacent organs. RESULTS. An MPD size of 9.5 mm or greater, a largest cystic lesion diameter of 28 mm or greater, location in the head or neck, septation, calcification, presence of a mural nodule(s) within a cystic lesion or MPD, and presence of a fistula were all more commonly associated with colloid carcinoma. In contrast, presence of an extracystic or extraductal solid mass and an abrupt change in the caliber of the dilated MPD were associated with tubular adenocarcinoma. The best CT feature for differentiating between the two groups was the morphologic features of the upstream MPD in relation to the cystic lesion or solid mass (sensitivity, 81.3%; specificity, 92.3%). CONCLUSION. Preoperative CT is helpful in differentiating two types of invasive carcinoma arising in association with IPMNs. These findings are clinically important because prognosis is better for colloid carcinoma than for tubular adenocarcinoma.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma/diagnóstico por imagem , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Papilar/diagnóstico por imagem , Invasividade Neoplásica/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma/patologia , Adenocarcinoma Mucinoso/patologia , Idoso , Carcinoma Ductal Pancreático/patologia , Carcinoma Papilar/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Invasividade Neoplásica/patologia , Neoplasias Pancreáticas/patologia , Prognóstico
18.
PLoS One ; 15(2): e0228968, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32053670

RESUMO

PURPOSE: To evaluate whether if ultrasonography (US)-based radiomics enables prediction of the presence of BRAFV600E mutations among patients diagnosed as papillary thyroid carcninoma (PTC). METHODS: From December 2015 to May 2017, 527 patients who had been treated surgically for PTC were included (training: 387, validation: 140). All patients had BRAFV600E mutation analysis performed on surgical specimen. Feature extraction was performed using preoperative US images of the 527 patients (mean size of PTC: 16.4mm±7.9, range, 10-85 mm). A Radiomics Score was generated by using the least absolute shrinkage and selection operator (LASSO) regression model. Univariable/multivariable logistic regression analysis was performed to evaluate the factors including Radiomics Score in predicting BRAFV600E mutation. Subgroup analysis including conventional PTC <20-mm (n = 389) was performed (training: 280, validation: 109). RESULTS: Of the 527 patients diagnosed with PTC, 428 (81.2%) were positive and 99 (18.8%) were negative for BRAFV600E mutation. In both total 527 cancers and 389 conventional PTC<20-mm, Radiomics Score was the single factor showing significant association to the presence of BRAFV600E mutation on multivariable analysis (all P<0.05). C-statistics for the validation set in the total cancers and the conventional PTCs<20-mm were lower than that of the training set: 0.629 (95% CI: 0.516-0.742) to 0.718 (95% CI: 0.650-0.786), and 0.567 (95% CI: 0.434-0.699) to 0.729 (95% CI: 0.632-0.826), respectively. CONCLUSION: Radiomics features extracted from US has limited value as a non-invasive biomarker for predicting the presence of BRAFV600E mutation status of PTC regardless of size.


Assuntos
Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/genética , Ultrassonografia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/patologia , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Dados Preliminares , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Radiografia/métodos , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia
20.
Am J Pathol ; 190(3): 702-710, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31953036

RESUMO

Papillary thyroid carcinomas (PTCs) account for 90% of human thyroid cancer cases, which represent 1% of all cancer cases. They are likely to develop from papillary thyroid microcarcinomas (PTMCs), found in up to 36% of healthy individuals, due to rare progression events (0.01%). Although the prognosis of PTCs is excellent, 5% to 10% of tumors display an unfavorable outcome. About 45% of PTCs exhibit activating BRAFV600E mutations. Rats of the inbred BD strains postnatally exposed to the carcinogen N-ethyl-N-nitrosourea developed PTMCs, which closely resembled their human counterparts judging from their histology, size, and marginal tendency to progress. DNA sequencing revealed mutations in exon 15 of the Braf gene identical to the human BRAFV600E mutation in 82% of the cases. Predominantly a 50:50 ratio of wild-type to mutant Braf alleles was seen regardless of tumor size or animal age, indicating that the Braf mutation is an early, if not the initial, event in rat PTMC development. Surprisingly, most PTMCs carrying a confirmed BrafV600E mutation did not display BrafV600E protein expression. As the BrafV600Egene is supposed to be the driver in PTC development, down-regulation of expression should contribute to the low risk for progression of PTMC. This model system will enable further insights into the molecular mechanisms of PTMC initiation and progression to PTC, further translating into targeted tumor prevention strategies/therapies.


Assuntos
Carcinoma Papilar/patologia , Etilnitrosoureia/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Alelos , Substituição de Aminoácidos , Animais , Modelos Animais de Doenças , Éxons/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Mutação , Prognóstico , Ratos , Análise de Sequência de DNA , Câncer Papilífero da Tireoide/induzido quimicamente , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/induzido quimicamente , Neoplasias da Glândula Tireoide/patologia
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