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1.
Cell Commun Signal ; 17(1): 24, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30885209

RESUMO

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) results in changes that promote de-differentiation, migration, and invasion in non-small cell lung cancer (NSCLC). While it is recognized that EMT promotes altered energy utilization, identification of metabolic pathways that link EMT with cancer progression is needed. Work presented here indicates that mesenchymal NSCLC upregulates glutamine-fructose-6-phosphate transaminase 2 (GFPT2). GFPT2 is the rate-limiting enzyme in the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is the obligate activator of O-linked N-acetylglucosamine transferase (OGT). METHODS: Analysis of our transcriptomic data indicates that GFPT2 is one of the most significantly upregulated metabolic genes in mesenchymal NSCLC. Ectopic GFPT2 expression, as well as gene silencing strategies were used to determine the importance of this metabolic enzyme in regulating EMT-driven processes of cell motility and invasion. RESULTS: Our work demonstrates that GFPT2 is transcriptionally upregulated by NF-κB and repressed by the NAD+-dependent deacetylase SIRT6. Depletion of GFPT2 expression in NSCLC highlights its importance in regulating cell migration and invasion during EMT. CONCLUSIONS: Consistent with GFPT2 promoting cancer progression, we find that elevated GFPT2 expression correlates with poor clinical outcome in NSCLC. Modulation of GFPT2 activity offers a potentially important therapeutic target to combat NSCLC disease progression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)/metabolismo , Neoplasias Pulmonares/patologia , NF-kappa B/metabolismo , Sirtuínas/metabolismo , Células A549 , Carcinoma Pulmonar de Células não Pequenas/genética , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Neoplasias Pulmonares/genética , Transdução de Sinais , Ativação Transcricional
2.
Per Med ; 15(3): 199-208, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29843583

RESUMO

Genomic medicine is transforming patient care. However, the speed of development has left a knowledge gap between discovery and effective implementation into clinical practice. Since 2010, the Training Residents in Genomics (TRIG) Working Group has found success in building a rigorous genomics curriculum with implementation tools aimed at pathology residents in postgraduate training years 1-4. Based on the TRIG model, the interprofessional Undergraduate Training in Genomics (UTRIG) Working Group was formed. Under the aegis of the Undergraduate Medical Educators Section of the Association of Pathology Chairs and representation from nine additional professional societies, UTRIG's collaborative goal is building medical student genomic literacy through development of a ready-to-use genomics curriculum. Key elements to the UTRIG curriculum are expert consensus-driven objectives, active learning methods, rigorous assessment and integration.

3.
Ann Diagn Pathol ; 26: 10-15, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28038705

RESUMO

Cyclin D1 protein expression in lymphocytes is classically associated with mantle cell lymphoma. Although increasingly recognized in other lymphoproliferative disorders, cyclin D1 expression and CCND1 gene abnormalities have not been well studied in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Using a double stain for CD20/cyclin D1, we quantified cyclin D1 expression in 10 cases of NLPHL and correlated those findings with SOX11 expression, CCND1 gene abnormalities, and clinical data. For comparison, we examined 5 cases of T cell-/histiocyte-rich large B-cell lymphoma (THRLBCL). All cases of NLPHL stained for cyclin D1 showed at least rare positivity in lymphocyte-predominant (LP) cells. In 4 cases, at least 20% of LP cells were positive for CD20/cyclin D1. Neither SOX11 expression nor CCND1 gene rearrangement was found in any of the cases, but fluorescence in situ hybridization showed a proportion of the large cells with 3 to 4 copies of nonfused IGH and CCND1 signals or 3 intact CCND1 break-apart signals. Further study with CCND1/CEP11 showed polysomy in 6 of 9 cases with cyclin D1 expression and 5 of 16 NLPHL not examined for cyclin D1. Two of 5 cases of THRLBCL showed rare positive staining for CD20/cyclin D1; 1 case showed polysomy with CCND1/CEP11. Results show that cyclin D1 may be expressed in LP cells without SOX11 expression or CCND1 translocation. Polysomy with increased copies of CCND1 may account for cyclin D1 expression in some cases. Cyclin D1 expression is not useful for distinguishing NLPHL from THRLBCL and has no apparent clinical significance in NLPHL.


Assuntos
Biomarcadores Tumorais/metabolismo , Ciclina D1/metabolismo , Doença de Hodgkin/metabolismo , Doença de Hodgkin/patologia , Linfócitos/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Imuno-Histoquímica/métodos , Imunofenotipagem/métodos , Hibridização in Situ Fluorescente/métodos , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Linfoma de Célula do Manto/metabolismo , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Ann Plast Surg ; 76(5): 485-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27070347

RESUMO

INTRODUCTION: Despite the widespread adaptation of acellular dermal matrix (ADM) to breast reconstruction, we are just now exploring how these materials integrate and perform in vivo. The goal of this study was to compare the histological characteristics between expander capsules to an area without the ADM. METHODS: Women undergoing implant-based breast reconstruction at the University of Virginia Health System using a decellularized regenerative dermal matrix were enrolled in this prospective, evaluator-blinded, institutional review board-approved study. Twenty-four non-ADM and 24 ADM breast capsule biopsy specimens were collected from 15 women and analyzed for the histological parameters of inflammation, vascular proliferation, capsule fibrosis, foreign body giant cell inflammatory reaction, and myofibroblasts using a previously described semiquantitative scoring system. The pathologist evaluating the specimens was blinded to the tissue source and biopsy location. RESULTS: There was significantly less inflammation and fewer myofibroblasts in the ADM capsule biopsy samples compared with the no-ADM capsule biopsy samples (inflammation: ADM, 0.83; no-ADM, 1.83; P = 0.001; myofibroblasts: ADM, 0.79; no-ADM, 1.46; P = 0.024). Significantly less vascular proliferation in the ADM samples was seen compared with the no-ADM samples (ADM, 0.75; no-ADM, 1.42; P = 0.036). No statistical difference in the presence of an inflammatory capsule was observed in the no-ADM biopsy samples compared with the ADM capsule biopsy samples (P = 0.060). CONCLUSIONS: When used for staged breast reconstruction, this unique, sterile ADM seems to induce less inflammation. Moreover, the significantly decreased presence of myofibroblasts in this material supports the observed clinical findings of decreased capsular contracture in ADM-assisted breast reconstruction.


Assuntos
Derme Acelular , Implante Mamário/métodos , Mama/patologia , Reação a Corpo Estranho/patologia , Complicações Pós-Operatórias/patologia , Adulto , Idoso , Biópsia , Mama/cirurgia , Feminino , Reação a Corpo Estranho/etiologia , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Método Simples-Cego
5.
Adv Health Sci Educ Theory Pract ; 21(2): 389-99, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26363626

RESUMO

Success in residency matching is largely contingent upon standardized exam scores. Identifying predictors of standardized exam performance could promote primary intervention and lead to design insights for preclinical courses. We hypothesized that clinically relevant courses with an emphasis on higher-order cognitive understanding are most strongly associated with performance on United States Medical Licensing Examination Step exams and National Board of Medical Examiners clinical subject exams. Academic data from students between 2007 and 2012 were collected. Preclinical course scores and standardized exam scores were used for statistical modeling with multiple linear regression. Preclinical courses were categorized as having either a basic science or a clinical knowledge focus. Medical College Admissions Test scores were included as an additional predictive variable. The study sample comprised 795 graduating medical students. Median score on Step 1 was 234 (interquartile range 219-245.5), and 10.2 % (81/795) scored lower than one standard deviation below the national average (205). Pathology course score was the strongest predictor of performance on all clinical subject exams and Step exams, outperforming the Medical College Admissions Test in strength of association. Using Pathology score <75 as a screening metric for Step 1 score <205 results in sensitivity and specificity of 37 and 97 %, respectively, and a likelihood ratio of 11.9. Performance in Pathology, a clinically relevant course with case-based learning, is significantly related to subsequent performance on standardized exams. Multiple linear regression is useful for identifying courses that have potential as risk stratifiers.


Assuntos
Teste de Admissão Acadêmica/estatística & dados numéricos , Educação de Graduação em Medicina/estatística & dados numéricos , Avaliação Educacional/estatística & dados numéricos , Licenciamento em Medicina/estatística & dados numéricos , Estudantes de Medicina/estatística & dados numéricos , Logro , Feminino , Humanos , Masculino , Modelos Estatísticos , Estudos Retrospectivos
6.
Head Neck Pathol ; 9(1): 85-95, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25078757

RESUMO

The recently described mammary analogue secretory carcinoma (MASC) is a low-grade salivary gland malignancy that harbors the recurrent cytogenetic abnormality t(12;15) (p13;q25) ETV6-NTRK3. Confirmation of this is currently considered the gold standard for diagnosis. Some have postulated that morphology together with supporting immunohistochemistry is sufficient to diagnose MASC. In this study we retrospectively review a series of 19 MASCs diagnosed based on histology in conjunction with immunohistochemistry; subsequently we performed in situ hybridization using an ETV6 break-apart probe. Immunohistochemistry for S100 protein and mammaglobin as well as fluorescence in situ hybridization using the Vysis ETV6 Dual Color Break-Apart FISH Probe Kit were performed on all cases. The 19 cases were from 12 females and 7 males with ages ranging from 16 to 76 years (mean = 45 years). Sixteen cases were from the parotid gland, 1 case was from a periparotid lymph node and 2 cases were from the submandibular gland. All 19 cases demonstrated moderate to strong expression of S100 protein. Eighteen cases demonstrated strong, diffuse expression of mammaglobin, while one case had only rare tumor cells that strongly expressed mammaglobin. Eighteen of 19 cases (95 %) demonstrated the ETV6 rearrangement by fluorescence in situ hybridization. Given that morphology together with immunohistochemistry is highly correlated with the ETV6 gene rearrangement, we conclude that molecular confirmation is not required to diagnose MASC.


Assuntos
Imuno-Histoquímica/métodos , Carcinoma Secretor Análogo ao Mamário/diagnóstico , Neoplasias das Glândulas Salivares/diagnóstico , Adolescente , Adulto , Idoso , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Carcinoma Secretor Análogo ao Mamário/genética , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/análise , Proteínas de Fusão Oncogênica/genética , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/genética , Adulto Jovem
7.
Skeletal Radiol ; 44(4): 587-95, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25256753

RESUMO

We report two children with lymphoma of bone centered in the distal femoral epiphysis who presented with knee pain. Radiographs, magnetic resonance imaging (MRI) and computed tomography (CT) were performed on both patients prior to biopsy. Following biopsy, both patients had fluorodeoxyglucose ((18) F-FDG) positron emission tomography/CT (PET/CT) and whole-body technetium-99m (Tc-99m) scintigraphy performed for staging. One patient met the criteria for primary lymphoma of bone. One patient did not meet the criteria for primary lymphoma of bone because of PET uptake in a popliteal, external iliac and possibly lower abdominal node. Both patients responded well to chemotherapy and are disease free more than 7 years after diagnosis. While an epiphyseal presentation of lymphoma of bone is rare, the efficacy of treatment and the compromised outcome associated with diffuse spread of the disease make early recognition by clinicians important. We present these two cases to increase awareness of the disease and to have clinicians consider it in the differential diagnosis of adolescent epiphyseal lesions.


Assuntos
Fêmur/diagnóstico por imagem , Linfoma não Hodgkin/diagnóstico por imagem , Adolescente , Biópsia , Criança , Diagnóstico Diferencial , Epífises/diagnóstico por imagem , Epífises/patologia , Fêmur/patologia , Fluordesoxiglucose F18 , Humanos , Joelho/diagnóstico por imagem , Linfoma/diagnóstico por imagem , Linfoma/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
Genes Dev ; 28(14): 1578-91, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25030697

RESUMO

Lineage or cell of origin of cancers is often unknown and thus is not a consideration in therapeutic approaches. Alveolar rhabdomyosarcoma (aRMS) is an aggressive childhood cancer for which the cell of origin remains debated. We used conditional genetic mouse models of aRMS to activate the pathognomonic Pax3:Foxo1 fusion oncogene and inactivate p53 in several stages of prenatal and postnatal muscle development. We reveal that lineage of origin significantly influences tumor histomorphology and sensitivity to targeted therapeutics. Furthermore, we uncovered differential transcriptional regulation of the Pax3:Foxo1 locus by tumor lineage of origin, which led us to identify the histone deacetylase inhibitor entinostat as a pharmacological agent for the potential conversion of Pax3:Foxo1-positive aRMS to a state akin to fusion-negative RMS through direct transcriptional suppression of Pax3:Foxo1.


Assuntos
Antineoplásicos/farmacologia , Benzamidas/farmacologia , Piridinas/farmacologia , Rabdomiossarcoma Alveolar/patologia , Animais , Linhagem Celular Tumoral , Linhagem da Célula , Modelos Animais de Doenças , Epigênese Genética/efeitos dos fármacos , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Fator de Transcrição PAX3 , Fatores de Transcrição Box Pareados/metabolismo , Proteína Supressora de Tumor p53/metabolismo
11.
Am J Surg Pathol ; 37(4): 571-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23426124

RESUMO

The Ewing sarcoma breakpoint region 1 (EWSR1) is translocated in many sarcomas. Recently, its rearrangement has been described in salivary gland hyalinizing clear cell carcinomas (HCCCs) and in a subset of soft tissue myoepitheliomas. This study examines the presence of the EWSR1 rearrangement in a variety of salivary gland lesions including classic myoepitheliomas and HCCCs. Using a tissue microarray and whole-mount sections, fluorescence in situ hybridization (FISH) was performed on a variety of salivary gland lesions including HCCCs. The EWSR1 rearrangement was detected in 87% of HCCCs (13 of 15); all other salivary gland lesions including classic myoepitheliomas had intact EWSR1. Patients with HCCCs with rearranged EWSR1 included 1 man, 10 women, and 2 of unknown sex. Ages ranged from 35 to 83 years; the tumor size ranged from 0.8 to 5.5 cm, and the involved locations included: palate (2), base of the tongue (2), mandible (2), submandibular gland (2), lip (1), floor of the mouth (1), sublingual gland (1), inner cheek (1), and nasopharynx (1). All HCCCs were composed of sheets and nests of monotonous cells with clear cytoplasm within a hyalinized stroma. All tested cases were immunoreactive with antibodies to p63 and were nonreactive with antibodies to more conventional myoepithelial antigens (e.g., smooth muscle actin and S100 protein). These findings show that the EWSR1 rearrangement is almost a defining feature of HCCCs and also confirm that classic salivary gland myoepitheliomas are distinct from these tumors and do not share a pathogenetic relationship with their soft tissue counterparts.


Assuntos
Adenocarcinoma de Células Claras/genética , Proteínas de Ligação a Calmodulina/genética , Rearranjo Gênico , Mioepitelioma/genética , Proteínas de Ligação a RNA/genética , Neoplasias das Glândulas Salivares/genética , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , DNA de Neoplasias/análise , Feminino , Humanos , Hialina/metabolismo , Hibridização in Situ Fluorescente , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mioepitelioma/metabolismo , Mioepitelioma/secundário , Proteína EWS de Ligação a RNA , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia
12.
Am J Surg Pathol ; 36(9): 1410-4, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22895274

RESUMO

We describe a primary ovarian neoplasm, occurring in a 15-year-old female patient, with morphologic, immunohistochemical, and molecular genetic features identical to those of the very rare tumors of the kidney previously described as "melanotic Xp11 translocation renal cancer." This represents, to the best of our knowledge, the first report of a melanotic Xp11 translocation-associated neoplasm arising outside of the kidney. We discuss the relationship of these rare tumors to neoplasms showing perivascular epithelioid cell differentiation, in particular those showing TFE3 rearrangements.


Assuntos
Biomarcadores Tumorais/genética , Cromossomos Humanos X/genética , Melanoma/genética , Neoplasias Ovarianas/genética , Translocação Genética , Adolescente , Biomarcadores Tumorais/metabolismo , DNA de Neoplasias/análise , Intervalo Livre de Doença , Feminino , Humanos , Hibridização in Situ Fluorescente , Melanoma/metabolismo , Melanoma/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Ovariectomia
13.
Surg Pathol Clin ; 5(4): 961-84, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26838510

RESUMO

The rapid growth of tissue-based molecular pathology has changed the practice of the surgical pathologist signing out soft tissue tumors. This information is presented in a practical and succinct manner focusing on clinically validated findings that have diagnostic or therapeutic relevance. The approach is morphologically based and focuses on differential diagnoses and clinical scenarios. Molecular techniques can be an invaluable ancillary tool.

14.
J Urol ; 186(6): 2359-64, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22019034

RESUMO

PURPOSE: We defined chronic inflammatory cell types in bladder submucosa and the presence of umbrella cells on the surface of bladder epithelium in patients 5 to 21 years old with persistent bacteriuria due to neurogenic bladder and recurrent urinary tract infections associated with vesicoureteral reflux. MATERIALS AND METHODS: Bladder mucosa biopsies from 12 patients and 6 controls were fixed in Carnoy's solution and examined for T cells (CD3, CD4, CD8), B cells (CD79) and plasma cells (CD138). The number of cells in a defined area of submucosa was determined by counting all nuclei in the area. A contiguous section was also stained for uroplakin expression with a monoclonal antibody against uroplakin III to ascertain the integrity of bladder umbrella cells. RESULTS: B cells, plasma cells and lymphoid nodules were found only in patient biopsies. T cell expression was evident in patient and control biopsies. Uroplakin staining of surface epithelium was uniform from control biopsies but spotty or entirely absent from patient biopsies. CONCLUSIONS: Patients with persistent bacteriuria or recurrent urinary tract infections had significant B cell infiltration in the submucosa, including lymphoid nodules. These inflammatory changes are likely due to antigenic stimulation from repeated exposure to bacteria. These changes are associated with frequent absence of uroplakin on surface epithelium.


Assuntos
Linfócitos B/imunologia , Bacteriúria/complicações , Bacteriúria/imunologia , Linfonodos/patologia , Bexiga Urinária/patologia , Infecções Urinárias/complicações , Infecções Urinárias/imunologia , Adolescente , Criança , Pré-Escolar , Humanos , Hiperplasia , Membrana Mucosa/patologia , Recidiva , Bexiga Urinaria Neurogênica/complicações , Bexiga Urinaria Neurogênica/imunologia , Refluxo Vesicoureteral/complicações , Refluxo Vesicoureteral/imunologia , Adulto Jovem
15.
Mol Cancer Ther ; 10(4): 697-707, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21447712

RESUMO

Inhibition of the insulin-like growth factor 1 receptor (Igf1r) is an approach being taken in clinical trials to overcome the dismal outcome for metastatic alveolar rhabdomyosarcoma (ARMS), an aggressive muscle cancer of children and young adults. In our study, we address the potential mechanism(s) of Igf1r inhibitor resistance that might be anticipated for patients. Using a genetically engineered mouse model of ARMS, validated for active Igf1r signaling, we show that the prototypic Igf1r inhibitor NVP-AEW541 can inhibit cell growth and induce apoptosis in vitro in association with decreased Akt and Mapk phosphorylation. However, drug resistance in vivo is more common and is accompanied by Igf1r overexpression, Mapk reactivation, and Her2 overexpression. Her2 is found to form heterodimers with Igf1r in resistant primary tumor cell cultures, and stimulation with Igf2 leads to Her2 phosphorylation. The Her2 inhibitor lapatinib cooperates with NVP-AEW541 to reduce Igf1r phosphorylation and to inhibit cell growth even though lapatinib alone has little effect on growth. These results point to the potential therapeutic importance of simultaneous targeting of Igf1r and Her2 to abrogate resistance.


Assuntos
Pirimidinas/farmacologia , Pirróis/farmacologia , Receptor IGF Tipo 1/antagonistas & inibidores , Rabdomiossarcoma/metabolismo , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Criança , Membrana Corioalantoide/efeitos dos fármacos , Membrana Corioalantoide/patologia , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Embrião de Mamíferos/efeitos dos fármacos , Embrião de Mamíferos/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Lapatinib , Camundongos , Fosforilação/efeitos dos fármacos , Codorniz , Quinazolinas/farmacologia , Interferência de RNA , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rabdomiossarcoma/genética , Rabdomiossarcoma/patologia , Carga Tumoral/efeitos dos fármacos , Células Tumorais Cultivadas , Adulto Jovem
16.
Am J Clin Pathol ; 135(2): 238-44, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21228364

RESUMO

We examined hepatocyte cytokeratin 7 (CK7) expression in chronic allograft rejection (CR), a ductopenic condition in which this has not been systematically evaluated, in 20 patients with the clinicopathologic diagnosis of CR and age-, sex-, and native-disease-matched control subjects. We also studied baseline biopsy specimens from both groups. Three pathologists independently reviewed H&E- and CK7-stained sections, counting interlobular bile ducts (BDs) and portal tracts (PTs), noting the morphologic pattern of injury and scoring hepatocyte CK7 expression (0, none; 1+, rare; 2+, multifocal, predominantly periportal; 3+, extension into the lobule; 4+, diffuse). Mean BD/PT ratios and CK7 scores were calculated. The mean BD/PT ratio (0.58) and CK7 score (1.01) for the "CR, diagnostic" group were significantly different from all other group means (P < .05); no other comparisons were significant (P > .05). A CK7 score of 1 or more was observed in 9 (56%) of 16 CR specimens and in 3 (7%) of 41 remaining specimens. Hepatocyte CK7 expression is frequently noted in CR, and it would appear to reflect ductopenia. CK7 staining may be a useful diagnostic adjunct in evaluation of transplant liver biopsy specimens.


Assuntos
Rejeição de Enxerto/patologia , Hepatócitos/metabolismo , Queratina-7/biossíntese , Transplante de Fígado/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/fisiopatologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade
17.
Skeletal Radiol ; 40(2): 233-7, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20803341

RESUMO

We present the first report of a patient with angiomatoid fibrous histiocytoma of bone in the radiology literature. This tumor initially eluded diagnosis due to its similarities with chronic hematoma and aneurysmal bone cyst. Only two cases of angiomatoid fibrous histiocytoma have been reported in the radiology literature and both of these lesions were in the soft tissues. The fairly distinctive findings in our patient of multiple large cystic chambers with fluid-fluid levels are similar to the findings in the two soft tissue case reports, suggesting that imaging may be used to suggest this specific diagnosis regardless of location, especially in the clinical setting of unexplained hematoma or anemia. Mention of this diagnosis in the radiology report may aid in the final diagnosis at pathology, because special techniques, including fluorescent in situ hybridization, must be applied in order to fully evaluate for the diagnosis.


Assuntos
Neoplasias Ósseas/diagnóstico , Histiocitoma Fibroso Benigno/diagnóstico , Ísquio/diagnóstico por imagem , Ísquio/patologia , Imagem por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Pré-Escolar , Humanos , Masculino
18.
Hum Pathol ; 41(8): 1138-44, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20381117

RESUMO

More than half a million endoscopic retrograde cholangiopancreatography (ERCP) procedures are performed annually in the United States. The risk of severe complications after ERCP is less than 1%; however, autopsy pathologists see a select group of patients having fatality. Thirty-five autopsies were performed after ERCP over a 13-year period. Fourteen of these 35 patients died of ERCP complications. The remaining patients formed the control group. Fatal complications of ERCP included acute pancreatitis (7), sepsis (5), gastrointestinal/biliary perforation (3), bleeding (2), myocardial infarction (2), and cardiac arrhythmia (1). Cancer (14) and chronic pancreatitis (4) were the most reported causes of death in the control group. Median times to death after ERCP in ERCP-related deaths versus controls were 9.5 and 40 days, respectively. The most common indications for the procedure in ERCP-related deaths were suspected choledocholithiasis and jaundice/biliary obstruction; in controls, jaundice/biliary obstruction and chronic pancreatitis were more common. Patients having fatal ERCP complications had more cannulations reported as "difficult" (69% versus 20%; P = .003). The Klöppel chronic pancreatitis score was lower (mean, 2.6 versus 6.6; P = .03), and the percentage of nonfibrotic pancreatic parenchyma was higher (mean, 85% versus 56%; P = .02) in ERCP-related death group versus controls. Although patients rarely die after ERCP, our findings suggest that healthy acinar tissue is a risk factor for ERCP-related death, especially in the setting of difficult cannulation.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Complicações do Diabetes/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Virginia/epidemiologia
19.
Cancer Res ; 69(7): 2902-11, 2009 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-19339268

RESUMO

The highly aggressive muscle cancer alveolar rhabdomyosarcoma (ARMS) is one of the most common soft tissue sarcoma of childhood, yet the outcome for the unresectable and metastatic disease is dismal and unchanged for nearly three decades. To better understand the pathogenesis of this disease and to facilitate novel preclinical approaches, we previously developed a conditional mouse model of ARMS by faithfully recapitulating the genetic mutations observed in the human disease, i.e., activation of Pax3:Fkhr fusion gene with either p53 or Cdkn2a inactivation. In this report, we show that this model recapitulates the immunohistochemical profile and the rapid progression of the human disease. We show that Pax3:Fkhr expression increases during late preneoplasia but tumor cells undergoing metastasis are under apparent selection for Pax3:Fkhr expression. At a whole-genome level, a cross-species gene set enrichment analysis and metagene projection study showed that our mouse model is most similar to human ARMS when compared with other pediatric cancers. We have defined an expression profile conserved between mouse and human ARMS, as well as a Pax3:Fkhr signature, including the target gene, SKP2. We further identified 7 "druggable" kinases overexpressed across species. The data affirm the accuracy of this genetically engineered mouse model.


Assuntos
Rabdomiossarcoma Alveolar/genética , Rabdomiossarcoma Alveolar/patologia , Alelos , Animais , Inibidor p16 de Quinase Dependente de Ciclina/genética , Progressão da Doença , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/biossíntese , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Knockout , Proteínas de Fusão Oncogênica/biossíntese , Proteínas de Fusão Oncogênica/genética , Fator de Transcrição PAX3 , Fatores de Transcrição Box Pareados/biossíntese , Fatores de Transcrição Box Pareados/genética , Penetrância , Rabdomiossarcoma Alveolar/metabolismo , Ativação Transcricional , Proteína Supressora de Tumor p53/genética
20.
Am J Surg Pathol ; 33(5): 775-80, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19145202

RESUMO

PAX5 is a member of the paired box transcription factors involved in development and its expression has been well characterized among hematopoietic malignancies of B-cell lineage. Its expression has also been reported in a subset of neuroendocrine carcinomas, urothelial tumors, Merkel cell carcinoma, glioblastoma, and neuroblastoma cell lines. As such, we sought to assess it as a diagnostic marker in the evaluation of pediatric small round blue cell tumors. Tumors selected for evaluation included embryonal rhabdomyosarcoma (55 cases), alveolar rhabdomyosarcoma (ARMS) (51 cases), neuroblastoma (22 cases), Wilms tumor (18 cases), Ewing Family of Tumors (11 cases), lymphoblastic lymphoma (8 cases), hepatoblastoma (6 cases), and granulocytic sarcoma (3 cases) as either cores in a tissue microarray or whole mount sections. All cases were immunostained using an antibody directed toward PAX5 and immunoreactivity was scored semiquantitatively according to percentage of nuclear staining. As expected, all B-cell lymphoblastic lymphomas were strongly immunoreactive against PAX5. Additionally, all Wilms tumors showed staining of variable intensity, most intensely in the epithelial component. Of the rhabdomyosarcoma cases, 34 of 51 (67%) ARMS were immunoreactive whereas none of the 55 embryonal rhabdomyosarcoma cases stained. No other tumor type on the array was immunoreactive toward PAX5. Genetic information was available on 7 ARMS, 5 of which had characteristic translocations involving PAX genes, either t(2:13) or t(1;13). Of the translocation-positive cases, all showed nuclear reactivity toward PAX5, and both the translocation-negative cases did not. Possible explanations of PAX5 staining include aberrant expression of the PAX5 transcription factor, PAX5 expression in normal tissue at the time the tumors most closely recapitulates in development or crossreactivity with another member of the PAX family. PAX3 and PAX7 fusion genes characterize the majority of ARMS making crossreactivity with these proteins an attractive theory, and suggest that PAX5 immunoreactivity may be specific for translocation-positive ARMS. Further study in a larger series of rhabdomyosarcomas is warranted to assess the sensitivity and specificity of PAX5 immunoreactivity for the ARMS variant.


Assuntos
Fator de Transcrição PAX5/análise , Rabdomiossarcoma Alveolar/química , Adolescente , Neoplasias Ósseas/química , Criança , Pré-Escolar , Regulação Neoplásica da Expressão Gênica , Hepatoblastoma/química , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Neoplasias Renais/química , Neoplasias Hepáticas/química , Neuroblastoma/química , Fator de Transcrição PAX5/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Valor Preditivo dos Testes , Estudos Retrospectivos , Rabdomiossarcoma Alveolar/genética , Rabdomiossarcoma Alveolar/patologia , Rabdomiossarcoma Embrionário/química , Sarcoma de Ewing/química , Sarcoma Mieloide/metabolismo , Análise Serial de Tecidos , Translocação Genética , Tumor de Wilms/química
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