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1.
Gynecol Oncol Rep ; 54: 101426, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38881561

RESUMEN

•ESR1 gene amplification occurs in 7% of uterine carcinosarcoma.•The presence of ESR1 gene amplification in recurrent uterine carcinosarcoma may be targeted by aromatase inhibitors.•ESR1 gene amplification may be identified through immunohistochemical staining for estrogen receptor followed by fluorescence in situ hybridization or tumor targeted gene sequencing.

3.
Arch Pathol Lab Med ; 2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-38244086

RESUMEN

CONTEXT.­: The Nottingham Grading System (NGS) developed by Elston and Ellis is used to grade invasive breast cancer (IBC). Glandular (acinar)/tubule formation is a component of NGS. OBJECTIVE.­: To investigate the ability of pathologists to identify individual structures that should be classified as glandular (acinar)/tubule formation. DESIGN.­: A total of 58 hematoxylin-eosin photographic images of IBC with 1 structure circled were classified as tubules (41 cases) or nontubules (17 cases) by Professor Ellis. Images were sent as a PowerPoint (Microsoft) file to breast pathologists, who were provided with the World Health Organization definition of a tubule and asked to determine if a circled structure represented a tubule. RESULTS.­: Among 35 pathologists, the κ statistic for assessing agreement in evaluating the 58 images was 0.324 (95% CI, 0.314-0.335). The median concordance rate between a participating pathologist and Professor Ellis was 94.1% for evaluating 17 nontubule cases and 53.7% for 41 tubule cases. A total of 41% of the tubule cases were classified correctly by less than 50% of pathologists. Structures classified as tubules by Professor Ellis but often not recognized as tubules by pathologists included glands with complex architecture, mucinous carcinoma, and the "inverted tubule" pattern of micropapillary carcinoma. A total of 80% of participants reported that they did not have clarity on what represented a tubule. CONCLUSIONS.­: We identified structures that should be included as tubules but that were not readily identified by pathologists. Greater concordance for identification of tubules might be obtained by providing more detailed images and descriptions of the types of structures included as tubules.

4.
AMIA Jt Summits Transl Sci Proc ; 2020: 440-448, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32477665

RESUMEN

Precision oncology research seeks to derive knowledge from existing data. Current work seeks to integrate clinical and genomic data across cancer centers to enable impactful secondary use. However, integrated data reliability depends on the data curation method used and its systematicity. In practice, data integration and mapping are often done manually even though crucial data such as oncological diagnoses (DX) show varying accuracy and specificity levels. We hypothesized that mapping of text-form cancer DX to a standardized terminology (OncoTree) could be automated using existing methods (e.g. natural language processing (NLP) modules and application programming interfaces [APIs]). We found that our best-performing pipeline prototype was effective but limited by API development limitations (accurately mapped 96.2% of textual DX dataset to NCI Thesaurus (NCIt), 44.2% through NCIt to OncoTree). These results suggest the pipeline model could be viable to automate data curation. Such techniques may become increasingly more reliable with further development.

5.
J Gastrointest Oncol ; 10(4): 695-702, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31392050

RESUMEN

BACKGROUND: Exosomes are important mediators of intercellular communications and play pivotal roles in cancer progression, metastasis and chemoresistance. CD63 and CD9 are widely accepted exosomal markers. In patients with pancreatic ductal adenocarcinoma (PDAC), positive correlation between CD9 expression and overall survival (OS) was reported. CD63 expression was conserved in all patients with no reported prognostic significance. This study explored the prognostic significance of CD63 and CD9 expression using immunohistochemistry (IHC) in patients with PDAC of mixed racial background. METHODS: Between 2012 and 2016, 49 patients with PDAC had available tissues for CD63 and CD9 staining using IHC. Two pathologists independently scored the CD63 and CD9 expression. Staining intensity was graded from 1-3 and staining percentage was estimated in 10% increments. Mean Quick-score (Q-score) (Intensity X Percentage of staining) was calculated. RESULTS: The mean Q-score for CD63 and CD9 are higher in primary tumor from the pancreas compared to pancreatic tumor from metastatic sites (185 vs. 102, P=0.0002) and (48 vs. 20, P=0.0418) respectively. We fitted Cox proportion hazard regression models to investigate the impact of the covariates CD63 and CD9 on progression free survival (PFS) and OS. CD63 has significant impact on PFS (P=0.0135) and OS (P=0.003). The higher the CD63 Q-score, the longer the PFS and OS. CD9 doesn't have significant impact on PFS (P=0.5734) or OS (P=0.2682). The mean CD63 and CD9 Q-scores are slightly higher in African American (AA) compared to Caucasians (157 vs. 149, P=0.76) and (45 vs. 29, P=0.43) respectively. CONCLUSIONS: CD63 and CD9 expression is higher in primary tumor from the pancreas compared to pancreatic tumor from metastatic sites. There is correlation between CD63 expression (but not CD9 in this cohort) and PFS and OS. To our knowledge, this is the first study to show prognostic significance of CD63 expression in patients with PDAC using IHC. A trend of higher expression of CD63 and CD9 among AA compared to Caucasians was also noticed.

6.
JAMIA Open ; 2(3): 369-377, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31984369

RESUMEN

BACKGROUND: Structured diagnosis (DX) are crucial for secondary use of electronic health record (EHR) data. However, they are often suboptimally recorded. Our previous work showed initial evidence of variable DX recording patterns in oncology charts even after biopsy records are available. OBJECTIVE: We verified this finding's internal and external validity. We hypothesized that this recording pattern would be preserved in a larger cohort of patients for the same disease. We also hypothesized that this effect would vary across subspecialties. METHODS: We extracted DX data from EHRs of patients treated for brain, lung, and pancreatic neoplasms, identified through clinician-led chart reviews. We used statistical methods (i.e., binomial and mixed model regressions) to test our hypotheses. RESULTS: We found variable recording patterns in brain neoplasm DX (i.e., larger number of distinct DX-OR = 2.2, P < 0.0001, higher descriptive specificity scores-OR = 1.4, P < 0.0001-and much higher entropy after the BX-OR = 3.8 P = 0.004 and OR = 8.0, P < 0.0001), confirming our initial findings. We also found strikingly different patterns for lung and pancreas DX. Although both seemed to have much lower DX sequence entropy after the BX-OR = 0.198, P = 0.015 and OR = 0.099, P = 0.015, respectively compared to OR = 3.8 P = 0.004). We also found statistically significant differences between the brain dataset and both the lung (P < 0.0001) and pancreas (0.009

7.
Appl Immunohistochem Mol Morphol ; 27(1): 48-53, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-28549038

RESUMEN

Smooth muscle myosin heavy chain (SMMHC) is a major structural component of the contractile apparatus in smooth muscle cells. Even though it is considered a relatively specific marker for terminal smooth muscle cell differentiation, expression in other cell types such as follicular dendritic cells (FDCs) has rarely been reported. To determine whether SMMHC represents an effective FDC marker in lymphoid tissues, we compared the immunohistochemical results for SMMHC with those of the traditional FDC markers podoplanin (D2-40) and CD21. Paraffin sections of 44 lymphoid tissues were analyzed, including 31 cases of follicular hyperplasia, 6 cases of follicular lymphoma, 2 cases of peripheral T-cell lymphoma, 3 cases of diffuse large B-cell lymphoma arising in follicular lymphoma, 1 case of nodular sclerosis classical Hodgkin lymphoma, and 1 case of small lymphocytic lymphoma. There was no statistically significant difference between the number of SMMHC-positive and D2-40-positive or CD21 lymph nodes (P>0.05). The extent and intensity of SMMHC-positive FDCs were similar to those of D2-40-positive FDCs (P=0.127 and 0.733, respectively), but significantly lower compared with those of CD21 cells (P=0.009 and 0.00002, respectively). However, in contrast to CD21 which was also positive in some germinal center B cells, SMMHC expression was restricted to FDCs. Our results indicate that SMMHC is an excellent marker for FDCs and can be particularly helpful in demonstrating the underlying architecture in lymphoid processes.


Asunto(s)
Linfocitos B/metabolismo , Biomarcadores de Tumor/metabolismo , Células Dendríticas Foliculares/metabolismo , Ganglios Linfáticos/metabolismo , Linfoma Folicular/metabolismo , Miocitos del Músculo Liso/fisiología , Cadenas Pesadas de Miosina/metabolismo , Diferenciación Celular , Células Dendríticas Foliculares/patología , Humanos , Inmunohistoquímica , Ganglios Linfáticos/patología , Linfoma Folicular/diagnóstico , Linfoma Folicular/patología , Glicoproteínas de Membrana/metabolismo , Receptores de Complemento 3d/metabolismo
8.
J Gastrointest Oncol ; 9(3): 416-424, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29998006

RESUMEN

BACKGROUND: The correlation between DPYD*9A (c.85T>C) genotype and dihydropyrimidine dehydrogenase (DPD) deficiency clinical phenotype is controversial. Reference laboratories either did not perform DPYD*9A genotyping or have stopped DPYD*9A genotyping and limited genotyping to high-risk variants (DPYD*2A, DPYD*13 and DPYD*9B) only. This study explored DPYD*9A genotype and clinical phenotype correlation in patients with gastrointestinal (GI) malignancies treated with fluoropyrimidines. METHODS: Between 2011 and 2017, 67 patients with GI malignancies were genotyped for DPYD variants. Fluoropyrimidines-associated toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). Fisher's exact test was used for statistical analysis. RESULTS: DPYD variants were identified in 17 out of 67 (25%) patients. One patient was homozygous for DPYD*9A variant and one patient was double heterozygous for DPYD*9A and DPYD*9B variants. In patients with identified DPYD variants, 13/17 (76%) patients had DPYD*9A variant, 3/17 (18%) patients had DPYD*2A variant and 2/17 (12%) patient had DPYD*9B variant. Only patients genotyped prior to 2015 were genotyped for DPYD*9A variant (N=28). Of those, 13/28 patients (46%) had DPYD*9A variant. Grade 3-4 diarrhea was associated with DPYD*9A variant in patients treated with full dose fluoropyrimidines (P=0.0055). CONCLUSIONS: In our cohort, DPYD*9A variant was the most common diagnosed variant. The correlation between DPYD*9A genotype and DPD deficiency in clinical phenotype was noticeable in patients who received full dose fluoropyrimidines as they all experienced grade 3-4 toxicities (diarrhea).

9.
Hum Pathol ; 72: 180-190, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29170017

RESUMEN

The World Health Organization classification of lymphoma recommends the subdivision of follicular lymphoma (FL) into 3 grades (FL1-3) based on the average number of centroblasts per high-power field in the neoplastic follicles, but does not recognize a form of FL characterized by a predominance of large cleaved cells (centrocytes) without enough centroblasts to meet the World Health Organization criteria for FL3. We have classified such cases as follicular large cleaved cell lymphoma (FLC) and, herein, describe the pathologic and clinical features of 72 cases of this entity. The features of FLC include a follicular growth pattern with pale follicles at low magnification and frequent follicular and/or interfollicular fibrosis. Cytologically, the cells are predominantly large cleaved cells with moderately coarse to fine chromatin, absent or inconspicuous nucleoli, and small to moderate amounts of pale cytoplasm. The mean nuclear diameter of the large cleaved cells was 10.1µ, approximately twice that of small lymphocytes and similar to centroblasts. The t(14;18) was present in 83% of the cases, and a high proportion expressed BCL2 (84%), BCL6 (100%), and CD10 (88%) and had high Ki67 proliferation (81%). The clinical features of patients with FLC were similar to those with other types of FL, and survival was excellent with anthracycline-based chemotherapy plus rituximab. FLC is a variant of follicular lymphoma which should be recognized in future lymphoma classifications because the diagnosis of FLC may be important for the selection of therapy.


Asunto(s)
Linfocitos B/patología , Linfocitos/patología , Linfoma Folicular/patología , Rituximab/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Linfocitos B/efectos de los fármacos , Diagnóstico Diferencial , Femenino , Humanos , Linfocitos/efectos de los fármacos , Linfoma Folicular/diagnóstico , Linfoma Folicular/mortalidad , Masculino , Persona de Mediana Edad , Translocación Genética/genética
10.
Cell Cycle ; 17(3): 330-347, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29143560

RESUMEN

Fetal stem cells are a unique type of adult stem cells that have been suggested to be broadly multipotent with some features of pluripotency. Their clinical potential has been documented but their upgrade to full pluripotency could open up a wide range of cell-based therapies particularly suited for pediatric tissue engineering, longitudinal studies or disease modeling. Here we describe episomal reprogramming of mesenchymal stem cells from the human amnion to pluripotency (AM-iPSC) in chemically defined conditions. The AM-iPSC expressed markers of embryonic stem cells, readily formed teratomas with tissues of all three germ layers present and had a normal karyotype after around 40 passages in culture. We employed novel computational methods to determine the degree of pluripotency from microarray and RNA sequencing data in these novel lines alongside an iPSC and ESC control and found that all lines were deemed pluripotent, however, with variable scores. Differential expression analysis then identified several groups of genes that potentially regulate this variability in lines within the boundaries of pluripotency, including metallothionein proteins. By further studying this variability, characteristics relevant to cell-based therapies, like differentiation propensity, could be uncovered and predicted in the pluripotent stage.


Asunto(s)
Amnios/citología , Células Madre Pluripotentes Inducidas/citología , Biomarcadores/metabolismo , Forma de la Célula , Células Cultivadas , Redes Reguladoras de Genes , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Teratoma/patología , Transcripción Genética
11.
J Vis Exp ; (129)2017 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-29286443

RESUMEN

Autologous cell-based therapies got a step closer to reality with the introduction of induced pluripotent stem cells. Fetal stem cells, such as amniotic fluid and membrane mesenchymal stem cells, represent a unique type of undifferentiated cells with promise in tissue engineering and for reprogramming into iPSC for future pediatric interventions and stem cell banking. The protocol presented here describes an optimized procedure for extracting and culturing primary amniotic fluid and membrane mesenchymal stem cells and generating episomal induced pluripotent stem cells from these cells in fully chemically defined culture conditions utilizing human recombinant vitronectin and the E8 medium. Characterization of the new lines by applying stringent methods - flow cytometry, confocal imaging, teratoma formation and transcriptional profiling - is also described. The newly generated lines express markers of embryonic stem cells - Oct3/4A, Nanog, Sox2, TRA-1-60, TRA-1-81, SSEA-4 - while being negative for the SSEA-1 marker. The stem cell lines form teratomas in scid-beige mice in 6-8 weeks and the teratomas contain tissues representative of all three germ layers. Transcriptional profiling of the lines by submitting global expression microarray data to a bioinformatic pluripotency assessment algorithm deemed all lines pluripotent and therefore, this approach is an attractive alternative to animal testing. The new iPSC lines can readily be used in downstream experiments involving the optimization of differentiation and tissue engineering.


Asunto(s)
Líquido Amniótico/citología , Técnicas de Reprogramación Celular/métodos , Células Madre Pluripotentes Inducidas/citología , Animales , Diferenciación Celular/fisiología , Humanos , Ratones , Ratones SCID
12.
Pancreas ; 46(6): 782-788, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28609367

RESUMEN

OBJECTIVES: Exosomes are important mediators in intercellular communications and play a role in cancer progression and metastasis. Exosomal membranes are enriched in endosome-specific tetraspanins (CD9 and CD63). Here, we explored the expression of CD63 and CD9 utilizing immunohistochemistry in malignant and nonmalignant cells in 29 resected pancreatic specimens (RPSs) of mixed racial background. METHODS: The pathologic tissues (PTs) and adjacent normal tissues (ANTs) in each RPS were stained for CD63 and CD9. Two pathologists independently scored the expression of CD63 and CD9. Staining intensity was graded from 1 to 3. Staining percentage was estimated in 10% increments. An average Quick score (Q score) (intensity × percentage of staining) was calculated. Unpaired t test was used for statistical analysis. RESULTS: The mean multiplicative Q score for CD63 and CD9 expression is higher in PTs (209 and 72) compared with ANTs (154 and 24) (P = 0.0041, P = 0.0018), respectively. The Mean Q score for CD63 and CD9 expression is higher in the malignant PTs (231 and 85) compared with ANTs (129 and 25) (P < 0.0001 and P < 0.0124). CONCLUSIONS: Exosomal markers (CD63 and CD9) expression assessment using immunohistochemistry is feasible in RPS. The expression of CD63 and CD9 is higher in PTs and malignant PTs compared with their ANTs.


Asunto(s)
Biomarcadores de Tumor/análisis , Exosomas/química , Inmunohistoquímica , Neoplasias Pancreáticas/química , Tetraspanina 29/análisis , Tetraspanina 30/análisis , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Exosomas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Valor Predictivo de las Pruebas , Regulación hacia Arriba
13.
Cell Cycle ; 15(2): 234-49, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26654216

RESUMEN

Amniotic fluid stem cells (AFSC) represent an attractive potential cell source for fetal and pediatric cell-based therapies. However, upgrading them to pluripotency confers refractoriness toward senescence, higher proliferation rate and unlimited differentiation potential. AFSC were observed to rapidly and efficiently reacquire pluripotency which together with their easy recovery makes them an attractive cell source for reprogramming. The reprogramming process as well as the resulting iPSC epigenome could potentially benefit from the unspecialized nature of AFSC. iPSC derived from AFSC also have potential in disease modeling, such as Down syndrome or ß-thalassemia. Previous experiments involving AFSC reprogramming have largely relied on integrative vector transgene delivery and undefined serum-containing, feeder-dependent culture. Here, we describe non-integrative oriP/EBNA-1 episomal plasmid-based reprogramming of AFSC into iPSC and culture in fully chemically defined xeno-free conditions represented by vitronectin coating and E8 medium, a system that we found uniquely suited for this purpose. The derived AF-iPSC lines uniformly expressed a set of pluripotency markers Oct3/4, Nanog, Sox2, SSEA-1, SSEA-4, TRA-1-60, TRA-1-81 in a pattern typical for human primed PSC. Additionally, the cells formed teratomas, and were deemed pluripotent by PluriTest, a global expression microarray-based in-silico pluripotency assay. However, we found that the PluriTest scores were borderline, indicating a unique pluripotent signature in the defined condition. In the light of potential future clinical translation of iPSC technology, non-integrating reprogramming and chemically defined culture are more acceptable.


Asunto(s)
Reprogramación Celular , Células Madre Pluripotentes Inducidas/citología , Plásmidos/química , Transfección/métodos , Líquido Amniótico/citología , Líquido Amniótico/efectos de los fármacos , Antígenos de Superficie/genética , Antígenos de Superficie/metabolismo , Biomarcadores/metabolismo , Técnicas de Cultivo de Célula , Diferenciación Celular , Proliferación Celular , Medios de Cultivo/farmacología , Expresión Génica , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Antígeno Lewis X/genética , Antígeno Lewis X/metabolismo , Proteína Homeótica Nanog , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Plásmidos/metabolismo , Análisis por Matrices de Proteínas , Proteoglicanos/genética , Proteoglicanos/metabolismo , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Antígenos Embrionarios Específico de Estadio/genética , Antígenos Embrionarios Específico de Estadio/metabolismo
14.
Diagn Cytopathol ; 43(1): 40-4, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24554599

RESUMEN

Rosai-Dorfman disease (RDD), also known as "sinus histiocytosis with massive lymphadenopathy," only rarely involves the gastrointestinal (GI) tract. Therefore, this unusual site of presentation can be challenging for the pathologist. We present a case of RDD manifesting as a rectal submucosal mass associated with rectal bleeding in a 54 year old woman. The diagnosis was made on cytologic preparations obtained through endoscopic ultrasound guided fine needle aspiration (EUS-FNA) and subsequently confirmed by biopsy. To our knowledge, this is the first time extranodal RDD of the GI tract has been diagnosed by EUS-FNA. A review of previously published cases of GI RDD is presented to increase awareness of this exceptional presentation.


Asunto(s)
Histiocitosis Sinusal/patología , Recto/patología , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Femenino , Humanos , Persona de Mediana Edad
15.
Br J Haematol ; 166(2): 202-8, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24697285

RESUMEN

Few studies have examined the value of a mandatory second review of outside pathology material for haematological malignancies. Therefore, we compared diagnoses on biopsies referred to an academic medical centre to determine the rate and therapeutic impact of revised diagnoses resulting from a second review. We reviewed 1010 cases referred for lymphoma during 2009-2010. For each case, referral diagnosis and second review diagnosis were compared. Revised diagnoses were grouped into major and minor discrepancies and all major discrepancies were reviewed by a haematologist to determine the effect the diagnostic change would have on therapy. There was no change in diagnosis in 861 (85·2%) cases. In 149 (14·8%) cases, second review resulted in major diagnostic change, of which 131 (12·9%) would have resulted in a therapeutic change. The highest rates of revision were for follicular, high-grade B-cell, and T-cell lymphomas. We found higher rates of major discrepancy in diagnoses from non-academic centres (15·8%) compared to academic centres (8·5%; P = 0·022), and in excisional biopsies (17·9%) compared to smaller biopsies (9·6%; P = 0·0003). Mandatory review of outside pathology material prior to treatment of patients for lymphoma will identify a significant number of misclassified cases with a major change in therapy.


Asunto(s)
Errores Diagnósticos/estadística & datos numéricos , Linfoma/diagnóstico , Centros Médicos Académicos , Biopsia , Diagnóstico Diferencial , Humanos , Linfoma/patología , Linfoma/terapia , Nebraska , Atención al Paciente , Derivación y Consulta
16.
Br J Haematol ; 165(3): 382-91, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24506200

RESUMEN

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and "double-hit" DLBCL, with both MYC and BCL2 translocations has a poor prognosis. In this study, we investigated whether MYC and BCL2 protein expression in tissue would predict survival in DLBCL. The study included 106 cases of de novo DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or CHOP-like regimens. The results were validated on an independent cohort of 205 DLBCL patients. Patients with low expression of BCL2 (≤30%) and MYC (≤50%) had the best prognosis, whereas those with high BCL2 (>30%) and MYC (>50%) had the worst outcome. In multivariate analysis, the combination of the BCL2 and MYC was an independent predictor of overall survival (OS) and event-free survival (EFS) (P = 0·015 and P = 0·005, respectively). The risk of death was nine times greater for patients with high BCL2 and MYC compared to those with low expression. High BCL2 and MYC was a strong predictor of poor OS (P < 0·001) and EFS (P = 0·0017) in patients with the germinal centre B-cell (GCB) type, but not in the non-GCB type. In DLBCL, high co-expression of MYC and BCL2 was an independent predictor of poor survival, and could be used to stratify patients for risk-adapted therapies.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteínas Proto-Oncogénicas c-myc/biosíntesis , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Genes myc , Humanos , Inmunohistoquímica , Linfoma de Células B Grandes Difuso/genética , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-myc/genética , Rituximab , Análisis de Supervivencia , Resultado del Tratamiento , Vincristina/administración & dosificación
17.
Am J Clin Pathol ; 138(6): 877-83, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23161722

RESUMEN

The presence of the BRAF c.1799T>A V600E mutation was recently described in cases of hairy cell leukemia (HCL) but not in other common lymphomas. However, many uncommon subtypes of lymphoma have not been studied. We designed a BRAF pyrosequencing assay specific for the V600E mutation, which has a sensitivity of 5% and is applicable to paraffin-embedded tissue. DNA was sequenced in 9 cases of HCL; 6 cases of variant HCL; 10 cases each of nodal marginal zone lymphoma (NMZL), extranodal marginal zone lymphoma (ENMZL), posttransplantation lymphoproliferative disorder (PTLD), and large granular lymphocyte (LGL) proliferations; 11 cases of peripheral T-cell lymphoma (PTCL); and 12 cases of anaplastic large cell lymphoma (ALCL). All (100%) cases of HCL were positive for BRAF mutations. No mutations were identified in variant HCL, NMZL, ENMZL, PTLD, PTCL, ALCL, or LGL proliferations. Among lymphoproliferative disorders, BRAF mutations are restricted to HCL.


Asunto(s)
Leucemia de Células Pilosas/genética , Trastornos Linfoproliferativos/genética , Mutación Puntual/genética , Proteínas Proto-Oncogénicas B-raf/genética , Análisis de Secuencia de ADN/métodos , Adulto , Anciano , Anciano de 80 o más Años , Alelos , ADN de Neoplasias/química , ADN de Neoplasias/genética , Femenino , Humanos , Leucemia de Células Pilosas/patología , Trastornos Linfoproliferativos/patología , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Adulto Joven
18.
Blood ; 120(24): 4795-801, 2012 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-23086753

RESUMEN

The distribution of non-Hodgkin lymphoma (NHL) subtypes differs around the world but a systematic study of Latin America has not been done. Therefore, we evaluated the relative frequencies of NHL subtypes in Central and South America (CSA). Five expert hematopathologists classified consecutive cases of NHL from 5 CSA countries using the WHO classification and compared them to 400 cases from North America (NA). Among the 1028 CSA cases, the proportions of B- and T-cell NHL and the sex distribution were similar to NA. However, the median age of B-cell NHL in CSA (59 years) was significantly lower than in NA (66 years; P < .0001). The distribution of high-grade (52.9%) and low-grade (47.1%) mature B-cell NHL in CSA was also significantly different from NA (37.5% and 62.5%; P < .0001). Diffuse large B-cell lymphoma was more common in CSA (40%) than in NA (29.2%; P < .0001), whereas the frequency of follicular lymphoma was similar in Argentina (34.1%) and NA (33.8%), and higher than the rest of CSA (17%; P < .001). Extranodal NK/T-cell NHL was also more common in CSA (P < .0001). Our study provides new objective evidence that the distribution of NHL subtypes varies significantly by geographic region and should prompt epidemiologic studies to explain these differences.


Asunto(s)
Linfoma no Hodgkin/clasificación , Linfoma no Hodgkin/diagnóstico , Argentina/epidemiología , Brasil/epidemiología , Chile/epidemiología , Femenino , Guatemala/epidemiología , Humanos , Linfoma no Hodgkin/epidemiología , Masculino , Persona de Mediana Edad , Perú/epidemiología , Organización Mundial de la Salud
19.
J Clin Rheumatol ; 18(3): 138-41, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22426590

RESUMEN

Gout is a painful inflammatory arthropathy caused by crystallization of monosodium urate within the joints. We present the case of a patient with primary gout who had positive results of joint aspiration and synovial biopsy for monosodium urate crystals in the third metacarpophalangeal joint but false-negative results of dual-energy computed tomography.


Asunto(s)
Gota/diagnóstico por imagen , Articulación Metacarpofalángica/diagnóstico por imagen , Líquido Sinovial/metabolismo , Tomografía Computarizada por Rayos X/métodos , Ácido Úrico/metabolismo , Alopurinol/administración & dosificación , Artralgia/diagnóstico por imagen , Artralgia/etiología , Artralgia/metabolismo , Biopsia , Reacciones Falso Negativas , Gota/tratamiento farmacológico , Gota/metabolismo , Supresores de la Gota/administración & dosificación , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas
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