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1.
Oncotarget ; 7(14): 18036-49, 2016 Apr 05.
Article in English | MEDLINE | ID: mdl-26910115

ABSTRACT

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous group of aggressive lymphomas that can be classified into three molecular subtypes by gene expression profiling (GEP): GCB, ABC and unclassified. Immunohistochemistry-based cell of origin (COO) classification, as a surrogate for GEP, using three available immunohistochemical algorithms was evaluated in TMA-arranged tissue samples from 297 patients with de novo DLBCL treated by chemoimmunotherapy (R-CHOP and R-CHOP-like regimens). Additionally, the prognostic impacts of MYC, BCL2, IRF4 and BCL6 abnormalities detected by FISH, the relationship between the immunohistochemical COO classification and the immunohistochemical expression of MYC, BCL2 and pSTAT3 proteins and clinical data were evaluated. In our series, non-GCB DLBCL patients had significantly worse progression-free survival (PFS) and overall survival (OS), as calculated using the Choi, Visco-Young and Hans algorithms, indicating that any of these algorithms would be appropriate for identifying patients who require alternative therapies to R-CHOP. Whilst MYC abnormalities had no impact on clinical outcome in the non-GCB subtype, those patients with isolated MYC rearrangements and a GCB-DLBCL phenotype had worse PFS and therefore might benefit from novel treatment approaches.


Subject(s)
Lymphoma, Large B-Cell, Diffuse/classification , Lymphoma, Large B-Cell, Diffuse/drug therapy , Algorithms , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cohort Studies , Cyclophosphamide/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Humans , Immunohistochemistry , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/pathology , Middle Aged , Prednisone/administration & dosage , Retrospective Studies , Rituximab/administration & dosage , Survival Analysis , Vincristine/administration & dosage
2.
Blood ; 118(4): 1034-40, 2011 Jul 28.
Article in English | MEDLINE | ID: mdl-21633089

ABSTRACT

Diffuse large B-cell lymphoma (DLBCL) prognostication requires additional biologic markers. miRNAs may constitute markers for cancer diagnosis, outcome, or therapy response. In the present study, we analyzed the miRNA expression profile in a retrospective multicenter series of 258 DLBCL patients uniformly treated with chemoimmunotherapy. Findings were correlated with overall survival (OS) and progression-free survival (PFS). miRNA and gene-expression profiles were studied using microarrays in an initial set of 36 cases. A selection of miRNAs associated with either DLBCL molecular subtypes (GCB/ABC) or clinical outcome were studied by multiplex RT-PCR in a test group of 240 cases with available formalin-fixed, paraffin-embedded (FFPE) diagnostic samples. The samples were divided into a training set (123 patients) and used to derive miRNA-based and combined (with IPI score) Cox regression models in an independent validation series (117 patients). Our model based on miRNA expression predicts OS and PFS and improves upon the predictions based on clinical variables. Combined models with IPI score identified a high-risk group of patients with a 2-year OS and a PFS probability of < 50%. In summary, a precise miRNA signature is associated with poor clinical outcome in chemoimmunotherapy-treated DLBCL patients. This information improves upon IPI-based predictions and identifies a subgroup of candidate patients for alternative therapeutic regimens.


Subject(s)
Biomarkers, Tumor/genetics , Lymphoma, Large B-Cell, Diffuse/genetics , MicroRNAs/biosynthesis , Antineoplastic Agents/therapeutic use , Disease-Free Survival , Female , Gene Expression , Gene Expression Profiling , Humans , Immunohistochemistry , Immunotherapy , Kaplan-Meier Estimate , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Microarray Analysis , Middle Aged , Neoplasm Staging , Prognosis , Proportional Hazards Models , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Tissue Array Analysis
3.
Virchows Arch ; 444(5): 420-5, 2004 May.
Article in English | MEDLINE | ID: mdl-15067546

ABSTRACT

Lymphoepithelioma-like carcinoma of the bladder is an uncommon neoplasm, of which 49 cases have been described in the English literature, none of which has been studied for p53 protein expression. We studied three muscle-infiltrating cases of this tumor using immunohistochemical, in situ hybridization and polymerase chain reaction (PCR) methods. The three cases were positive for epithelial markers and negative for lymphoid antigens in the tumoral syncytial areas. The intensive infiltrate of small cells was negative for epithelial and positive for lymphoid markers. This population was mainly made up of cytotoxic T-lymphocytes, positive for TIA-1. p53 protein was intensely positive in more than 90% of the epithelial component nuclei, being negative in the lymphoid cells. PCR study did not show mutations on p53. Both lymphocytes and epithelium were negative for Epstein-Barr virus markers, such as the latent membrane protein and EBER (Epstein-Barr-encoded RNA). The prognosis was very good after radiotherapy and chemotherapy treatment, preserving the bladder despite the muscle infiltration. The presence of an intense cytotoxic T-lymphocyte population may be related to this good prognosis. Both aspects, p53 protein status and T-lymphoid population, had never been studied before in bladder lymphoepithelioma-like carcinoma.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Tumor Suppressor Protein p53/metabolism , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/therapy , DNA, Neoplasm/analysis , Disease-Free Survival , Epithelial Cells/metabolism , Epithelial Cells/pathology , Female , Genes, p53/physiology , Humans , In Situ Hybridization , Male , Polymerase Chain Reaction , Radiotherapy, Adjuvant , T-Lymphocytes, Cytotoxic/metabolism , T-Lymphocytes, Cytotoxic/pathology , Treatment Outcome , Tumor Suppressor Protein p53/genetics , Urinary Bladder/surgery , Urinary Bladder Neoplasms/therapy
4.
Actas dermo-sifiliogr. (Ed. impr.) ; 91(1/2): 1-8, ene. 2000. ilus, tab, graf
Article in Es | IBECS | ID: ibc-3905

ABSTRACT

Se estudiaron 43 pacientes diagnosticados de leishmaniasis cutánea (botón de Oriente) que acudieron a la consulta de dermatología del Hospital Virgen de la Salud entre enero de 1990 y diciembre de 1997. Recogimos los siguientes datos clínicos: sexo, edad, número de lesiones, tiempo de evolución, forma clínica, tamaño y localización. El diagnóstico fue por biopsia cutánea o hallazgo del microorganismo en frotis de la lesión. Encontramos una alta proporción de mujeres (70 %) con dos picos de frecuencia en la edad de los pacientes, uno en menores de 14 años (30 %) y el otro entre 61 y 75 años (30 %).La lesión era única en casi todos los pacientes (91 %). El tiempo de evolución de las lesiones presentaba dos picos de máxima frecuencia (6 y 12 meses). La localización era fundamentalmente en áreas fotoexpuestas: 75 % en cara y 19 % en extremidades. La forma clínica era polimorfa. La forma papulonodular eritematosa con costra en superficie fue la más observada, con un tamaño entre 0,3 y 5 cm. La infiltración intralesional de antimoniales pentavalentes fue el tratamiento más empleado, con resultado satisfactorio. Discutimos los resultados de este trabajo y los comparamos con otras revisiones publicadas (AU)


Subject(s)
Adolescent , Adult , Aged , Female , Child, Preschool , Infant , Male , Middle Aged , Child , Humans , Leishmaniasis, Cutaneous/diagnosis , Hand Dermatoses/diagnosis , Leg Dermatoses/diagnosis , Leishmaniasis, Cutaneous/drug therapy , Leishmaniasis, Cutaneous/etiology , Leishmaniasis, Cutaneous/pathology , Clinical Evolution , Biopsy , Itraconazole/pharmacology , Leishmania/pathogenicity , Injections, Intralesional , Age Distribution , Neck/parasitology , Antifungal Agents/pharmacology , Antifungal Agents/administration & dosage , Face/parasitology , Leg Dermatoses/parasitology , Hand Dermatoses/parasitology
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