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1.
Ann Pathol ; 43(6): 479-482, 2023 Nov.
Artículo en Francés | MEDLINE | ID: mdl-36906453

RESUMEN

Myoepithelial neoplasms of soft tissue represent a rare entity which has been described only recently when compared to salivary gland tumors with whom they share histopathological and molecular features. The most common locations are the superficial soft tissues of the limbs and limb girdles. However, they can rarely occur in the mediastinum, abdomen, bone, skin and visceral organs. Benign forms (myoepithelioma and mixed tumor) are more frequent than myoepithelial carcinoma and the latter mostly affects children and young adults. Diagnosis is mainly based on histology, which shows a proliferation of myoepithelial cells of variable morphology with or without glandular structures in a myxoid background, and immunohistochemistry, which shows co-expression of epithelial and myoepithelial markers. Molecular tests are not mandatory, but in selected cases FISH analysis can prove useful as about 50% of myoepitheliomas show EWSR1 (or rarely FUS) rearrangements and mixed tumors show PLAG1 rearrangements. Here, we present a case of a mixed tumor of the soft tissue occuring in the hand with expression of PLAG1 in immunohistochemistry.


Asunto(s)
Adenoma Pleomórfico , Mioepitelioma , Neoplasias de las Glándulas Salivales , Neoplasias de los Tejidos Blandos , Humanos , Adenoma Pleomórfico/patología , Biomarcadores de Tumor/análisis , Inmunohistoquímica , Mioepitelioma/diagnóstico , Mioepitelioma/química , Mioepitelioma/metabolismo , Neoplasias de las Glándulas Salivales/patología , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/patología
3.
Ann Pathol ; 41(6): 586, 2021 Nov.
Artículo en Francés | MEDLINE | ID: mdl-34481665

Asunto(s)
Esófago , Piel , Humanos
4.
Ann Pathol ; 39(2): 167-171, 2019 Apr.
Artículo en Francés | MEDLINE | ID: mdl-30554833

RESUMEN

Clear cells sarcomas (CCS) are exceptionally rare in the tongue, with, to our knowledge, only three previous reports in anglo-saxon literature. Through our case, we will discuss the differential diagnosis of clear cells tumors of the tongue and bring this tumour closer to the newly described entity of the gastrointestinal tract named "clear cells sarcoma-like gastrointestinal (SCCLGI)", recently renamed "gastrointestinal neuroectodermal tumour (GNET)". SCCLGI/GNET share morphological and molecular characteristics with SCC but had until then been observed only in the digestive tract. Our case could be a lingual localization of a SCCLGI/GNET. SCC and SCCLGI/GNET characteristic molecular profil involves EWSR1-ATF1 [t(12; 22) (q13; q12)] and EWSR1-CREB1 [t(2; 22) (q34; q12)] fusion genes, but it is not specific of these tumours.


Asunto(s)
Tumores Neuroectodérmicos/patología , Sarcoma de Células Claras/patología , Neoplasias de la Lengua/patología , Adulto , Diagnóstico Diferencial , Femenino , Neoplasias Gastrointestinales/patología , Humanos
5.
Clin Nucl Med ; 43(4): e118-e121, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29401145

RESUMEN

F-FDG PET/CT and MRI were performed in a 44-year-old woman to characterize a mass of the anterior tongue. MR images showed a voluminous mass, well circumscribed and enhanced heterogeneously after gadolinium chelates injection. There was an intense uptake on PET/CT. Pathological examination and molecular analysis revealed the diagnosis of clear cell sarcoma of the tongue. We present a case of clear cell sarcoma of the tongue, which includes imaging features. It is an extremely rare tumor, with only 3 cases previously reported in the literature.


Asunto(s)
Imagen por Resonancia Magnética , Tomografía Computarizada por Tomografía de Emisión de Positrones , Sarcoma de Células Claras/diagnóstico por imagen , Neoplasias de la Lengua/diagnóstico por imagen , Adulto , Femenino , Fluorodesoxiglucosa F18 , Humanos
6.
J Mol Diagn ; 18(2): 205-14, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26752307

RESUMEN

Personalized medicine has gained increasing importance in clinical oncology, and several clinically important biomarkers are implemented in routine practice. In an effort to guarantee high quality of molecular testing in France, three subsequent external quality assessment rounds were organized at the initiative of the National Cancer Institute between 2012 and 2014. The schemes included clinically relevant biomarkers for metastatic colorectal (KRAS, NRAS, BRAF, PIK3CA, microsatellite instability) and non-small cell lung cancer (EGFR, KRAS, BRAF, PIK3CA, ERBB2), and they represent the first multigene/multicancer studies throughout Europe. In total, 56 laboratories coordinated by 28 regional molecular centers participated in the schemes. Laboratories received formalin-fixed, paraffin-embedded samples and were asked to use routine methods for molecular testing to predict patient response to targeted therapies. They were encouraged to return results within 14 calendar days after sample receipt. Both genotyping and reporting were evaluated separately. During the three external quality assessment rounds, mean genotype scores were all above the preset standard of 90% for all biomarkers. Participants were mainly challenged in case of rare insertions or deletions. Assessment of the written reports showed substantial progress between the external quality assessment schemes on multiple criteria. Several essential elements such as the clinical interpretation of test results and the reason for testing still require improvement by continued external quality assessment education.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Colorrectales/genética , Ensayos de Aptitud de Laboratorios/normas , Neoplasias Pulmonares/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Colorrectales/patología , Francia , Pruebas Genéticas/normas , Técnicas de Genotipaje/normas , Humanos , Neoplasias Pulmonares/patología , Inestabilidad de Microsatélites , Factores de Tiempo
7.
Sci Transl Med ; 6(244): 244ra91, 2014 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-25009231

RESUMEN

Muscle-invasive bladder carcinoma (MIBC) constitutes a heterogeneous group of tumors with a poor outcome. Molecular stratification of MIBC may identify clinically relevant tumor subgroups and help to provide effective targeted therapies. From seven series of large-scale transcriptomic data (383 tumors), we identified an MIBC subgroup accounting for 23.5% of MIBC, associated with shorter survival and displaying a basal-like phenotype, as shown by the expression of epithelial basal cell markers. Basal-like tumors presented an activation of the epidermal growth factor receptor (EGFR) pathway linked to frequent EGFR gains and activation of an EGFR autocrine loop. We used a 40-gene expression classifier derived from human tumors to identify human bladder cancer cell lines and a chemically induced mouse model of bladder cancer corresponding to human basal-like bladder cancer. We showed, in both models, that tumor cells were sensitive to anti-EGFR therapy. Our findings provide preclinical proof of concept that anti-EGFR therapy can be used to target a subset of particularly aggressive MIBC tumors expressing basal cell markers and provide diagnostic tools for identifying these tumors.


Asunto(s)
Receptores ErbB/antagonistas & inhibidores , Terapia Molecular Dirigida , Músculos/patología , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/terapia , Adulto , Anciano , Anciano de 80 o más Años , Animales , Comunicación Autocrina/efectos de los fármacos , Butilhidroxibutilnitrosamina , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Receptores ErbB/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Factor Nuclear 3-alfa del Hepatocito/metabolismo , Humanos , Queratinas/metabolismo , Masculino , Ratones , Persona de Mediana Edad , Músculos/efectos de los fármacos , Invasividad Neoplásica , Fenotipo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Análisis de Supervivencia , Transcriptoma/genética , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/genética
8.
PLoS One ; 7(12): e48993, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23272046

RESUMEN

TP53 and FGFR3 mutations are the most common mutations in bladder cancers. FGFR3 mutations are most frequent in low-grade low-stage tumours, whereas TP53 mutations are most frequent in high-grade high-stage tumours. Several studies have reported FGFR3 and TP53 mutations to be mutually exclusive events, whereas others have reported them to be independent. We carried out a meta-analysis of published findings for FGFR3 and TP53 mutations in bladder cancer (535 tumours, 6 publications) and additional unpublished data for 382 tumours. TP53 and FGFR3 mutations were not independent events for all tumours considered together (OR = 0.25 [0.18-0.37], p = 0.0001) or for pT1 tumours alone (OR = 0.47 [0.28-0.79], p = 0.0009). However, if the analysis was restricted to pTa tumours or to muscle-invasive tumours alone, FGFR3 and TP53 mutations were independent events (OR = 0.56 [0.23-1.36] (p = 0.12) and OR = 0.99 [0.37-2.7] (p = 0.35), respectively). After stratification of the tumours by stage and grade, no dependence was detected in the five tumour groups considered (pTaG1 and pTaG2 together, pTaG3, pT1G2, pT1G3, pT2-4). These differences in findings can be attributed to the putative existence of two different pathways of tumour progression in bladder cancer: the CIS pathway, in which FGFR3 mutations are rare, and the Ta pathway, in which FGFR3 mutations are frequent. TP53 mutations occur at the earliest stage of the CIS pathway, whereas they occur would much later in the Ta pathway, at the T1G3 or muscle-invasive stage.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Mutación , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Proteína p53 Supresora de Tumor/genética , Neoplasias de la Vejiga Urinaria/genética , Progresión de la Enfermedad , Femenino , Genes p53 , Humanos , Masculino , Oncología Médica/métodos , Prevalencia
9.
J Pathol ; 227(3): 315-24, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22422578

RESUMEN

The gene cyclin-dependent kinase inhibitor 2A (CDKN2A) is frequently inactivated by deletion in bladder carcinoma. However, its role in bladder tumourigenesis remains unclear. We investigated the role of CDKN2A deletion in urothelial carcinogenesis, as a function of FGFR3 mutation status, a marker for one of the two pathways of bladder tumour progression, the Ta pathway. We studied 288 bladder carcinomas: 177 non-muscle-invasive (123 Ta, 54 T1) and 111 muscle-invasive (T2-4) tumours. CDKN2A copy number was determined by multiplex ligation-dependent probe amplification, and FGFR3 mutations by SNaPshot analysis. FGFR3 mutation was detected in 124 tumours (43.1%) and CDKN2A homozygous deletion in 56 tumours (19.4%). CDKN2A homozygous deletion was significantly more frequent in FGFR3-mutated tumours than in wild-type FGFR3 tumours (p = 0.0015). This event was associated with muscle-invasive tumours within the FGFR3-mutated subgroup (p < 0.0001) but not in wild-type FGFR3 tumours. Similar findings were obtained for an independent series of 101 bladder carcinomas. The impact of CDKN2A deletions on recurrence-free and progression-free survival was then analysed in 89 patients with non-muscle-invasive FGFR3-mutated tumours. Kaplan-Meier survival analysis showed that CDKN2A losses (hemizygous and homozygous) were associated with progression (p = 0.0002), but not with recurrence, in these tumours. Multivariate Cox regression analysis identified CDKN2A loss as a predictor of progression independent of stage and grade. These findings highlight the crucial role of CDKN2A loss in the progression of non-muscle-invasive FGFR3-mutated bladder carcinomas and provide a potentially useful clinical marker for adapting the treatment of such tumours, which account for about 50% of cases at initial clinical presentation.


Asunto(s)
Carcinoma/genética , Eliminación de Gen , Genes p16 , Homocigoto , Mutación , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Neoplasias de la Vejiga Urinaria/genética , Carcinoma/enzimología , Carcinoma/mortalidad , Carcinoma/secundario , Distribución de Chi-Cuadrado , Análisis Mutacional de ADN , Supervivencia sin Enfermedad , Francia , Dosificación de Gen , Predisposición Genética a la Enfermedad , Humanos , Estimación de Kaplan-Meier , Análisis Multivariante , Clasificación del Tumor , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Fenotipo , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Tiempo , Neoplasias de la Vejiga Urinaria/enzimología , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología
10.
BMC Cancer ; 11: 323, 2011 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-21801386

RESUMEN

BACKGROUND: Primary leiomyosarcoma of the seminal vesicle is exceedingly rare. CASE PRESENTATION: We report a case of a 59-year-old man with tumour detected by rectal symptoms and ultrasonography. Computed tomography and magnetic resonance imaging suggested an origin in the right seminal vesicle. Transperineal biopsy of the tumour revealed leiomyosarcoma. A radical vesiculo-prostactectomy with bilateral pelvic lymphadenectomy was performed. Pathological examination showed a grade 2 leiomyosarcoma of the seminal vesicle. The patient received adjuvant radiotherapy. He developed distant metastases 29 months after diagnosis, and received chemotherapy. Metastatic disease was controlled by second-line gemcitabine-docetaxel combination. Fifty-one months after diagnosis of the primary tumour, and 22 months after the first metastases, the patient is alive with excellent performance status, and multiple asymptomatic stable lung and liver lesions. CONCLUSIONS: We report the eighth case of primary leiomyosarcoma of the seminal vesicle and the first one with a so long follow-up.


Asunto(s)
Neoplasias de los Genitales Masculinos/diagnóstico , Leiomiosarcoma/diagnóstico , Vesículas Seminales/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Docetaxel , Neoplasias de los Genitales Masculinos/terapia , Humanos , Leiomiosarcoma/terapia , Neoplasias Hepáticas/prevención & control , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Prostatectomía , Radioterapia Adyuvante , Taxoides/administración & dosificación , Resultado del Tratamiento , Gemcitabina
11.
BMC Med Genomics ; 3: 59, 2010 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-21162720

RESUMEN

BACKGROUND: Germline mutations in the folliculin (FLCN) gene are associated with the development of Birt-Hogg-Dubé syndrome (BHDS), a disease characterized by papular skin lesions, a high occurrence of spontaneous pneumothorax, and the development of renal neoplasias. The majority of renal tumors that arise in BHDS-affected individuals are histologically similar to sporadic chromophobe renal cell carcinoma (RCC) and sporadic renal oncocytoma. However, most sporadic tumors lack FLCN mutations and the extent to which the BHDS-derived renal tumors share genetic defects associated with the sporadic tumors has not been well studied. METHODS: BHDS individuals were identified symptomatically and FLCN mutations were confirmed by DNA sequencing. Comparative gene expression profiling analyses were carried out on renal tumors isolated from individuals afflicted with BHDS and a panel of sporadic renal tumors of different subtypes using discriminate and clustering approaches. qRT-PCR was used to confirm selected results of the gene expression analyses. We further analyzed differentially expressed genes using gene set enrichment analysis and pathway analysis approaches. Pathway analysis results were confirmed by generation of independent pathway signatures and application to additional datasets. RESULTS: Renal tumors isolated from individuals with BHDS showed distinct gene expression and cytogenetic characteristics from sporadic renal oncocytoma and chromophobe RCC. The most prominent molecular feature of BHDS-derived kidney tumors was high expression of mitochondria-and oxidative phosphorylation (OXPHOS)-associated genes. This mitochondria expression phenotype was associated with deregulation of the PGC-1α-TFAM signaling axis. Loss of FLCN expression across various tumor types is also associated with increased nuclear mitochondrial gene expression. CONCLUSIONS: Our results support a genetic distinction between BHDS-associated tumors and other renal neoplasias. In addition, deregulation of the PGC-1α-TFAM signaling axis is most pronounced in renal tumors that harbor FLCN mutations and in tumors from other organs that have relatively low expression of FLCN. These results are consistent with the recently discovered interaction between FLCN and AMPK and support a model in which FLCN is a regulator of mitochondrial function.


Asunto(s)
Síndrome de Birt-Hogg-Dubé/genética , Genes Mitocondriales , Neoplasias Renales/genética , Regulación hacia Arriba , Adenoma Oxifílico/genética , Carcinoma de Células Renales/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Proteínas Mitocondriales/metabolismo , Fosforilación Oxidativa , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Proteínas Proto-Oncogénicas/genética , Transducción de Señal , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/genética
12.
Eur Urol ; 57(4): 699-707, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19428174

RESUMEN

BACKGROUND: Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) are highly prevalent in aging men and are strongly linked. Alpha1-blockers such as alfuzosin are effective monotherapies for LUTS. Phosphodiesterase type 5 (PDE5) inhibitors such as tadalafil are the first-line treatment for ED. Both drugs act by two different mechanisms of action on common urogenital target organs and, thus, may have additive effects. OBJECTIVES: We evaluated in vitro the effects of alfuzosin, tadalafil, and the combination of both on human detrusor and prostatic smooth muscle. DESIGN, SETTING, AND PARTICIPANTS: Prostatic and bladder tissue were obtained from patients (n=20 and n=17, respectively) undergoing cystoprostatectomy for bladder cancer. MEASUREMENTS: In organ baths, isolated prostatic strips and isolated bladder strips were incubated with vehicle, tadalafil (10⁻6 M and 10⁻5 M), alfuzosin (3×10⁻8 M or 10⁻6 M and 10⁻5 M) or a combination. Concentration-response curves (CRCs) to norepinephrine were generated on prostatic strips and detrusor strips precontracted with carbachol. Strips were also submitted to electrical field stimulation (EFS). RESULTS AND LIMITATIONS: When alfuzosin and tadalafil were combined, the maximal relaxation to norepinephrine on carbachol-precontracted detrusor strips was significantly increased compared with tadalafil alone, and EFS-induced detrusor contractions were better inhibited compared with each compound alone. Tadalafil significantly inhibited norepinephrine-induced prostatic strip contractions by reducing the maximal effect, whereas alfuzosin shifted the CRC of norepinephrine to the right. Combining both tadalafil and alfuzosin resulted in a greater relaxant effect. Likewise, the combination was more effective at reducing EFS-induced contractions compared with each compound alone. CONCLUSIONS: The combination of alfuzosin and tadalafil exerts an additive effect of inhibiting adrenergic smooth muscle tone of prostatic tissue and EFS-induced detrusor contractions and conversely, of enhancing adrenergic relaxation of detrusor precontracted with carbachol. These experiments provide experimental support for the clinical investigation of the combination of α1-blockers and PDE5 inhibitors in the treatment of LUTS.


Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Carbolinas/farmacología , Relajación Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Inhibidores de Fosfodiesterasa 5/farmacología , Próstata/efectos de los fármacos , Quinazolinas/farmacología , Vejiga Urinaria/efectos de los fármacos , Agonistas alfa-Adrenérgicos/farmacología , Anciano , Carbacol/farmacología , Agonistas Colinérgicos/farmacología , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Estimulación Eléctrica , Humanos , Técnicas In Vitro , Masculino , Norepinefrina/farmacología , Tadalafilo
13.
Ann Pathol ; 29(5): 428-30, 2009 Oct.
Artículo en Francés | MEDLINE | ID: mdl-20004849

RESUMEN

We report the case of a 48-year-old female patient who had a Crohn's disease treated by corticosteroids. The patient developed severe cardiac failure, which was refractory to treatment with inotropic agents. At necropsy, examination of the heart revealed myocardial abscesses. On microscopic study, we diagnosed an aspergillar myocarditis. Aspergillar myocarditis is a rare and fatal localisation in disseminated aspergillosis. Diagnosis is difficult and treatment, usually initiated late, is ineffective.


Asunto(s)
Aspergilosis/patología , Cardiomiopatías/microbiología , Resultado Fatal , Femenino , Humanos , Persona de Mediana Edad
14.
Cancer Res ; 69(21): 8256-64, 2009 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-19843858

RESUMEN

Urothelial carcinoma of the renal pelvis is a deadly disease with an unclear tumorigenic mechanism. We conducted gene expression profiling on a set of human tumors of this type and identified a phosphatidylinositol 3-kinase (PI3K)/AKT activation expression signature in 76.9% (n = 13) of our samples. Sequence analysis found both activating mutations of PIK3CA (13.6%, n = 22) and loss of heterozygosity at the PTEN locus (25%, n = 8). In contrast, none of the other subtypes of kidney neoplasms (e.g., clear-cell renal cell carcinoma) harbored PIK3CA mutations (n = 87; P < 0.001). Immunohistochemical analysis of urothelial carcinoma samples found loss of PTEN protein expression (36.4%, n = 11) and elevation of phosphorylated mammalian target of rapamycin (mTOR; 63.6%, n = 11). To confirm the role of the PI3K/AKT pathway in urothelial carcinoma, we generated mice containing biallelic inactivation of Pten in the urogenital epithelia. These mice developed typical renal pelvic urothelial carcinomas, with an incidence of 57.1% in mice older than 1 year. Laser capture microdissection followed by PCR confirmed the deletion of Pten exons 4 and 5 in the animal tumor cells. Immunohistochemical analyses showed increased phospho-mTOR and phospho-S6K levels in the animal tumors. Renal lymph node metastases were found in 15.8% of the animals with urothelial carcinoma. In conclusion, we identified and confirmed an important role for the PI3K/AKT pathway in the development of urothelial carcinoma and suggested that inhibitors of this pathway (e.g., mTOR inhibitor) may serve as effective therapeutic agents.


Asunto(s)
Neoplasias Renales/patología , Pelvis Renal/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Papilar/genética , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Femenino , Perfilación de la Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Integrasas/metabolismo , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Pelvis Renal/metabolismo , Rayos Láser , Pérdida de Heterocigocidad , Masculino , Ratones , Ratones Transgénicos , Microdisección , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosfohidrolasa PTEN/fisiología , Fosfatidilinositol 3-Quinasas/genética , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Quinasas S6 Ribosómicas 70-kDa/genética , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Serina-Treonina Quinasas TOR , Neoplasias de la Vejiga Urinaria/genética
15.
J Clin Oncol ; 27(17): 2809-15, 2009 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-19380452

RESUMEN

PURPOSE The indications of adjuvant chemotherapy for patients with estrogen receptor (ER) -positive breast cancer are controversial. We analyzed the predictive value of Ki67, HER2, and progesterone receptor (PR) expression for the efficacy of docetaxel in patients with ER-positive, node-positive breast cancer. PATIENTS AND METHODS Expression of Ki67, HER2, and PR was measured by immunohistochemistry in tumor samples from 798 patients with ER-positive breast cancer who participated in PACS01, a randomized trial that evaluated the efficacy of docetaxel. Risk reduction was evaluated using a Cox model adjusted for age, tumor size, nodal involvement, treatment arm, and biomarkers. The predictive value of biomarkers was assessed by an interaction test. Disease-free survival (DFS) was the primary end point. Results Ki67, HER2, and PR were expressed in 21%, 9%, and 62% of samples, respectively. Hazard ratios for relapse associated with docetaxel were 0.51 (95% CI, 0.26 to 1.01) in ER-positive/Ki67-positive tumors and 1.03 (95% CI, 0.69 to 1.55) in ER-positive/Ki67-negative tumors (ratio for interaction: 0.53; 95% CI, 0.24 to 1.16; P = .11). Five-year DFS rates were 81% (95% CI, 76% to 86%) and 84% (95% CI, 75% to 93%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with docetaxel and 81% (95% CI, 76% to 86%) and 62% (95% CI, 52% to 72%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with fluorouracil, epirubicin, and cisplatin. No trend for interaction was observed between docetaxel and HER2 (ratio for interaction: 0.83; 95% CI, 0.35 to 1.94; P = .66), nor between docetaxel and PR (ratio for interaction: 0.89; 95% CI, 0.47 to 1.66; P = .71). CONCLUSION Ki67 expression identifies a subset of patients with ER-positive breast cancer who could be sensitive to docetaxel treatment in the adjuvant setting.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Antígeno Ki-67/metabolismo , Taxoides/uso terapéutico , Adulto , Anciano , Antineoplásicos Hormonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Supervivencia sin Enfermedad , Docetaxel , Epirrubicina/uso terapéutico , Femenino , Humanos , Antígeno Ki-67/genética , Metástasis Linfática , Persona de Mediana Edad , Pronóstico , Receptores de Estrógenos/metabolismo , Resultado del Tratamiento
16.
Histol Histopathol ; 24(4): 425-35, 2009 04.
Artículo en Inglés | MEDLINE | ID: mdl-19224445

RESUMEN

OBJECTIVE: The prognostic significance of microvessel density in ovarian cancer is still a matter of debate. Classically, the degree of vascularisation is assessed in areas of high vascular density (hot spots), considered as regions of increased probability of metastasis. Since ovarian tumours have a particular progression and dissemination behaviour, vascularisation outside hot spots may also contribute to their evolution. METHODS: In the present study, the degree of tumour vascularisation was estimated both in whole histogical sections and in hot spots, in 235 patients with ovarian carcinoma, using fully automatic image analysis methods. Six parameters were estimated: mean microvessel density (MVD) and mean microvessel surface fraction (MSP) on the whole section, mean and maximum values of MVD and MSP inside hot spots (MVDHS1, MSPHS1 and MVDHS2, MSPHS2). Relationships between vascular parameters and clinicopathologic features were analysed. RESULTS: In stage III-IV patients multivariate analysis showed that stage IV disease (hazards ratio (HR)=1.72, p=0.001), post-surgical residual disease 1cm (HR=2.86, p<0.001), upper MVD tercile (HR=1.45, p<0.022) and medial MVDHS1 tercile (HR=1.36, p=0.060) retained an independent prognostic value upon overall survival. CONCLUSION: Our results suggest that quantification of blood vessels, both on the whole histological section and in hot spots might be helpful in evaluating prognosis in advanced ovarian carcinomas.


Asunto(s)
Adenocarcinoma/irrigación sanguínea , Adenocarcinoma/mortalidad , Neovascularización Patológica/mortalidad , Neoplasias Ováricas/irrigación sanguínea , Neoplasias Ováricas/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Microvasos/patología , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neovascularización Patológica/patología , Neoplasias Ováricas/patología , Pronóstico
17.
J Sex Med ; 6(3): 836-47, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19143907

RESUMEN

INTRODUCTION: Phosphodiesterase 5 inhibitors (PDE5) such as sildenafil are first-line treatment for erectile dysfunction (ED). Alpha1 (alpha1)-adrenoceptor antagonists such as doxazosin are indicated for the treatment of patients with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). ED and LUTS/BPH are conditions that are often associated. Accordingly, alpha1-adrenoceptor antagonists and PDE5 inhibitors will be often prescribed in real life setting together. AIM: To evaluate the effects of the combination of sildenafil and doxazosin on human cavernosal and prostatic tissue. METHODS: Prostatic and erectile tissues were obtained from nine to 12 patients, respectively. Patients underwent cystoprostatectomy for infiltrating bladder cancer or penile surgery for penile implant, congenital curvature or Peyronie's disease. MAIN OUTCOME MEASURES: In organ baths, prostatic and cavernosal strips were submitted to either concentration-response curves (CRC) to phenylephrine (Phe) or norepinephrine (NE), respectively, in presence of vehicle, sildenafil (10(-6) M, 10(-5) M), doxazosin (10(-8) M, 3.10(-8) M, or 10(-7) M), or a combination of both. Continuous electrical field stimulation (EFS; 32 Hz, 5 ms, 5 seconds, 300 mA) was performed on prostatic strips which were incubated with sildenafil 10(-6) M or vehicle before the successive addition of doxazosin (10(-7) M, 10(-6) M) or vehicle. Cavernosal strips were pre-incubated with doxazosin (10(-9) M, 10(-8) M) or vehicle, then CRC to sildenafil were constructed on NE (3.10(-6) M) precontracted cavernosal strips. RESULTS: Combination of sildenafil and doxazosin exerted a greater relaxing effect on CRC to Phe or NE compared with each compound alone in both tissues. Sildenafil significantly enhanced the relaxing effect of doxazosin on EFS-induced contractions in prostatic strips. Doxazosin significantly increased the ability of sildenafil to inhibit NE-induced contractions in cavernosal strips. CONCLUSIONS: Sildenafil and doxazosin reduced adrenergic tone of prostatic and cavernosal smooth muscle and their combination provided a significant benefit when targeting relaxation of both tissues. These experiments provide support for further clinical evaluation of the sildenafil and doxazosin combination in ED patients with LUTS/BPH.


Asunto(s)
Antagonistas Adrenérgicos alfa/farmacología , Doxazosina/farmacología , Disfunción Eréctil/tratamiento farmacológico , Relajación Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Pene/metabolismo , Inhibidores de Fosfodiesterasa/uso terapéutico , Piperazinas/uso terapéutico , Próstata/efectos de los fármacos , Sulfonas/uso terapéutico , Antagonistas Adrenérgicos alfa/farmacocinética , Adulto , Doxazosina/farmacocinética , Combinación de Medicamentos , Disfunción Eréctil/diagnóstico , Humanos , Masculino , Erección Peniana , Inhibidores de Fosfodiesterasa 5 , Inhibidores de Fosfodiesterasa/farmacología , Piperazinas/administración & dosificación , Purinas/administración & dosificación , Purinas/uso terapéutico , Citrato de Sildenafil , Sulfonas/administración & dosificación
18.
Am J Surg Pathol ; 32(5): 656-70, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18344867

RESUMEN

We report clinicopathologic features of a large series of renal translocation carcinomas from a multicentric study. Diagnosis was performed by cytogenetic examination of fresh material and/or by immunochemistry with antibodies directed against the C-terminal part of transcription factor E3 (TFE3) and native transcription factor EB (TFEB) proteins. Clinical data, follow-up, and histologic features were assessed. Antibodies against CK7, CD10, vimentin, epithelial membrane antigen, AE1-AE3, E-cadherin, alpha-methylacyl-coenzyme A racemase, melan A, and HMB45 were tested on tissue microarrays. Whole-genome microarray expression profiling was performed on 4 tumors. Twenty-nine cases were diagnosed as TFE3 and 2 as TFEB renal translocation carcinomas, including 13 males and 18 females, mean age 24.6 years. Two patients had a previous history of chemotherapy and 1 had a history of renal failure. Mean size of the tumor was 6.9 cm. Thirteen cases were > or = pT3 stage. Twelve cases were N+ or M+. Mean follow-up was 29.5 months. Three patients presented metastases and 5 have died. Mixed papillary and nested patterns with clear and/or eosinophilic cells represented the most consistent histologic appearance, with common foci of calcifications regardless of the type of translocation. Using a 30 mn incubation at room temperature, TFE3 immunostainings were positive in only 82% of our TFE3 translocation carcinomas. Both TFE3 and TFEB renal translocation carcinomas expressed CD10 and alpha-methylacyl-coenzyme A racemase in all cases. An expression of E-cadherin was observed in two-third of cases. Cytokeratins were expressed in less than one-third of cases. Melanocytic markers were expressed at least weakly in all cases except two. Unsupervised clustering on the basis of the gene expression profiling indicated a distinct subgroup of tumors. TRIM 63 glutathione S-transferase A1 and alanyl aminopeptidase are the main differentially expressed genes for this group of tumors. Our results suggest that these differentially expressed genes may serve as novel diagnostic or prognostic markers.


Asunto(s)
Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Perfilación de la Expresión Génica , Neoplasias Renales/genética , Neoplasias Renales/patología , Translocación Genética , Adolescente , Adulto , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/análisis , Biomarcadores de Tumor/análisis , Carcinoma de Células Renales/química , Niño , Análisis Citogenético , Femenino , Regulación Neoplásica de la Expresión Génica , Genoma , Humanos , Lactante , Neoplasias Renales/química , Masculino , Proteínas de Neoplasias/análisis , Nefrectomía , Análisis de Matrices Tisulares
19.
J Urol ; 178(4 Pt 1): 1184-8; discussion 1188, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17698122

RESUMEN

PURPOSE: We evaluated the results, accuracy and clinical incidence of our standard procedure of percutaneous biopsy for solid renal masses. MATERIALS AND METHODS: From March 1999 to April 2005, 119 percutaneous core biopsies of renal masses were performed. Biopsies were proposed when there was no formal evidence for a carcinoma diagnosis on computerized tomography. RESULTS: Benign lesions were diagnosed in 24 biopsies (20.1%), including oncocytoma in 13, angiomyolipoma in 5 and chronic pyelonephritis in 5. Malignancy was identified in 70 biopsies (58.8%), including 57 renal carcinomas (conventional renal cell in 41, papillary in 12 and chromophobe in 4), 4 transitional cell carcinomas, 8 metastases and 1 lymphoma. For 25 biopsies (21%) no accurate diagnosis was possible, including 12 that showed inflammatory tissue and 13 with normal or necrotic tissue. These inconclusive biopsies prompted repeat biopsy in 13 patients, in whom a total of 11 malignant lesions were diagnosed. A total of 64 nephrectomies were performed with a biopsy accuracy for histopathological tumor type and Fuhrman nuclear grade of 86% and 46%, respectively. A period of watchful waiting was proposed for 31 patients (34.2%) and no renal malignancies were found. Computerized tomography showed stabilization or disappearance of the initial renal mass. CONCLUSIONS: Percutaneous renal tumor biopsies are safe, cost-effective and often conclusive for an acute histological diagnosis. This procedure could be decisive for choosing the optimal treatment, particularly to avoid nephrectomy for benign lesions. Biopsies should not be considered a routine procedure but they could be indicated when there is a lack of radiological evidence in elective patients.


Asunto(s)
Biopsia , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Riñón/patología , Nefrostomía Percutánea , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/cirugía , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Riñón/diagnóstico por imagen , Enfermedades Renales/diagnóstico por imagen , Enfermedades Renales/patología , Enfermedades Renales/cirugía , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
20.
Eur J Radiol ; 60(2): 243-9, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16962279

RESUMEN

OBJECTIVE: Aschoff's center of proliferation (ACP), poses significant problems of differential diagnosis both in imagery and histology with infiltrating carcinoma. Up to now the criteria of Tabar and Dean (classical criteria) are considered as diagnostically relevant. MATERIAL: A retrospective study of 113 cases, enabled us to study their clinical, radiological and histological aspects. RESULTS: The ACP is a subclinical and seldom palpable entity (12%). The radiological signs of ACP are quite variable. The classical criteria lack specificity and are observed only in 48% of our stellate images. Whereas the frequency of microcalcifications is high (58.5% of the cases), their presence and their type are not predictive of an associated malignancy. The echographic diagnosis of ACP could be made in 55% of the cases but the echographic semiology lacked specificity. We noticed an associated atypical epithelial hyperplasia in 28.5% of the cases, intraductal or lobular in situ carcinoma in 9% and/or a ductal invasive carcinoma in 2% of the cases. Neither tumor size, age of the patients, nor any radiological signs were predictive of such an association. CONCLUSIONS: The classical criteria are not completely reliable and are observed only in half of our stellate images, whereas microcalcifications are often present but are not predictive of an associated malignancy.


Asunto(s)
Adenocarcinoma/patología , Neoplasias de la Mama/patología , Mama/patología , Carcinoma in Situ/patología , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/patología , Adenocarcinoma/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico por imagen , Calcinosis/diagnóstico por imagen , Calcinosis/patología , Carcinoma in Situ/diagnóstico por imagen , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Lobular/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Humanos , Hiperplasia/diagnóstico por imagen , Hiperplasia/patología , Incidencia , Mamografía , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad , Ultrasonografía Mamaria
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