Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 71
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Future Oncol ; : 1-19, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38861289

RESUMEN

Introduction: The Meet-URO 18 study is a multicentric study of patients with metastatic renal cell carcinoma receiving nivolumab in the second-line and beyond, categorized as responders (progression-free survival ≥ 12 months) and non-responders (progression-free survival < 3 months). Areas covered: The current study includes extensive immunohistochemical analysis of T-lineage markers (CD3, CD4, CD8, CD8/CD4 ratio), macrophages (CD68), ph-mTOR, CD15 and CD56 expression on tumor cells, and PD-L1 expression, on an increased sample size including 161 tumor samples (113 patients) compared with preliminary presented data. Responders' tumor tissue (n = 90; 55.9%) was associated with lower CD4 expression (p = 0.014), higher CD56 expression (p = 0.046) and higher CD8/CD4 ratio (p = 0.030). Expert opinion/commentary: The present work suggests the regulatory role of a subpopulation of T cells on antitumor response and identifies CD56 as a putative biomarker of immunotherapy efficacy.

2.
Future Oncol ; : 1-19, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38682738

RESUMEN

Introduction: The Meet-URO 18 study is a multicentric study of patients with metastatic renal cell carcinoma receiving nivolumab in the second-line and beyond, categorized as responders (progression-free survival ≥ 12 months) and non-responders (progression-free survival < 3 months). Areas covered: The current study includes extensive immunohistochemical analysis of T-lineage markers (CD3, CD4, CD8, CD8/CD4 ratio), macrophages (CD68), ph-mTOR, CD15 and CD56 expression on tumor cells, and PD-L1 expression, on an increased sample size including 161 tumor samples (113 patients) compared with preliminary presented data. Responders' tumor tissue (n = 90; 55.9%) was associated with lower CD4 expression (p = 0.014), higher CD56 expression (p = 0.046) and higher CD8/CD4 ratio (p = 0.030). Expert opinion/commentary: The present work suggests the regulatory role of a subpopulation of T cells on antitumor response and identifies CD56 as a putative biomarker of immunotherapy efficacy.


[Box: see text].

3.
BMC Endocr Disord ; 24(1): 103, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977992

RESUMEN

BACKGROUND: Congenital adrenal hyperplasia (CAH) encompassed a bunch of autosomal recessive disorders characterized by impaired cortisol levels due to an enzymatic deficiency in steroid synthesis. In adult male patients with CAH, a frequent complication related to poor disease control is the development of ectopic adrenocortical tissue in the testes, named testicular adrenal rest tumors (TART). Conversely, ovarian adrenal rest tumors (OART) in females are extremely rare and adrenal rests in sites other than gonads are so uncommon to have been described only few times in literature. CASE PRESENTATION: We report a case of a male patient with untreated CAH and oncologic history of pleomorphic sarcoma who presented with massive bilateral adrenal enlargement and adrenal rest tumors in peri-lumbar and peri-cecal sites, which mimicked metastasis from sarcoma. CONCLUSIONS: The development of massive adrenal enlargement and ectopic adrenal rest tumors in sites other than gonads, even if very uncommon, should be suspected in patients with CAH and prolonged periods of undertreatment.


Asunto(s)
Hiperplasia Suprarrenal Congénita , Tumor de Resto Suprarrenal , Humanos , Hiperplasia Suprarrenal Congénita/complicaciones , Hiperplasia Suprarrenal Congénita/patología , Hiperplasia Suprarrenal Congénita/diagnóstico , Masculino , Tumor de Resto Suprarrenal/patología , Tumor de Resto Suprarrenal/diagnóstico , Tumor de Resto Suprarrenal/etiología , Diagnóstico Diferencial , Sarcoma/diagnóstico , Sarcoma/patología , Adulto , Neoplasias de las Glándulas Suprarrenales/patología , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/secundario , Pronóstico
4.
Int J Mol Sci ; 25(2)2024 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-38255827

RESUMEN

Aldosterone (Aldo) exerts its action through binding with the mineralocorticoid receptor (MR). Clinically, a link between primary aldosteronism (PA) and thyroid diseases has been hypothesised. However, the presence and activity of MR on the thyroid have not yet been demonstrated. We investigated the gene/protein expression and activation of MR in primary thyroid cell cultures (normal rat thyroid [FRTL-5] and human papillary thyroid cancer [PTC] cell lines, BCPAP and K1) through qRT-PCR analysis, immunofluorescence, and confocal microscopy. We also studied the effects of Aldo on thyroid-specific and inflammation genes in vitro. Paired human normal and neoplastic thyroid tissues were also studied. We demonstrated both gene and protein expression and activation of MR in normal rat thyroid and human PTC lines. Incubation with Aldo induced an acute increase in IL-6 expression in both the FRTL-5 and BCPAP lines, which was antagonised by spironolactone, and an acute and late upregulation of thyroid-specific genes in FRTL-5. MR was also expressed at both gene and protein levels in normal human thyroid tissues and in PTC, with a progressive decline during neoplastic tumourigenesis, particularly in more aggressive histotypes. We present the first evidence of MR gene and protein expression in both normal and pathological thyroid cells and tissues. We have shown that MR is present and functionally activated in thyroid tissue. Binding of Aldo to MR induces the expression of inflammatory and thyroid-specific genes, and the thyroid may thus be considered a novel mineralocorticoid target tissue.


Asunto(s)
Receptores de Mineralocorticoides , Neoplasias de la Tiroides , Animales , Humanos , Ratas , Aldosterona/farmacología , Técnicas de Cultivo de Célula , Mineralocorticoides , Receptores de Mineralocorticoides/genética , Cáncer Papilar Tiroideo
5.
Dig Dis ; 41(1): 34-48, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35816999

RESUMEN

BACKGROUND: Despite the important advances in research on neuroendocrine neoplasms of the gastro-entero-pancreatic tract, their precursor lesions are much less well known. SUMMARY: This review analyzes the preneoplastic neuroendocrine lesions of the gastro-entero-pancreatic tract, by adopting a coherent anatomical benchmark. In particular, the settings in which neuroendocrine precursor lesions represent well-recognized pathophysiological and morphological entities (with eventual molecular correlates) have been distinguished from the ones in which the nature of preneoplastic changes is still obscure. KEY MESSAGES: The aim of the paper was to summarize what is known about precursor lesions of gastro-entero-pancreatic neuroendocrine tumors, with the goal of providing a useful tool for future research aimed at obtaining a fuller understanding of the underlying biology and early development of these diseases.


Asunto(s)
Neoplasias Intestinales , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Neoplasias Pancreáticas/patología , Tumores Neuroendocrinos/patología , Páncreas/patología , Neoplasias Gástricas/patología , Neoplasias Intestinales/patología
6.
Int J Mol Sci ; 23(21)2022 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-36361854

RESUMEN

We investigated the effects of bactericidal/permeability-increasing protein (BPI) alone or in combination with hyaluronic acid (HA) in two animal models: collagen-induced arthritis (CIA) and crystal-induced inflammation. In CIA, mice were intraperitoneally injected with PBS, HA, or BPI plus or minus HA, twice a week for 2 months, and then euthanized to collect paw and blood. Arthritis was assessed in ankle joints by clinical and histological evaluation. Pathogenic crystals were intraperitoneally injected in mice plus or minus BPI, or with a composition of BPI and HA. After sacrifice, total and differential leukocyte counts were determined. Cytokine levels were measured in serum and peritoneal fluids. In CIA mice, BPI improved clinical and histological outcomes (histological scores ≥2-fold), and downregulated inflammatory mediators (47-93%). In crystal-induced inflammation, BPI reduced leukocyte infiltration (total count: ≥60%; polymorphonuclear cells: ≥36%) and inhibited cytokine production (35-74%). In both models, when mice were co-treated with BPI and HA, the improvement of all parameters was greater than that observed after administration of the two substances alone. Results show that BPI attenuates CIA and inflammation in mice, and this effect is enhanced by HA co-administration. Combined use of BPI and HA represents an interesting perspective for new potential treatments in arthritis.


Asunto(s)
Artritis Experimental , Ratones , Animales , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Mediadores de Inflamación/metabolismo , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/patología , Ácido Hialurónico/metabolismo , Permeabilidad
7.
Int J Mol Sci ; 23(23)2022 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-36499693

RESUMEN

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignant tumor with neuroendocrine differentiation, with a rapidly growing incidence rate, high risk of recurrence, and aggressive behavior. The available therapeutic options for advanced disease are limited and there is a pressing need for new treatments. Tumors harboring fusions involving one of the neurotrophin receptor tyrosine kinase (NTRK) genes are now actionable with targeted inhibitors. NTRK-fused genes have been identified in neuroendocrine tumors of other sites; thus, a series of 76 MCCs were firstly analyzed with pan-TRK immunohistochemistry and the positive ones with real-time RT-PCR, RNA-based NGS, and FISH to detect the eventual underlying gene fusion. Despite 34 MCCs showing pan-TRK expression, NTRK fusions were not found in any cases. As in other tumors with neural differentiation, TRK expression seems to be physiological and not caused by gene fusions.


Asunto(s)
Carcinoma de Células de Merkel , Neoplasias , Neoplasias Cutáneas , Humanos , Receptor trkA/genética , Carcinoma de Células de Merkel/genética , Factores de Crecimiento Nervioso/uso terapéutico , Receptor trkC/genética , Neoplasias/patología , Neoplasias Cutáneas/genética , Proteínas de Fusión Oncogénica/genética , Biomarcadores de Tumor/genética
8.
Int J Mol Sci ; 22(7)2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33807389

RESUMEN

MicroRNAs (miRNAs) are small non-coding RNAs that play a pivotal role in many aspects of cell biology, including cancer development. Within esophageal cancer, miRNAs have been proved to be involved in all phases of carcinogenesis, from initiation to metastatic spread. Several miRNAs have been found to be dysregulated in esophageal premalignant lesions, namely Barrett's esophagus, Barrett's dysplasia, and squamous dysplasia. Furthermore, numerous studies have investigated the alteration in the expression levels of many oncomiRNAs and tumor suppressor miRNAs in esophageal squamous cell carcinoma and esophageal adenocarcinoma, thus proving how miRNAs are able modulate crucial regulatory pathways of cancer development. Considering these findings, miRNAs may have a role not only as a diagnostic and prognostic tool, but also as predictive biomarker of response to anti-cancer therapies and as potential therapeutic targets. This review aims to summarize several studies on the matter, focusing on the possible diagnostic-therapeutic implications.


Asunto(s)
Neoplasias Esofágicas/genética , MicroARNs/genética , MicroARNs/uso terapéutico , Adenocarcinoma , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Progresión de la Enfermedad , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Esófago/patología , Expresión Génica , Perfilación de la Expresión Génica , Humanos , MicroARNs/metabolismo , Lesiones Precancerosas/genética , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , Pronóstico
9.
Int J Mol Sci ; 22(18)2021 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-34576114

RESUMEN

Gastric carcinoma (GC) represents one of the most common and most lethal malignancies worldwide. The histopathological characterization of GC precursor lesions has provided great knowledge about gastric carcinogenesis, with the consequent introduction of effective strategies of primary and secondary prevention. In recent years, a large amount of data about the molecular events in GC development is emerging, flanking the histomorphological descriptions. In this review, we describe the landscape of molecular alterations in gastric pre-invasive lesions with a glance at their potential use in the diagnostic and therapeutic decision-making process.


Asunto(s)
Lesiones Precancerosas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Humanos , Terapia Molecular Dirigida , Invasividad Neoplásica , Factores de Riesgo , Neoplasias Gástricas/clasificación , Neoplasias Gástricas/epidemiología
10.
Int J Mol Sci ; 22(8)2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33917086

RESUMEN

Acral melanoma (AM) is a rare and aggressive subtype of melanoma affecting the palms, soles, and nail apparatus with similar incidence among different ethnicities. AM is unrelated to ultraviolet radiation and has a low mutation burden but frequent chromosomal rearrangements and gene amplifications. Next generation sequencing of 33 genes and somatic copy number variation (CNV) analysis with genome-wide single nucleotide polymorphism arrays were performed in order to molecularly characterize 48 primary AMs of Italian patients in association with clinicopathological and prognostic features. BRAF was the most commonly mutated gene, followed by NRAS and TP53, whereas TERT promoter, KIT, and ARID1A were less frequently mutated. Gains and losses were recurrently found in the 1q, 6p, 7, 8q, 20 and 22 chromosomes involving PREX2, RAC1, KMT2C, BRAF, CCND1, TERT, and AKT3 genes, and in the 6q, 9, 10, 11q and 16q chromosomes including CDKN2A, PTEN, and ADAMTS18 genes, respectively. This study confirmed the variety of gene mutations and the high load of CNV in primary AM. Some genomic alterations were associated with histologic prognostic features. BRAF mutations, found with a higher rate than previously reported, correlated with a low Breslow thickness, low mitotic count, low CNV of the AMs, and with early-stage of disease.


Asunto(s)
Biomarcadores de Tumor , Susceptibilidad a Enfermedades , Melanoma/etiología , Neoplasias Cutáneas/etiología , Anciano , Anciano de 80 o más Años , Variaciones en el Número de Copia de ADN , Femenino , Humanos , Italia , Masculino , Melanoma/diagnóstico , Melanoma/mortalidad , Persona de Mediana Edad , Mutación , Clasificación del Tumor , Estadificación de Neoplasias , Polimorfismo de Nucleótido Simple , Pronóstico , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/mortalidad , Melanoma Cutáneo Maligno
11.
Pathologica ; 113(3): 218-229, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34294939

RESUMEN

The 2019 WHO classification of digestive system tumors significantly reformed the classificatory definition of serrated lesions of the colorectal mucosa and added new essential diagnostic criteria for both conventional adenomas and hereditary gastrointestinal polyposis syndromes. Histopathological examination of colorectal adenocarcinoma precursors lesions represents an important segment of daily clinical practice in a pathology department and is essential for the implementation of current colorectal adenocarcinoma secondary prevention strategies. This overview will focus on a schematic histopathological and molecular classification of precursor lesions arising within colorectal mucosa.


Asunto(s)
Adenocarcinoma , Adenoma , Pólipos del Colon , Neoplasias Colorrectales , Adenocarcinoma/genética , Adenoma/genética , Pólipos del Colon/genética , Neoplasias Colorrectales/genética , Humanos , Mutación
12.
Endocr J ; 67(9): 929-934, 2020 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-32475862

RESUMEN

Autoimmune Addison's disease (AAD) is a rare condition occurring either in isolation or associated with other autoimmune diseases as part of an autoimmune polyglandular syndrome (APS) type 1, 2 or 4. Multiple endocrine neoplasia (MEN) type 1, 2 or 4 is a hereditary autosomal dominant cancer syndrome. Medullary thyroid carcinoma and pheochromocytoma are neoplasms common to MEN-2a and MEN-2b. We describe a unique, complex case of a man resulted affected by both APS-2 and MEN-2a. The patient developed Hashimoto's thyroiditis, diabetes mellitus type 1 and AAD, despite testing negative for adrenal cortex autoantibodies (ACA) and steroid 21-hydroxylase autoantibodies (21-OHAb). Moreover, he had also a family history for MEN-2a and he first developed medullay thyroid cancer, then bilateral pheochromocytoma on the adrenal substrate of an AAD. On adrenal histology we found complete bilateral cortical atrophy in the presence of a lymphocytic infiltration and fibrosis, confirming an ACA and 21-OHAb-negative AAD. This datum is the first documented in a living individual and confirms that the absence of autoantibodies is not incompatible with an autoimmune disease and confirms that AAD is a cell-mediated autoimmune disease limited to the adrenal cortex and sparing medullary. In the light of a literature review concerning the association between APS and MEN, this is the first proven case to be reported in humans. Finally, our findings suggest that adrenal medullary tumor can develop even on an adrenal gland with cortical atrophy due to autoimmune adrenalitis.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasia Endocrina Múltiple/complicaciones , Feocromocitoma/complicaciones , Poliendocrinopatías Autoinmunes/complicaciones , Neoplasias de las Glándulas Suprarrenales/inmunología , Adulto , Humanos , Masculino , Neoplasia Endocrina Múltiple/inmunología , Linaje , Feocromocitoma/inmunología , Poliendocrinopatías Autoinmunes/inmunología
13.
Pathologica ; 112(3): 153-165, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33179619

RESUMEN

Gastric biopsies represent one of the most frequent specimens that the pathologist faces in routine activity. In the last decade or so, the landscape of gastric pathology has been changing with a significant and constant decline of H. pylori-related pathologies in Western countries coupled with the expansion of iatrogenic lesions due to the use of next-generation drugs in the oncological setting. This overview will focus on the description of the elementary lesions observed in gastric biopsies and on the most recent published recommendations, guidelines and expert opinions.


Asunto(s)
Gastritis , Biopsia , Endoscopía , Mucosa Gástrica/patología , Gastritis/etiología , Gastritis/patología , Helicobacter pylori/patogenicidad , Humanos , Clasificación del Tumor , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Factores de Riesgo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etiología , Neoplasias Gástricas/patología
14.
J Hepatol ; 71(1): 130-142, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30878582

RESUMEN

BACKGROUND & AIMS: In vitro, cell function can be potently regulated by the mechanical properties of cells and of their microenvironment. Cells measure these features by developing forces via their actomyosin cytoskeleton, and respond accordingly by regulating intracellular pathways, including the transcriptional coactivators YAP/TAZ. Whether mechanical cues are relevant for in vivo regulation of adult organ homeostasis, and whether this occurs through YAP/TAZ, remains largely unaddressed. METHODS: We developed Capzb conditional knockout mice and obtained primary fibroblasts to characterize the role of CAPZ in vitro. In vivo functional analyses were carried out by inducing Capzb inactivation in adult hepatocytes, manipulating YAP/Hippo activity by hydrodynamic tail vein injections, and treating mice with the ROCK inhibitor, fasudil. RESULTS: We found that the F-actin capping protein CAPZ restrains actomyosin contractility: Capzb inactivation alters stress fiber and focal adhesion dynamics leading to enhanced myosin activity, increased traction forces, and increased liver stiffness. In vitro, this rescues YAP from inhibition by a small cellular geometry; in vivo, it induces YAP activation in parallel to the Hippo pathway, causing extensive hepatocyte proliferation and leading to striking organ overgrowth. Moreover, Capzb is required for the maintenance of the differentiated hepatocyte state, for metabolic zonation, and for gluconeogenesis. In keeping with changes in tissue mechanics, inhibition of the contractility regulator ROCK, or deletion of the Yap1 mechanotransducer, reverse the phenotypes emerging in Capzb-null livers. CONCLUSIONS: These results indicate a previously unsuspected role for CAPZ in tuning the mechanical properties of cells and tissues, which is required in hepatocytes for the maintenance of the differentiated state and to regulate organ size. More generally, it indicates for the first time that mechanotransduction has a physiological role in maintaining liver homeostasis in mammals. LAY SUMMARY: The mechanical properties of cells and tissues (i.e. whether they are soft or stiff) are thought to be important regulators of cell behavior. Herein, we found that inactivation of the protein CAPZ alters the mechanical properties of cells and liver tissues, leading to YAP hyperactivation. In turn, this profoundly alters liver physiology, causing organ overgrowth, defects in liver cell differentiation and metabolism. These results reveal a previously uncharacterized role for mechanical signals in the maintenance of adult liver homeostasis.


Asunto(s)
Actinas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteína CapZ/metabolismo , Proteínas de Ciclo Celular/metabolismo , Hepatocitos/fisiología , Hígado , Mecanotransducción Celular/fisiología , Proteínas Serina-Treonina Quinasas/metabolismo , Animales , Células Cultivadas , Elasticidad , Vía de Señalización Hippo , Humanos , Péptidos y Proteínas de Señalización Intracelular/fisiología , Hígado/crecimiento & desarrollo , Hígado/metabolismo , Hígado/fisiopatología , Ratones , Ratones Noqueados , Transducción de Señal , Proteínas Señalizadoras YAP
15.
Cancer Cell Int ; 19: 209, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31406485

RESUMEN

The recent advent of immunomodulatory therapies into the clinic has demanded the identification of innovative predictive biomarkers to identify patients most likely to respond to immunotherapy and support the design of tailored clinical trials. Current molecular testing for selection of patients with gastrointestinal or pulmonary carcinomas relies on the prevalence of PD-L1 expression in tumor as well as immune cells by immunohistochemistry and/or on the evaluation of the microsatellite status. Tumor Mutational Burden (TMB) has emerged as a promising novel biomarker in this setting to further aid in patient selection. This has been facilitated by the increasing implementation of molecular pathology laboratories with comprehensive next generation sequencing (NGS) technologies. However, the significant overall costs and expertise required for the interpretation of NGS data has limited TMB evaluation in routine diagnostics, so far. This review focuses on the current use of TMB analysis in the clinical setting in the context of immune checkpoint inhibitor therapies.

16.
Histopathology ; 71(5): 769-777, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28628241

RESUMEN

AIMS: Mantle cell lymphoma (MCL) is characterized by distinctive histological and molecular features. Aberrant expression of BCL6 and CD10 has been reported occasionally, but the biological features of such cases are largely unknown. This study aimed to define the epidemiological, histological and cytogenetic characteristics of BCL6 and CD10-positive MCLs, also investigating possible biological features. METHODS AND RESULTS: A total of 165 cases of cyclin D1 and t(11;14)(q13;q34)-positive MCLs were studied for CD10 and BCL6 immunohistochemical expression, which was documented in 26 of 165 (15.8%) cases (BCL6 17 of 165; CD10 11 of 165; BCL6 and CD10 co-expression two of 165). CD10-positivity was significantly more frequent in females (63.3%; P < 0.01). Either expression correlated significantly with higher mean proliferation index and higher prevalence of MUM1 positivity (P < 0.05). Fluorescence in-situ hybridization (FISH) for BCL6 (3q27) gene derangements was performed on the BCL6- and CD10-positive cases and 98 matched controls: amplifications were documented more frequently in BCL6-positive than -negative cases (50.0% versus 19.4% of cases) (P < 0.05). The mutational status of the variable immunoglobulin heavy chain genes (IGVH) was investigated by Sanger sequencing: five of the six successfully tested cases (83.3%) showed no somatic hypermutations. CONCLUSIONS: Aberrant CD10 and BCL6 expression defines a subset of MCLs with higher mean Ki-67 index and higher prevalence of MUM1 expression. BCL6 protein positivity correlates with cytogenetic aberrations involving the BCL6 gene. Although examined successfully in few cases, the high prevalence of unmutated IGVH genes also points at a pregerminal cell origin for these phenotypically aberrant cases.


Asunto(s)
Biomarcadores de Tumor/análisis , Linfoma de Células del Manto/patología , Neprilisina/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-6/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/metabolismo , Masculino , Persona de Mediana Edad , Adulto Joven
17.
Histopathology ; 71(3): 470-474, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28502094

RESUMEN

AIMS: PD-1/PD-L1 checkpoint immunotherapy has been proposed recently as a promising treatment in relapsed/refractory disease, used eventually in combination with traditional chemotherapy in different cancer settings. To date, no data are available concerning PD-L1 expression in ampulla of Vater carcinoma and its pre-invasive lesions. METHODS AND RESULTS: We assessed the immunohistochemical expression of PD-L1 in a series of 26 ampullary adenocarcinomas, 50 ampullary dysplastic lesions and 10 normal duodenal mucosa samples. Moreover, in all cases DNA mismatch repair proteins status was investigated. PD-L1 was expressed in seven of 26 (26.9%) invasive carcinomas and three of 50 (6.0%) dysplastic samples. Most of the PD-L1-positive tumours (seven of 10) were intestinal-type and poorly differentiated (G3). The number of PD-L1-positive stromal lymphoid cells was significantly higher in dysplastic and invasive lesions than in the normal samples (P = 0.011). Nineteen dysplastic lesions and eight invasive carcinomas did not show any evident epithelial or stromal PD-L1 expression. Four of the carcinomas were mismatch repair-deficient and two of these were PD-L1-positive. Furthermore, mismatch repair-deficient lesions showed a significantly higher average of PD-L1-positive stromal lymphoid cells than those of neoplastic PD-L1-negative samples (62.8 versus 21.6; P < 0.001). CONCLUSIONS: The present results suggest a role of the PD-1/PD-L1 axis in ampullary adenocarcinomas, and therefore this may also prompt consideration of checkpoint immunotherapy as a novel promising treatment for these tumours.


Asunto(s)
Adenocarcinoma/patología , Ampolla Hepatopancreática/patología , Antígeno B7-H1/biosíntesis , Biomarcadores de Tumor/análisis , Adenocarcinoma/inmunología , Adulto , Anciano , Ampolla Hepatopancreática/inmunología , Antígeno B7-H1/análisis , Biomarcadores de Tumor/inmunología , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/patología , Neoplasias del Conducto Colédoco/inmunología , Neoplasias del Conducto Colédoco/patología , Neoplasias Duodenales/inmunología , Neoplasias Duodenales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/inmunología , Lesiones Precancerosas/patología
18.
Clin Chem Lab Med ; 54(9): 1531-9, 2016 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-26863344

RESUMEN

BACKGROUND: Risk stratification in patients with papillary thyroid carcinoma (PTC) currently relies on postoperative parameters. Testing for BRAF mutations preoperatively may serve as a novel tool for identifying PTC patients at risk of persistence/recurrence after surgery. METHODS: The study involved 185 consecutive patients with a histological diagnosis of PTC and BRAF analysis performed on thyroid fine-needle aspiration biopsy (FNAB). We assessed BRAF status in FNAB specimens obtained before thyroidectomy for PTC, and examined its association with the clinicopathological characteristics identified postoperatively, and with outcome after a mean 55±15 months of follow-up. RESULTS: One hundred and fifteen of 185 (62%) PTCs carried a BRAF mutation. Univariate analysis showed that BRAF status correlated with the histological variant of PTC, cancer size, and stage at diagnosis, but not with gender, age, multifocality, or lymph node involvement. BRAF-mutated cases had a higher prevalence of persistent/recurrent disease by the end of the follow-up (11% vs. 8%), but this difference was not statistically significant. The Kaplan-Meier curve shows that among the patients with persistent/recurrent disease, BRAF-mutated patients needed a second treatment earlier than patients with BRAF wild-type, although the difference did not completely reach the statistical significance. CONCLUSIONS: Our study confirmed that preoperatively-identified BRAF mutation are associated with certain pathological features of PTC that correlate with prognosis. We speculate that it has a role in identifying PTCs that would generally be considered low-risk but that may reveal an aggressive behavior during their follow-up.


Asunto(s)
Carcinoma/diagnóstico , Carcinoma/genética , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/genética , Tiroidectomía , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Fina , Carcinoma/patología , Carcinoma/cirugía , Carcinoma Papilar , Análisis Mutacional de ADN , ADN de Neoplasias/análisis , ADN de Neoplasias/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Adulto Joven
19.
Thyroid ; 34(2): 177-185, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38047536

RESUMEN

Background: The International Medullary Thyroid Carcinoma Grading System (IMTCGS) divides medullary thyroid carcinoma (MTC) into two categories, high- and low-grade tumors, which has a profound impact on patient outcomes. The aim of this study was to explore the association between IMTCGS grading, clinical data, and molecular status in sporadic MTC. Methods: A retrospective cohort study was performed on consecutive sporadic MTCs from patients undergoing initial surgery between January 2000 and January 2022 at the Padua Endocrine Surgery Unit. Clinical, pathological, and follow-up data were collected, tumors were graded, and somatic mutations of RET and RAS genes were analyzed. Patient outcomes were based on Ct levels and MTC-related deaths. Survival analyses were carried out employing the Kaplan-Meier method and the log-rank test. A Cox proportional hazard regression model was employed for multivariable survival analysis with the following covariates: somatic RET mutation, MTC stage at diagnosis, sex, age at diagnosis, and IMTCGS grade. Results: We included 141 consecutive sporadic MTCs. The median follow-up was 80.0 months (interquartile ranges: 41.5-122.5 months). Seventeen patients (12.1%) died from disease-related causes. 107/141 (76.9%) were classified as low-grade tumors, 32/141 (23.1%) as high-grade. Patients carrying a RET mutation had more aggressive features and shorter disease-specific survival (DSS) (p = 0.001) and were more frequently classified high-grade than low-grade MTC (p < 0.001). At multivariable survival analysis, only IMTCGS grading was independently associated with DSS (hazard ratio 8.8 [confidence interval: 2.7-28.3], p = 0.005). RET mutations, in particular RET-M918T, were more frequent in high-grade than in low-grade MTC (68.8% vs. 29.4% mutated in RET, 46.9% vs. 12.7% mutated in RET-M918T; p < 0.001). None of the high-grade tumors was mutated in the RAS gene, but the mutation was present in 11.8% of low-grade tumors. Conclusions: IMTCGS grading was associated with DSS independently of other clinical, pathological, and molecular factors. Moreover, MTC grading was associated with RET and RAS patterns, which explains, at least in part, the molecular basis of the aggressive behavior of high-grade MTC.


Asunto(s)
Carcinoma Medular , Carcinoma Neuroendocrino , Neoplasias de la Tiroides , Humanos , Carcinoma Medular/genética , Estudios Retrospectivos , Proteínas Proto-Oncogénicas c-ret/genética , Carcinoma Neuroendocrino/genética , Neoplasias de la Tiroides/genética
20.
Artículo en Inglés | MEDLINE | ID: mdl-38888173

RESUMEN

CONTEXT: The search for somatic mutations in adrenals resected from primary aldosteronism (PA) patients is being performed by Sanger sequencing, often implemented with immunohistochemistry (IHC)-guidance focused on aldosterone-producing (CYP11B2-positive) areas. OBJECTIVE: To investigate the impact of double IHC for CYP11B1 and CYP11B2 on Sanger and next generation sequencing (NGS). METHODS: We investigated 127 consecutive adrenal aldosterone producing adenoma from consenting surgically cured PA patients using double IHC for CYP11B1 and CYP11B2, Sanger sequencing and NGS. RESULTS: Double IHC for CYP11B2 and CYP11B1 revealed 3 distinct patterns: CYP11B2-positive adenoma (pattern 1), mixed CYP11B1/CYP11B2-positive adenoma (pattern 2), and adrenals with multiple small CYP11B2-positive nodules (pattern 3). Sanger sequencing allowed detection of KCNJ5 mutations in 44% of the adrenals; NGS revealed such mutations in 10% of those negative at Sanger and additional mutations in 61% of the cases. Importantly the rate of KCNJ5 mutations differed across patterns: 17.8% in pattern 1, 71.4% in pattern 2, and 10.7% in pattern 3 (χ2=22.492, p<0.001). CONCLUSIONS: NGS allowed detection of mutations in many adrenals that tested negative at Sanger sequencing. Moreover, the different distribution of KCNJ5 mutations across IHC patterns indicates that IHC-guided sequencing protocols selecting CYP11B2-positive areas could furnish results that might not be representative of the entire mutational status of the excised adrenal, which is important at a time when KCNJ5 mutations are suggested to drive management of APA patient.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA