RESUMEN
Rheumatoid arthritis (RA) synovial fibroblasts hyperexpress the mesenchymal cadherin-11, which is involved also in tumor invasion/metastasis, whereas anti-cadherin-11 therapeutics prevent and reduce experimental arthritis. To test the hypothesis that cadherin-11 is aberrantly expressed in RA peripheral blood, 100 patients (15 studied serially) and 70 healthy controls were analyzed by real-time reverse transcription-PCR. Cadherin-11 mRNA transcripts were detected in 69.2% of moderately/severely active RA, versus 31.8% of remaining patients (p=0.001), versus 17.1% of controls (p<0.0001). Notably, cadherin-11 positivity correlated significantly and independently only with established (>1year) polyarthritis (>4 swollen tender joints), by multivariate logistic regression analysis including various possible clinical/laboratory factors. Rare cells of undefined nature, detected by flow cytometry following CD45(-) enrichment, strongly expressed surface cadherin-11 (estimated 10-50cells/ml of blood) in 5/6 patients with polyarticular established disease versus 1/6 patients with early RA. Studies on the potential pathogenic role of circulating cells expressing cadherin-11 in RA are warranted.
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Artritis Reumatoide/sangre , Cadherinas/metabolismo , Regulación de la Expresión Génica/inmunología , ARN Mensajero/metabolismo , Adulto , Anciano , Artritis Reumatoide/inmunología , Artritis Reumatoide/metabolismo , Cadherinas/genética , Estudios de Casos y Controles , Línea Celular , Femenino , Fibroblastos/metabolismo , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/genéticaRESUMEN
Myoepithelial carcinomas exhibit a wide spectrum of cytomorphologic features and diverse clinical outcomes. As a result of their morphologic heterogeneity, they can be confused easily with many tumours. Herein we report the morphological features of myoepithelial carcinoma in a 74-year-old female clinically presenting with a parotid mass. FNAB revealed hypercellular, three-dimensional clusters with considerable overlapping and crowding of pleomorphic neoplastic cells which consisted predominantly of spindle cells, with oval to elongated to spindle shaped nuclei showing considerable variation in size. The excised tumour was solid, with cells arranged in trabeculae, nests and cords. Tumour cells were mixed epithelioid and spindle with eosinophilic or clear cytoplasm, with eccentric nuclei and prominent nuclei. Neoplastic cells were found in blood vessels, in the skin and facial nerve. Tumour cells were immunopositive for PAS, PAS-D, S-100 protein, GFAP, P63, CK5/ CK6, CK7, and CK14. This case illustrates that cytological features in FNAB generally reflect the histology. FNAB was able to confirm the diagnosis and guide patient management.
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Biomarcadores de Tumor/metabolismo , Mioepitelioma/metabolismo , Mioepitelioma/patología , Neoplasias de la Parótida/metabolismo , Neoplasias de la Parótida/patología , Anciano , Biopsia con Aguja Fina , Femenino , Humanos , InmunohistoquímicaRESUMEN
BACKGROUND: Sox11 is a transcription factor expressed in foetal and neoplastic brain tissue, including gliomas. It has been shown to suppress the tumourigenicity of glioma stem cells in vivo, thereby being hypothesised to function as a tumour suppressor. METHODS: We investigated the expression of Sox11 in 132 diffuse astrocytomas in relation to the regulator cell marker nestin, c-Met and IDH1-R132H, which have shown to be differentially expressed among the molecular subgroups of malignant gliomas, as well as to an inducer of astrocytic differentiation, that is, signal transducer and activator of transcription (p-STAT-3), clinicopathological features and survival. RESULTS: Sox11 immunoreactivity was identified in all tumours irrespective of grade, but being correlated with p-STAT-3. Three out of seven cases showed partial Sox11 promoter methylation. In >50% of our cases neoplastic cells coexpressed Sox11 and nestin, a finding further confirmed in primary glioblastoma cell cultures. Furthermore, nestin, c-Met and IDH1-R132H expression differed among grade categories. Cluster analysis identified four groups of patients according to c-Met, nestin and IDH1-R132H expression. The c-Met/nestin high-expressor group displayed a higher Sox11 expression. Sox11 expression was an indicator of favourable prognosis in glioblastomas, which remained in multivariate analysis and validated in an independent set of 72 cases. The c-Met/nestin high-expressor group was marginally with shorter survival in univariate analysis. CONCLUSIONS: We highlight the importance of Sox11 expression as a favourable prognosticator in glioblastomas. c-Met/nestin/IDH1-R132H expression phenotypes recapitulate the molecular subgroups of malignant glioma.
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Astrocitoma/genética , Neoplasias Encefálicas/genética , Proteínas de Filamentos Intermediarios/genética , Isocitrato Deshidrogenasa/genética , Proteínas del Tejido Nervioso/genética , Proteínas Proto-Oncogénicas c-met/genética , Factores de Transcripción SOXC/genética , Adulto , Anciano , Anciano de 80 o más Años , Sustitución de Aminoácidos , Arginina/genética , Astrocitoma/diagnóstico , Astrocitoma/metabolismo , Astrocitoma/mortalidad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidad , Estudios de Cohortes , Femenino , Regulación Neoplásica de la Expresión Génica , Histidina/genética , Humanos , Proteínas de Filamentos Intermediarios/metabolismo , Isocitrato Deshidrogenasa/metabolismo , Masculino , Persona de Mediana Edad , Proteínas del Tejido Nervioso/metabolismo , Nestina , Fenotipo , Fosforilación , Pronóstico , Proteínas Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo , Factores de Transcripción SOXC/metabolismo , Factor de Transcripción STAT3/metabolismo , Análisis de Supervivencia , Células Tumorales Cultivadas , Adulto JovenRESUMEN
PURPOSE: Contradictory results have been reported concerning the role of maspin and its cellular distribution in breast cancer. The purpose of this study was to examine the subcellular localization (nuclear-cytoplasmic) of maspin in breast cancer and to compare the evaluation of maspin immunostaining via light microscopy (LM) to the estimation via computerized image analysis (CIA) system. We also examined correlations between maspin expression and several clinicopathological parameters. METHODS: The sample consisted of 48 primary invasive ductal carcinomas (IDC) of the breast. Maspin immunostaining was quantified and graded via LM by two pathologists, separately in the nuclear and cytoplasmic compartments. Total maspin expression was also estimated via CIA system. Univariate non-parametric statistics and stepwise multivariate ordinal logistic regression were performed. RESULTS: Both maspin components (nuclear and cytoplasmic) were closely associated with each other (p<0.001). Total maspin score was positively and closely associated with nuclear maspin (p<0.001) and cytoplasmic maspin (p<0.001). Total maspin , nuclear maspin and cytoplasmic maspin did not correlate significantly with either age, grade, T, N and M status, stage, micro vessel density (MVD) (CD34), ki-67, p53, estrogen receptor (ER) and HER-2 status, or with any of the 4 groups of the molecular classification. The only factor that showed a borderline inverse correlation with nuclear maspin (p=0.059) was progesterone receptors (PR) positivity. CONCLUSION: The cytoplasmic and nuclear fractions of maspin seem to be closely interwoven. Evidently, both mutually intertwined counterparts were independently reflected upon the total maspin levels measured by CIA. Future studies should ideally encompass all three approaches (nuclear, cytoplasmic, total) adopted herein.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Carcinoma Ductal de Mama/química , Interpretación de Imagen Asistida por Computador , Microscopía , Serpinas/análisis , Anciano , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/terapia , Núcleo Celular/química , Citoplasma/química , Femenino , Humanos , Inmunohistoquímica , Modelos Logísticos , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Variaciones Dependientes del Observador , Oportunidad Relativa , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: c-MYC oncogene is frequently deregulated by amplification in colon adenocarcinoma. c-MYC also activates telomerase by inducing expression of its catalytic subunit (h-TERT). Furthermore, telomerase activation plays a crucial role in tumorigenesis by sustaining cellular immortality. Our aim was to evaluate the significance of c-MYC and h-TERT co-expression in colon adenocarcinoma. METHODS: Sixty paraffin embedded primary colon adenocarcinomas were cored at 1.5 mm diameter and transferred to one microarray block. Immunohistochemistry was performed using anti-h-TERT, and c - MYC antibodies. A quantitative digitized macro was performed to evaluate their expression. RESULTS: c-MYC and h-TERT overexpression was observed in 27 (45%) and 28 (46.6%) cases, respectively. Co-over expression of those genes was observed in 17 (28.3%) cases and found to be statistically significant (p=0.001). The results also showed a strong association between c-MYC and grade of differentiation of the examined neoplasms (p=0.0217rpar;. CONCLUSION: Simultaneous c-MYC and h-TERT deregulation is a relatively frequent genetic event in colon adenocarcinoma. Because c-MYC overexpression is correlated with progressive disease - due to colon adenocarcinoma dedifferentiation - inhibition of its activity combined with h-TERT regulated expression is a new target for novel therapeutic regimens.
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Adenocarcinoma/enzimología , Biomarcadores de Tumor/análisis , Neoplasias del Colon/enzimología , Interpretación de Imagen Asistida por Computador , Inmunohistoquímica , Proteínas Proto-Oncogénicas c-myc/análisis , Telomerasa/análisis , Análisis de Matrices Tisulares/métodos , Adenocarcinoma/patología , Biopsia , Diferenciación Celular , Neoplasias del Colon/patología , Femenino , Humanos , Masculino , Adhesión en Parafina , Valor Predictivo de las Pruebas , Pronóstico , Regulación hacia ArribaRESUMEN
PURPOSE: MALT lymphoma is thought to have a genetic component. Genetic studies in the greek population are rare and genetic determinants remain to be established. The current study aimed to seek correlations between genetic polymorphisms and risk of MALT lymphoma in the Greek population. PATIENTS AND METHODS: 83 MALT lymphoma patients and 60 age-matched healthy outpatients were recruited. SNPs in TNFa, LTA and CTLA-4 genes and IL1RN-VNTR and GSTT1 and GSTTM1 null polymorphisms were genotyped using published PCR/PCR-RFLP methods, while two novel PCR-RFLP methods were developed for IL-22 rs7314777 and TCF19 rs7750641 SNPs. Part of the results was validated by DNA-sequencing. Statistical analysis was performed using SPSS and the SNPstats bioinformatic tool. RESULTS: The mean age of the patients and controls were 55.9 and 56.2 years respectively. The majority of patients (63) suffered gastric marzinal zone lymphoma (GMZL) and 71.1% were stage I at diagnosis. A statistically significant association was noted for the CTLA-4 49A/ G G variant (OR:2.56,p: 0.006) and the TCF19 rs7750641 SNP T variant (OR: 3.86, p:0.023). CONCLUSIONS: Our study confirmed a role for CTLA-4 49A/G and TCF19 rs7750641 SNPs in the Greek population. Additional studies could help confirm these associations and possibly link them to prognosis or response to treatment parameters.
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Linfoma de Células B de la Zona Marginal , Antígeno CTLA-4/genética , Predisposición Genética a la Enfermedad , Grecia/epidemiología , Humanos , Linfoma de Células B de la Zona Marginal/epidemiología , Linfoma de Células B de la Zona Marginal/genética , Linfoma de Células B de la Zona Marginal/patología , Linfoma no Hodgkin , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Neoplasias Gástricas , Factores de TranscripciónRESUMEN
OBJECTIVE: The analysis of the presence of PIK3CA and B-RAF gene mutations in relation to ERK and AKT activation in diffusely infiltrating astrocytomas, in order to determine their potential role in tumor aggressiveness. METHODS: Polymerase chain reaction-single strand confirmation polymorphism (PCR-SSCP) and sequencing analysis were used for PIK3CA and B-RAF gene mutation detection. pERK and pAKT expression were examined by immunohistochemistry. RESULTS: PIK3CA mutations were found in 2 (3%) cases of glioblastomas whereas none of these cases displayed mutations in exon 15 of B-RAF gene. Neither low grade astrocytomas nor anaplastic astrocytomas revealed any mutations in these genes. Nuclear and cytoplasmic pERK immunoreactivity was displayed in 100% and 82% of cases, respectively. pERK nuclear expression was positively correlated with pERK cytoplasmic expression (p = 0.0067). Moreover, pERK nuclear expression increased in parallel with tumor grade (II, III v/s IV, p = 0.0262). Nuclear and cytoplasmic pAKT immunoreactivity was displayed in 97% and 100% of cases, respectively. Similarly, pAKT nuclear expression was positively correlated with pAKT cytoplasmic expression (p = 0.0074). pAKT cytoplasmic expression increased with increasing tumor grade (II,III v/s IV, p = 0.0930), although the latter relationship was of marginal significance. pAKT cytoplasmic expression was also positively correlated with pERK nuclear expression (p = 0.0156). CONCLUSIONS: Our study reports the low frequency of PIK3CA and B-RAF mutations in astrocytomas, despite the presence of activated ERK and AKT proteins. Moreover, the correlation of pERK nuclear and pAKT cytoplasmic expression with tumor grade suggests the possible crucial role of the activation of these proteins in human gliomagenesis.
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Astrocitoma/genética , Neoplasias Encefálicas/genética , Sistema de Señalización de MAP Quinasas/fisiología , Mutación/genética , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Astrocitoma/metabolismo , Astrocitoma/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Fosfatidilinositol 3-Quinasa Clase I , Estudios de Cohortes , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
PURPOSE: Cutaneous T cell lymphomas (CTCL) are rare and histologically diverse lymphoproliferative neoplasms, with mycosis fungoides (MF) representing the most common disease subset. Given the emerging role of myeloid-derived suppressor cells (MDSC) as a clinically applicable biomarker in solid tumors, we sought to investigate the presence of tumor-infiltrating and circulating MDSC in early- and advanced-stage MF patients and evaluate their prognostic significance in patient overall survival. METHODS: Tumor-infiltrating MDSC were assessed immunohistochemically with Arginase-1 in 31 MF and 14 non-MF skin punch biopsies. Circulating MDSC were assessed with flow cytometry in freshly isolated PBMC from 29 MF patients. Granulocytic MDSC (G-MDSC) were defined as CD11b+CD14-CD15+ and monocytic MDSC (M-MDSC) were defined as CD11b+CD14+HLA-DRlow/-. RESULTS: MDSC infiltration occurred in approximately one-third (35.5%) of CTCL lesions, with a predilection for non-MF lesions (p < 0.05). The predominant morphology of MDSC was granulocytic. Although in MF lesions the presence of MDSC infiltrates did not correlate with clinical stage, it conferred significantly worse overall survival outcomes (p < 0.05). Circulating G-MDSC were significantly higher in MF patients compared to healthy donor controls (p < 0.0001), while M-MDSC did not show any statistically significant difference. G-MDSC were significantly higher in patients with active disease compared to patients who were in partial remission (p < 0.01). As with tumor-infiltrating MDSC, clinical stage did not correlate with circulating G-MDSC levels, while prospective overall survival analysis showed that patients with high levels of circulating G-MDSC have significantly inferior outcomes (p < 0.01). CONCLUSIONS: This study shows that G-MDSC could represent a novel and easily assessable biomarker in MF, which mirrors disease activity and can predict patient subgroups with aggressive clinical features.
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Micosis Fungoide/patología , Células Supresoras de Origen Mieloide/patología , Neoplasias Cutáneas/patología , Antígeno CD11b , Recuento de Células , Femenino , Citometría de Flujo , Granulocitos/metabolismo , Granulocitos/patología , Antígenos HLA-DR , Humanos , Inmunohistoquímica , Antígeno Lewis X , Receptores de Lipopolisacáridos , Masculino , Monocitos/metabolismo , Monocitos/patología , Células Supresoras de Origen Mieloide/metabolismo , Estadificación de Neoplasias , Pronóstico , Tasa de SupervivenciaRESUMEN
Primary melanoma of the central nervous system accounts for only 1% of the cases of melanoma, having a relatively rare frequency of being reported in the literature. We report two cases of leptomeningeal melanoma of unknown primary site diagnosed after post mortem examination. In the first case, the patient presented with resisting epilepsy, whereas in the second with persisting fever and mental slowness. Cranial CT in the first patient showed postgadolinium enhancement of the ependyma and the infundibulum, while in the second there was diffuse enhancement of the leptomeninges. Analyses of the CSF in both cases did not establish the presence of malignant cells but revealed altered CSF glucose and increased CSF protein levels. There were no extracranial abnormalities. Both patients were treated for infectious meningitis and died a few days afterwards. At autopsy, all body cavities including oral cavity and the entire integument were examined. In both cases the leptomeninges were diffusely covered with brownish material. Histological examination of the brain specimens revealed the presence of a malignant neoplasm of low differentiation. Diagnosis was established with the results of immunohistochemistry, tumor cells were positive for HMB-45 and S-100 whereas they were negative for cytokeratins, CD45 and GFAP. In conclusion, both patients, although presenting with symptoms and signs highly suggestive of meningitis, suffered from leptomeningeal melanomas of unknown primary site. Clinical, radiological and histological findings are discussed with a review of the literature.
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Melanoma/diagnóstico , Melanoma/secundario , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/secundario , Meningitis/diagnóstico , Neoplasias Primarias Desconocidas/diagnóstico , Enfermedad Aguda , Diagnóstico , Humanos , Masculino , Melanoma/complicaciones , Neoplasias Meníngeas/complicaciones , Meningitis/etiología , Persona de Mediana EdadRESUMEN
Dissemination of lymphomas in serous effusions is quite common. Cytology aims to contribute in the clinical management of haematologic patients, providing an accurate and rapid diagnosis. Ancillary techniques such as immunocytochemistry and flow cytometry are essential to classify the lymphoma entity. Comprehensive awareness of the clinical picture and previous histologic documentation are essential for a lymphomatous effusion diagnosis. We report an unusual case of monomorphic epitheliotropic intestinal T-cell lymphoma, formerly known as enteropathy associated T-cell lymphoma (EATL) type II, spreading in the pleural cavity. Cell morphology and immunohistochemistry of the pleural fluid were consistent with the histology of a jejunal tumor previously excised. Flow cytometry data were consistent, though not pathognomonic for the disease. Serous effusions with evidence of lymphoma involvement should be thoroughly examined with cytology and adjuvant techniques to provide diagnosis for proper therapeutic strategies.
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Neoplasias Intestinales/patología , Linfoma de Células T/patología , Derrame Pleural Maligno/patología , Anciano , Humanos , Yeyuno/patología , MasculinoRESUMEN
Poly (ADP-ribose) polymerase 1 (PARP-1) has a central role in the repair of DNA breaks and is a promising treatment target in malignancy. We measured PARP1 mRNA levels by a SYBR-green-based PCR in the bone marrow of 74 patients with myelodysplastic syndrome (MDS) and correlated them to their demographic, hematologic and prognostic characteristics. The median PARP1 mRNA levels were correlated to the type of MDS (2008/2016 WHO classification, P=0.005) and to the IPSS score (P=0.002). A correlation was also found with the IPSS-R score (P=0.011) and the cytogenetic risk (P=0.008). In all cases, higher PARP1 levels were correlated with a higher risk category. Moreover, we found a significant survival disadvantage for patients with high PARP1 levels (median survival of 37.4 months versus 'not reached' for low PARP1 levels, P=0.0001, and a 5-year survival rate of 29.8 versus 88.9%, respectively). PARP1 mRNA levels were found to be the stronger predictor of survival in multivariate analysis. These correlations have never been reported in the past and may render PARP1 a prognostic factor to be incorporated in the current prognostic systems for MDS, also laying the basis for clinical trials evaluating PARP1 inhibitors in higher-risk MDS.
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Síndromes Mielodisplásicos/genética , Poli(ADP-Ribosa) Polimerasa-1/genética , ARN Mensajero/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
The significance of angiogenesis in Hodgkin's lymphoma (HL) is not well defined. The aim of this study was to evaluate various morphometric characteristics of microvessels in lymph node sections of 286 patients with HL at diagnosis and investigate their relationship with clinicopathologic parameters and prognosis. Microvessel density (MVD), total vascular area (TVA) and several size- and shape-related microvascular parameters were quantitated--after anti-CD34 immunohistochemical staining--in the region of most intense vascularization, using image analysis. An increase in microvessel caliber parameters (area, perimeter, major and minor axis length) and a decrease in MVD were noted with increasing stage. An inverse relationship was recorded between MVD and the number of involved sites (NIS) and LDH. In univariate analysis, overall disease-specific survival was adversely affected by MVD and TVA, whereas inferior failure-free survival (FFS) was associated with the presence of more flattened vessel sections. Multivariate analysis disclosed that the extent of angiogenesis (MVD/TVA), age and the NIS independently affected overall survival. Accordingly, FFS was independently linked to the shape of microvessels and albumin levels or the NIS. In conclusion, our data support the view that angiogenesis in HL provides independent prognostic information, requiring the concomitant evaluation of quantitative and qualitative aspects of microvascular network.
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Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Neovascularización Patológica/mortalidad , Neovascularización Patológica/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD34/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Microcirculación , Persona de Mediana Edad , Neovascularización Patológica/metabolismo , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Introduction Angiolipoma is a histological variant of lipoma and is the most common neoplasm in the trunk and extremities of young adults. It is extremely rare in elderly people, and its size is ≤4cm. Few data are available for large angiolipomas. Case History An 86-year-old patient was admitted to our surgical department due to a large mass on his left arm, which was resected. The specimen measured 19.5 × 15 × 10.5cm. Histopathological examination revealed a benign non-infiltrating angiolipoma. This is the first report of a giant angiolipoma of the arm reported in an octogenarian patient. Conclusions Giant lipomas of the upper extremities are extremely rare. Resection is associated with cure in most patients, but regular follow-up should be considered.
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Angiolipoma/patología , Brazo , Neoplasias de los Tejidos Blandos/patología , Anciano de 80 o más Años , Angiolipoma/cirugía , Brazo/cirugía , Humanos , Masculino , Neoplasias de los Tejidos Blandos/cirugíaRESUMEN
Considering the recently stated suggestion of neovascularization being implicated in myelodysplastic syndromes (MDS) pathogenesis, we evaluated multiple morphometric microvascular characteristics in MDS, in relation to clinicopathologic factors and prognosis. Trephines from 50 newly diagnosed MDS patients were immunostained for factor VIII and compared to those from 20 controls, 10 chronic myelomonocytic leukemia (CMML) and 12 acute myeloid leukemia (AML) patients. Quantitation of microvessel density (MVD), area, total vascular area (TVA), major and minor axis length, perimeter, compactness, shape factor, Feret diameter, and the number of branching vessels was performed by image analysis. Overall, the MDS group had significantly higher MVD, TVA, minor axis and shape factor values and significantly lower compactness than the control group. AML was characterized by increased vascularity compared to MDS and CMML, as well as by the presence of flattened microvessels (lower values of shape factor). Hypercellular MDS showed higher MVD. RA/RARS displayed larger caliber vessels than RAEB, which explains the favorable prognostic effect of increased size-related parameters on progression and/or survival. Moreover, decreased compactness and MVD were independent predictors of longer progression-free survival. It is concluded that angiogenesis is involved in the conversion of normal marrow to MDS and ultimately to AML and that disease progression within MDS is accompanied by qualitative alterations of the microvascular network. Furthermore, size-related parameters affect survival, while shape-related parameters and MVD are more influential with regard to progression-free survival.
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Síndromes Mielodisplásicos/patología , Neovascularización Patológica/patología , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Factor VIII/análisis , Femenino , Humanos , Leucemia Mieloide/patología , Leucemia Mielomonocítica Crónica/patología , Masculino , Microcirculación/patología , Persona de Mediana Edad , PronósticoRESUMEN
Various morphometric characteristics of microvessels, highlighted by means of anti-CD34 immunohistochemical staining, were evaluated in the bone marrow of 52 patients with chronic myeloid leukemia (CML) in chronic phase, in relation to several clinicopathologic parameters. Twenty control bone marrows and 15 cases of CML in blastic phase were also studied. Microvessel density (MVD), total vascular area (TVA) and several size- and shape-related parameters were quantitated in the region of most intense vascularization using image analysis. Overall, the group of chronic phase CML had higher MVD and size-related parameters and more branching microvessels than controls. Blastic phase was characterized by increased numbers of microvessels with a rounder shape and smaller caliber than chronic phase. A positive correlation emerged between marrow fibrosis and MVD as well as between white blood cell counts and rounder vessel sections. No relationship existed between microvascular parameters and Hasford or Sokal prognostic scores. In univariate analysis, overall and progression-free survival were adversely affected by MVD, size-related parameters, increased platelet count, age and spleen size. Multivariate analysis indicated that microvessel area was related to progression-free survival, whereas both MVD and area were significant prognosticators of overall survival, even when Hasford or Sokal scores are introduced into the model. Our data suggest that changes in angiogenic parameters may participate in the conversion of normal marrow to CML and ultimately to blastic transformation. More importantly, MVD and microvessel caliber are significant predictors of patient survival and progression.
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Células de la Médula Ósea/patología , Médula Ósea/irrigación sanguínea , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Neovascularización Patológica/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD34/análisis , Células de la Médula Ósea/inmunología , Estudios de Casos y Controles , Aberraciones Cromosómicas , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/inmunología , Masculino , Microcirculación/patología , Persona de Mediana Edad , Neovascularización Patológica/inmunología , Pronóstico , Tasa de Supervivencia , Recuento Corporal TotalRESUMEN
We report the case of a 32-year-old female with a diagnosis of supratentorial tumour. Total removal of the tumour was achieved in a two-stage procedure. Histopathology revealed a primitive neuroectodermal tumour (PNET), an unusual and highly malignant, mainly infratentorial tumour of childhood that is uncommonly described in the supratentorial compartment of adults. We review the literature and describe the existing knowledge of these tumours.
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Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Tumores Neuroectodérmicos Primitivos/patología , Neoplasias Supratentoriales , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Tumores Neuroectodérmicos Primitivos/cirugía , Neuroglía/patología , Literatura de Revisión como AsuntoRESUMEN
We investigated the expression of proliferating cell nuclear antigen (PCNA) and the number of nucleolar organizer regions (NORs) in 82 cases of CNS tumors. PCNA is a nuclear protein maximally elevated in the S phase of the cell cycle and recognized immunohistochemically in paraffin sections by the monoclonal antibody PC-10. On the other hand, NORs are loops of DNA that carry the rRNA genes and can be demonstrated in paraffin sections using an argyrophilic method (AgNORs). The present study shows a significant correlation of PCNA index and of AgNOR number with the histological grade (PCNA: I versus II, p < 0.01; II versus III, p < 0.01; and III versus IV, p < 0.05; AgNORs: I versus II, p < 0.001; II versus III, p < 0.05; and III versus IV, p < 0.001). Higher values of PCNA index (0.01 < p < 0.05) were found in recurrent tumors. Metastatic carcinomas were characterized by high PCNA indices and AgNOR numbers, similar to grade IV tumors, whereas in CNS lymphomas the malignancy grade was reflected in PCNA indices and AgNOR numbers. A wide range of PCNA and AgNOR values has been observed within each histological type and grade, probably reflecting variations in the biological behavior, but little overlap in PCNA values was present between grades II and III. The latter finding might be of importance in distinguishing between low- and high-grade CNS tumors. The linear regression coefficient between PCNA index and AgNOR number was excellent (0.91). We suggest that PCNA and AgNORs may be successfully applied in routine material to assess the growth potential of CNS tumors. Their prognostic value, however, must be validated with clinical studies.
Asunto(s)
Antígenos de Neoplasias/análisis , Neoplasias del Sistema Nervioso Central/patología , Proteínas Nucleares/análisis , Región Organizadora del Nucléolo/patología , Neoplasias del Sistema Nervioso Central/inmunología , Neoplasias del Sistema Nervioso Central/ultraestructura , Humanos , Pronóstico , Antígeno Nuclear de Célula en ProliferaciónRESUMEN
Cyclin-dependent kinase inhibitors (CKIs) prevent cyclin-dependent kinases from phosphorylating critical substrates such as retinoblastoma gene protein (pRb), hence blocking the cascade of events leading to cell proliferation. Currently, the list of CKIs includes p21WAF1/Cip1, p27Kip1, p57Kip2 (the Cip/Kip family), p15/ INK4b, p16/INK4a, p18/INK4c, and p19/INK4d (the INK4 family). Among them, p27 plays a crucial role linking extracellular growth-regulatory signals to progression to or exit from the cell cycle. Unlike p53, p16, and Rb, mutations in Kip1 and WAF1 genes are distinctly rare in bladder cancer. We analyzed immunohistochemically the expression of p27 and other interacting G1 proteins (ie, p21, p16, pRb, p53) in 120 consecutive cases of transitional cell carcinomas (TCCs) and related it to proliferation rate, clinicopathologic parameters, and survival. p27 levels were significantly higher in low-grade (P = .001), superficial (Ta-T1) (P = .001), papillary (P < .001), and slowly proliferating TCCs (rs = -0.235, P = .05). p27 also positively correlated with p16 expression (rs = 0.212, P = .05). In univariate analysis, decreased p27 expression was associated with poor overall (P = .0109) and postrelapse (P = .0344) survival, especially if combined to increased Ki-67 expression (P = .0004 and P = .036, respectively). Furthermore, in multivariate analysis, Ki-67/p27 status had the strongest bearing on the overall survival of muscle-invasive TCCs (P = .0019). Our results indicate that low p27 expression is more common in poorly differentiated muscle-invasive TCCs and is a major player in cell cycle control in these neoplasms. More importantly, the combined Ki-67/p27 expression provides prognostic information beyond that provided by conventional parameters or other cell cycle-related proteins, concerning overall survival in muscle-invasive TCCs.
Asunto(s)
Proteínas de Ciclo Celular , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Ciclinas/fisiología , Inhibidores Enzimáticos/análisis , Proteínas Asociadas a Microtúbulos/análisis , Proteínas Supresoras de Tumor , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , División Celular , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Quinasas Ciclina-Dependientes/metabolismo , Ciclinas/análisis , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Masculino , Persona de Mediana Edad , Pronóstico , Proteína de Retinoblastoma/análisis , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/análisis , Neoplasias de la Vejiga Urinaria/químicaRESUMEN
Proliferating cell nuclear antigen (PCNA) and c-myc p62 oncoprotein are two nuclear proteins expressed in proliferating and transformed cells. They can be recognized immunohistochemically in paraffin sections by the monoclonal antibodies PC-10 and c-myc 1-9E10, respectively. On the other hand, nucleolar organizer regions (NORs) are loops of DNA that carry the r-RNA genes and can be visualized in paraffin sections as black dots (AgNORs) using a silver impregnation method. It has been suggested that the mean number of AgNORs may reflect the cellular kinetics of a tumor. We independently examined 200 cases of non-Hodgkin's lymphomas using the monoclonal antibodies PC-10 and c-myc 1-9E10, as well as the AgNOR method. Our study shows a very significant correlation between PCNA, c-myc expression, and AgNOR count on the one hand and histologic grade on the other (P < .001), although a significant overlap among the three grades exists. PC-10, c-myc 1-9E10, and AgNOR scores are all shown to be linearly related, even though significant discrepancies were observed, and the correlation is stronger between PCNA and AgNORs (PCNA v c-myc p62, r = .551; PCNA v AgNORs, r = .746; c-myc p62 v AgNORs, r = .529; P < .001). A remarkable finding is that the intermediate group of lymphomas is heterogeneous as far as the proliferative rate is concerned: diffuse large cell cleaved/non-cleaved lymphomas (category G of the Working Formulation) are characterized by a significantly higher proliferative index, as evidenced by the elevated PCNA, c-myc p62, and AgNOR scores, in comparison with the other types of intermediate-grade lymphomas (P < .001). However, the proliferative rate is lower than that of the high-grade lymphomas (PCNA, P < .05; c-myc p62, P < .001; AgNORs, P < .005). No significant difference exists between B-cell and T-cell lymphomas except for the higher expression of c-myc p62 in intermediate-grade B-cell lymphomas, obviously due to the higher proliferative rate of diffuse large cell lymphomas. Based on our findings, it appears that the combination of PCNA, c-myc p62, and AgNORs provides an accurate estimate of the proliferative rate of non-Hodgkin's lymphomas in paraffin sections. Clinical studies may show whether this information has prognostic value independent of histologic classification. In addition, our results suggest that category G (diffuse large cell) lymphomas may belong to a malignancy grade higher than the intermediate grade, a suggestion consistent with their more aggressive biologic behavior.
Asunto(s)
Linfoma no Hodgkin/metabolismo , Linfoma no Hodgkin/ultraestructura , Proteínas Nucleares/metabolismo , Región Organizadora del Nucléolo/ultraestructura , Proteínas Proto-Oncogénicas c-myc/metabolismo , Antígenos de Neoplasias/metabolismo , Histocitoquímica , Humanos , Inmunohistoquímica , Antígeno Nuclear de Célula en Proliferación , Coloración y EtiquetadoRESUMEN
We investigated the expression of proliferating cell nuclear antigen (PCNA) in paraffin sections from 20 cases of medullary thyroid carcinoma (MTC). Follow-up data were available in eleven cases. PCNA index positively correlated with the degree of cellular pleomorphism (grade) of the tumor (p < 0.01), the pathologic stage (p < 0.01) and the poor clinical outcome (p < 0.05). These findings suggest that PCNA may be of prognostic significance in MTC.