0000000000299568
AUTHOR
Pedro Roldán
Epigenetic changes underlie the aggressiveness of histologically benign meningiomas that recur
Meningiomas are the most frequent primary brain tumor. Usually, they are curable by surgery, but even after seemingly complete resection, some low-grade lesions recur. Despite recent improvements, signatures having prognostic value in grade I tumors remain poorly characterized. The frequency and delicate location of these tumors suggest that the risk of recurrence might be more accurately predicted. Herein, we show an easy way to evaluate the methylation status of meningiomas and its correlation with the prognosis of the disease. A series of 120 meningiomas, including primary tumors and recurrences, were analyzed histopathologically, and 24 tumor suppressor genes (TSGs) were studied by meth…
Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma.
Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity of GBM and to correlate it with the clinical characteristics of the patients. For that purpose, we analyzed the status of EGFR and the somatic copy number alterations (CNAs) of a set of tumor suppressor genes and oncogenes. Thus, we found GBMs with high level of EGFR amplification, low level and with no EGFR amplification. Highly amplified tumors showed histological features of…
Oligoastrocitoma con diferenciación en células en anillo de sello. Estudio morfológico, ultraestructural e inmunohistoquímico
Resumen Presentamos un caso de tumor glial mixto (oligoastrocitoma) con celulas en anillo de sello. Esta diferenciacion celular es rara en tumores gliales del sistema nervioso central. En este estudio analizamos las caracteristicas morfologicas, ultraestructurales e inmunohistoquimicas del tumor. Las celulas neoplasicas con caracteristicas morfologicas en anillo de sello mostraban expresion de GFAP, S-100 y vimentina. En la discusion consideramos el diagnostico diferencial con otros tumores primarios del sistema nervioso central, asi como con metastasis cerebrales de neoplasias con diferenciacion en celulas en anillo de sello.
Association of loss of 1p and alterations of chromosome 14 in meningioma progression
Meningiomas are usually benign tumors; however, they can recur after surgical resection and occasionally show histologic progression to a higher grade II and III malignancy. The second most frequently reported genetic abnormality after 22q loss is deletion of 1p, although alterations in 9q, 10q, and 14q are also implicated in meningioma progression. Fourteen tumors comprising six benign, four atypical, and four malignant meningiomas were examined by means of cytogenetic and fluorescence in situ hybridization analysis. All tumors showed losses in different regions of 1p, with 1p11, 1p13, 1p21, 1p22, 1p32, and 1q21 breakpoints; eight tumors also presented alterations of chromosome 14. Five of…
Meningioma: Un modelo de evolución citogenética en la iniciación y progresión tumoral
Resumen Los meningiomas son tumores del sistema nervioso central con amplia heterogeneidad morfologica. Aunque son generalmente benignos, tienen la capacidad de evolucionar a un grado histologico mayor (atipico y anaplasico) que esta relacionado con un incremento de su agresividad biologica y/o la capacidad de recidivar. Esta evolucion se caracteriza a nivel citogenetico por la monosomia total o parcial del cromosoma 22 en la etapa mas temprana, seguida de cambios cromosomicos secundarios tanto numericos como estructurales durante la progresion tumoral. En este trabajo presentamos una revision sobre 85 casos de meningiomas, 43 benignos, 28 atipicos y 14 malignos, estudiando sus caracteristi…
Histologically benign metastatic meningioma: morphological and cytogenetic study. Case report.
✓ The authors report on a 75-year-old man with histologically benign fibroblastic meningioma metastasizing to the lung, liver, spleen, and kidney. The original tumor exhibited a complex karyotype involving different structural and numerical anomalies associated with monosomy of chromosome 22. The implication of chromosome 1p36 was confirmed by fluorescence in situ hybridization in most interphase nuclei. Metastases occurred 4 months after incomplete resection with prior therapeutic embolization. The recurrent tumor in turn displayed anaplastic features and an increased Ki-67 labeling index. Genetic alterations in such morphologically benign meningiomas have been implicated in the malignant …
Primary glioblastomas with and without EGFR amplification: Relationship to genetic alterations and clinicopathological features
Glioblastomas express a notable heterogeneity in both the histological and cell patterns with glial astrocytic differentiation. Primary glioblastoma, which is the most frequent presentation (90-95%), occurs mainly in older patients and arises de novo, without any clinical or histological evidence of a less malignant precursor lesion. EGFR amplification has been identified as a genetic hallmark of primary glioblastomas and occurs in 40-60% of cases. However, there exist primary glioblastomas without EGFR amplification/overexpression. The purpose of this study was to stabilize the association between cases with and without EGFR gene amplification with clinical and genetic parameters in 45 cas…
Hipofisitis granulomatosa idiopática. Estudio morfológico e inmunohistoquímico de una observación
Resumen Los procesos inflamatorios de la glandula hipofisaria constituyen un grupo de interes por su escasa frecuencia. Con frecuencia se presentan como lesiones ocupantes de espacio y cursan con cuadros de panhipopituitarismo. Ello platea problemas de diagnostico diferencial con implicaciones terapeuticas importantes En este trabajo presentamos un caso de hipofisitis granulomatosa idiopatica, en una paciente de 55 anos con crisis diarias de cefalea y panhipopituitarismo y un aumento de tamano de la glandula hipofisaria. La morfologia destaca una lesion inflamatoria granulomatosa no necrotizante, con celulas multinu-cleadas gigantes y un infiltrado linfoplasmocitario. El estudio inmunohisto…
The activation of ERK1/2 MAP kinases in glioblastoma pathobiology and its relationship with EGFR amplification.
The ERK1/2 activated protein kinase (MAPK) pathway is a critical signaling system that mediates ligand-stimulated signals for the induction of cell proliferation, differentiation and survival, involved in malignant transformation. The purpose of this study was to determine the activation of ERK1/2 in this tumor, and to determine the relationship of ERK1/2 activation with the amplification/overexpression of EGFR as well as with 9p21 locus gene alterations, both of which are genetic factors frequently associated with glioblastoma. We used immunohistochemistry and Western blot analysis to analyze the activation of ERK1/2 in 22 patients with glioblastoma, and we studied the amplification/overex…
Identification of New Genetic Clusters in Glioblastoma Multiforme: EGFR Status and ADD3 Losses Influence Prognosis
Glioblastoma multiforme (GB) is one of the most aggressive tumors. Despite continuous efforts to improve its clinical management, there is still no strategy to avoid a rapid and fatal outcome. EGFR amplification is the most characteristic alteration of these tumors. Although effective therapy against it has not yet been found in GB, it may be central to classifying patients. We investigated somatic-copy number alterations (SCNA) by multiplex ligation-dependent probe amplification in a series of 137 GB, together with the detection of EGFRvIII and FISH analysis for EGFR amplification. Publicly available data from 604 patients were used as a validation cohort. We found statistical associations…
Melanoma primario sobre quiste epidermoide. Una rara asociación tumoral. Estudio clínico-patológico
Resumen Presentamos una observacion de un quiste epidermoide de localizacion frontal parasagital, en un paciente de 69 anos de edad con crisis comiciales de 40 anos de evolucion, ictus cerebrales. El paciente desarrollo sobre la pared del quiste una neoformacion maligna identificada morfologica e inmunohistoquimicamente con la HMb45, como un melanoma maligno. La falta de antecedentes, el estudio radiologico sistemico, conducen a considerar el diagnostico de melanoma maligno primario sobre un quiste epidermoide, siendo discutida la histogenie de esta posible asociacion.
Monosomía 1p y fosfatasa alcalina en meningiomas. Estudio clinicopatológico, histoquímico y genético en 10 tumores
Fundamento Los estudios citogeneticos en meningiomas indican que la monosomia 1p es unimportante factor en su progresion. En este cromosoma, en 1p34-p36.1, aparecen localizadoslos genes que codifican la fosfatasa alcalina inespecifica (FA-in), enzima de amplia distribucionen el organismo, que se localiza tambien en los meningiomas. La perdida de expresion deesta enzima en los meningiomas ha sido asociada con la monosomia 1p en estas neoplasias. Pacientes y metodo En este trabajo estudiamos 10 meningiomas correspondientes a 8 pacientesque tienen como caracteristica comun la monosomia 1p, tres de ellos con patron morfologicobenigno, dos atipicos y 5 malignos. Se realiza un estudio citogenetic…
Cytogenetic analysis and metabolic profiling reveal a subgroup of benign meningiomas with chromosomal instabilities and aggressive metabolism
Meningiomas add up to 30% of Central Nervous System (CNS) tumours. Atypical meningiomas show a high index of recurrence 5 years after complete resection. Sometimes, meningiomas with histological diagnosis of benign meningioma show genetics characteristics of atypical meningioma. Aberrations of chromosomes 1, 14, and 22 are the most frequently reported abnormalities in meningiomas. In this communication we used cytogenetic, FISH, and NMR metabolic profiling for a molecular characterization of a series of 46 meningiomas. Tumor samples were obtained from 46 patients with meningioma (36 benign and 12 atypical) from the Clinic Hospital of Valencia. Cytogenetic analyses were performed by short-te…