RESUMEN
Using the example of a recurrent tumor with a 10-year follow-up, the authors show that mutation of the IDH1/2 genes in astrocytomas is not always an early event in the pathogenesis of glioma, that in rare cases a 1p19q codeletion can be found in astrocytomas, and that IDH-mutant tumors can occur in childhood.
Asunto(s)
Astrocitoma , Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Glioma/genética , Astrocitoma/genética , Mutación , Isocitrato Deshidrogenasa/genéticaRESUMEN
The paper describes a clinical case of atypical teratoid/rhabdoid tumor with preserved INI1 expression and SMARCA4 gene mutations in an 8-month-old girl. Genome-wide DNA methylation, hierarchical clustering, and next-generation sequencing were used to make a tumor diagnosis. However, BRG1 immunohistochemical examination may be recommended in the routine practice of diagnosis and study of childhood CNS malignant tumors.
Asunto(s)
Neoplasias del Sistema Nervioso Central , Tumor Rabdoide , Proteína SMARCB1 , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/genética , Niño , Proteínas Cromosómicas no Histona , ADN Helicasas/metabolismo , Femenino , Humanos , Lactante , Proteínas Nucleares/metabolismo , Tumor Rabdoide/diagnóstico , Tumor Rabdoide/genética , Proteína SMARCB1/metabolismo , Factores de Transcripción/metabolismoRESUMEN
UNLABELLED: Glioblastoma is the most common primary malignant glial tumor of the brain in adult patients. AIM: to define the prognostic value of isocitrate dehydrogenase-1 (IDH-1) mutation and methylguanine-DNA methyltransferase (MGMT) methylation status in patients with glioblastoma (GB) and to analyze the impact of clinical data (gender, age, and tumor site), histological variants of the tumor structure, and time to development of recurrences on the course of the disease. SUBJECTS AND METHODS: The investigation enrolled 63 GB patients aged 18 to 71 years who had received combined treatment (surgery, chemo- and radiotherapy) at the N.I. Burdenko Research Institute of Neurosurgery, Ministry of Health of the Russian Federation, in the period 2008 to 2011. The investigators performed a morphological examination of all tumor tissue samples and an immunohistochemical examination using anti-IDH-1 R-132 antibody clone («Dianova¼, Germany) and defined MGMT methylation status by a polymerase chain reaction using the CpGenome DNA Modification Kit («Chemicon International¼, USA). The data were statistically processed using a package of Statistica 6.0 programs. RESULTS: Patient age, time to development of recurrent glioblastoma, mutations in the IDH-1 gene and MGMT were found to be prognostic factors for overall survival among adult patients in this category. CONCLUSION: Analysis of clinical findings and identification of molecular genetic aberrations in the tumor cells will be able to elaborate an individual approach to treating patients with glioblastoma in order to increase their survival rates and to improve quality of life.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Encefálicas/diagnóstico , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Glioblastoma/diagnóstico , Isocitrato Deshidrogenasa/genética , Proteínas Supresoras de Tumor/genética , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Estudios de Casos y Controles , Metilación de ADN , Metilasas de Modificación del ADN/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Femenino , Humanos , Isocitrato Deshidrogenasa/metabolismo , Masculino , Persona de Mediana Edad , Mutación , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Glioblastomas in children and adults are a heterogeneous group of tumors that can be divided into at least three different subgroups: pediatric glioblastomas, IDH1-mutant glioblastomas in adults (the most favorable prognostic subtype), and IDH1-wild type glioblastomas in adults. According to the frequency of detected cytogenetic aberrations (amplification of the MYC/MYCN, EGFR and PDGRFA oncogenes, homozygous deletion of the CDKN2A gene, and deletion of the PTEN gene), pediatric glioblastomas bear analogy to the subgroup of IDH1-mutant glioblastomas in adults.
Asunto(s)
Aberraciones Cromosómicas , Glioblastoma/genética , Glioblastoma/patología , Proteínas de Neoplasias/genética , Adolescente , Adulto , Niño , Preescolar , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The cytogenetic profile of chromosome 17 was studied in 180 medlloblastomas by the interphasic FISH technique, which revealed the high incidence of this aberration and its association with the poor clinical course of the disease. The interphasic cytogenetic analysis of chromosome 17 abnormalities in medulloblastoma biopsy specimens may be recommended for its inclusion into a complex of laboratory diagnostic methods used in the examination of these tumors.
Asunto(s)
Neoplasias Cerebelosas/genética , Aberraciones Cromosómicas , Cromosomas Humanos Par 17/genética , Meduloblastoma/genética , Adolescente , Adulto , Neoplasias Cerebelosas/epidemiología , Neoplasias Cerebelosas/terapia , Femenino , Humanos , Hibridación Fluorescente in Situ , Estimación de Kaplan-Meier , Masculino , Meduloblastoma/epidemiología , Meduloblastoma/terapia , Valor Predictivo de las PruebasRESUMEN
Meningiomas of the sphenoid wing (SW) frequently show an invasive pattern of growth and cause destruction of the adjacent structures. As a result, the rate of recurrent SW meningiomas is as high as 30%. Cytogenetic investigations showed no aberrations specific to invasively growing meningiomas. During this study, the authors evaluated 10 invasive and 5 non-invasive SW meningiomas via comparative genome hybridization (CGH) (matrix CGH), by using the gene chips of GenoSensor Array micromatrixes. The mean number of aberrations in the tumor cells was much greater in case of invasive meningiomas (67.4 versus 40.5 in case of non-invasive SW meningiomas. Furthermore, in invasive SW meningiomas, there were frequently losses in loci 1p, 6q, and 14q and gains in loci 15q and 10, which had been predetermined as molecular markers of stepwise progression of meningioma. Thus, the presence of a complex cytogenetic profile and progression-associated chromosome aberrations in benign SW meningiomas is linked with the increase of their invasive potential. Due to the fact that there are no well-defined adjuvant therapy regimens for recurring meningiomas at present, the revealed genomic aberrations may become potential targets for searching for drugs and a therapeutic intervention in future.
Asunto(s)
Aberraciones Cromosómicas , Neoplasias Meníngeas , Meningioma , Hueso Esfenoides/patología , Adulto , Deleción Cromosómica , ADN de Neoplasias/genética , Humanos , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patología , Meningioma/genética , Meningioma/patología , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Hibridación de Ácido Nucleico , PronósticoRESUMEN
Clinical and morphological studies were undertaken to examine 168 patients with glioblastomas of the cerebral hemispheres. They revealed that the longevity of the hemispheres was substantially influenced by three immunobiological criteria: the proliferative potential defined as a labelling index (LI) of proliferative cell nuclear antigen (PCNA), the expression of intracellular domain of epidermal growth factor receptor (EGFR) and the rate of apoptosis identified by ISEL. The risk for shorter survivals increases with higher PCNA LI and with the EGFR expression in the tumor. In contrast, the rate of apoptosis is a good predictor since the risk for shorter postoperative survivals progressively reduces with high apoptotic indices. The expression of cancer proteins p53 and bc12 in the glioblastomas produces no noticeable effect on the patients survival.
Asunto(s)
Apoptosis , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Proteínas de Neoplasias/metabolismo , Adolescente , Adulto , Anciano , Biopsia , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/cirugía , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Receptores ErbB/metabolismo , Femenino , Glioblastoma/mortalidad , Glioblastoma/patología , Glioblastoma/cirugía , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Antígeno Nuclear de Célula en Proliferación/metabolismo , Modelos de Riesgos ProporcionalesRESUMEN
Tumor-associated proteins are studied immunohistochemically in 86 medulloblastomas (MB). Three main variants of their coexpression (70% of all cases studied) are distinguished. The 1st variant (24 cases): expression of Rb and nm23 proteins and the lack of tenascin expression. The 2nd variant (25 cases): tenascin expression and lack of Rb and nm23 expression. The 3rd variant (12 cases): the expression of tenascin, Rb, p53 and/or bc12. Tenascin-positive MB much more frequently expressed oncoproteins p53, bc12, c-erb B-2 and p30/32, and had higher indices of "growth fraction". Tenascin immunoreactivity and that of other oncoproteins prevailed in MB with desmoplasia and in tumors with immunohistochemical features of neuronal differentiation.
Asunto(s)
Biomarcadores de Tumor , Neoplasias Cerebelosas/metabolismo , Meduloblastoma/metabolismo , Proteínas de Unión al GTP Monoméricas , Proteínas de Neoplasias/biosíntesis , Nucleósido-Difosfato Quinasa , Adolescente , Adulto , Neoplasias Cerebelosas/patología , Niño , Preescolar , Femenino , Humanos , Masculino , Meduloblastoma/patología , Nucleósido Difosfato Quinasas NM23 , Proteína de Retinoblastoma/biosíntesis , Tenascina/biosíntesis , Factores de Transcripción/biosíntesisRESUMEN
Apoptosis was studied in 80 glioblastomas by ISEL method. Considerable variability of apoptosis index was found in glioblastomas, this indicating a non-uniform role of the "programmed death" in these malignant tumors. A certain association is established between the apoptosis expression and expression of p53 oncoprotein. The highest and more stable apoptosis indices were in glioblastomas with p53 labeling index from 11 to 35%.
Asunto(s)
Apoptosis/fisiología , Neoplasias Encefálicas/química , Glioblastoma/química , Adulto , Anciano , Neoplasias Encefálicas/patología , División Celular/fisiología , Femenino , Glioblastoma/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteína p53 Supresora de Tumor/biosíntesisRESUMEN
Neurocytoma accounts for 0.5% of all tumors of the central nervous system. 18 such tumors are described. Homogeneous expression of neuron-specific enolase and synaptophysin and heterogeneous expression of PCNA and some proteins are characteristic for these tumors. Two immunophenotypic variants are distinguished: p30-32 positive tumors with high values of PCNA; c-er B-2 HSPh-highly positive variant with lower indices of the "growth fractions".
Asunto(s)
Antígenos de Neoplasias/análisis , Neoplasias Encefálicas/inmunología , Neurocitoma/inmunología , Fosfopiruvato Hidratasa/análisis , Antígeno Nuclear de Célula en Proliferación/análisis , Adolescente , Adulto , Neoplasias Encefálicas/diagnóstico , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Inmunofenotipificación , Lactante , Masculino , Persona de Mediana Edad , Neurocitoma/diagnóstico , Sinaptofisina/análisisRESUMEN
Studying the proliferative activity of 60 astrocytic gliomas in the cerebral hemispheres by immunohistochemical detection of proliferative nuclear antigen in their nuclei has revealed that the expression of this cancer proliferative marker statistically significantly differs in the labelling index of proliferative nuclear antigen in benign and anaplastic astrocytomas (5.2 and 34.7%, respectively). Analyzing the relationships between the proliferative activity of astrocytic gliomas to their histostructural features has ascertained that there are higher proliferative nuclear antigen labelling induces in the astrocytic gliomas along with mitotic figures, proliferation of the vascular endothelium, vesicle-shaped nuclear, and multinuclear cells, the two latter signs are of greater importance as they are much more frequently encountered. The above-mentioned histological signs may be regarded as criteria for diagnosis of malignant transformation of astrocytomas.
Asunto(s)
Astrocitoma/patología , Neoplasias Encefálicas/patología , Glioblastoma/patología , Adolescente , Adulto , Biopsia , Encéfalo/patología , División Celular , Niño , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana EdadRESUMEN
The paper presents the results of immunohistochemical study of tenascin expression in 62 specimens of cerebellar medulloblastomas. All tumors can be classified as belonging to one of the 3 types of immunoreactivity: (1) tenascin-negative medulloblastomas, (2) tumors with extracellular and (3) intracellular expression of tenascin. Immunoreactivity was demonstrated in 61% of specimens. It perfectly matches the incidence of metastases. Medulloblastomas with intracellular tenascin expression demonstrated higher proliferative potential and are capable of expressing other oncoproteins (i.e. p 53, bcl-2). The data obtained in the study brought us to the conclusion that in patients with positive tenascin expression the prognosis is worse.
Asunto(s)
Neoplasias Cerebelosas/metabolismo , Meduloblastoma/metabolismo , Tenascina/metabolismo , Adolescente , Adulto , Biopsia , División Celular , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Neoplasias Cerebelosas/patología , Cerebelo/metabolismo , Cerebelo/patología , Niño , Preescolar , Citoplasma/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Meduloblastoma/patología , Persona de Mediana Edad , Proteínas Oncogénicas/metabolismoRESUMEN
p53 oncoprotein was studied in 80 astrocytic gliomas of the hemispheres and nuclear expression of this oncoprotein was found in 90% of the tumors this indicating high specificity of the reaction. A tendency to growing oncoprotein expression was found at different stages of malignant transformation showing feasibility of clonal expansion of cells with gene p53 mutation. High variability of the oncoprotein p53 immunoreactivity is characteristic of glioblastomas this suggesting genotypic polymorphism of gliomas of high grade malignancy. The lowest expression of the p53 oncoprotein was in gliosarcomas suggesting mechanism other than mutation. A stable link between the p53 oncoprotein expression and the proliferating cells nuclei antigen was not observed. This finding confirms an independent character of various progression features of the tumor.
Asunto(s)
Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Regulación Neoplásica de la Expresión Génica/fisiología , Proteína p53 Supresora de Tumor/metabolismo , Adolescente , Adulto , Anciano , Astrocitoma/genética , Astrocitoma/patología , Biopsia , Encéfalo/metabolismo , Encéfalo/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Niño , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Proliferating cell nuclear antigen (PCNA) was studied in 136 biopsies of brain astrocytic gliomas (AG) subdivided according to the degree of their malignancy into 3 groups: astrocytomas, anaplastic astrocytomas and glioblastomas. There were statistically significant differences in labelling index (LI) between these groups: 5.2, 34.1 and 49.5%, respectively. Mean LI of PCNA in the anaplastic astrocytomas was 6.5 times higher than in benign astrocytomas. Expression of PCNA in the tumor endotheliocytes was observed in 11 of 24 histologically benign astrocytomas and LI in these tumors was considerably higher than in the astrocytomas without endothelial expression. This indicates that proliferative processes in the tumor cells of AG and in the endotheliocytes of tumor vessels are interconnected.
Asunto(s)
Antígenos de Neoplasias/análisis , Astrocitoma/inmunología , Neoplasias Encefálicas/inmunología , Glioblastoma/inmunología , Antígeno Nuclear de Célula en Proliferación/análisis , Adolescente , Adulto , Anciano , Astrocitoma/patología , Biopsia , Neoplasias Encefálicas/patología , Niño , Femenino , Glioblastoma/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana EdadRESUMEN
Expression of the glial fibrillary acidic protein (GFAP) and S-100 protein was examined in 76 astrocytic gliomas (AG) with different degree of malignancy, which were subdivided into 4 groups: pilocytic astrocytoma, mixed astrocytoma, anaplastic astrocytoma and glioblastoma. Combined light-microscopical and immunohistochemical investigation detected several variants among different kinds of malignant AG that were distinguished by cytological composition and immunomorphology. Gemistocytic and polymorphic nuclear types were distinguished among anaplastic astrocytoma. Glioblastomas were subdivided into multiforme, isomorphic and gemistocytic variants. It was established that fractions of GFAP-negative cells occur in benign and malignant AG. Thus, the presence of population of immunonegative cells in AG is not a sign of high-grade tumor anaplasia. Groups of GFAP-positive cells around tumor vessels were found in malignant AG only.
Asunto(s)
Astrocitoma/química , Neoplasias Encefálicas/química , Proteína Ácida Fibrilar de la Glía/análisis , Proteínas S100/análisis , Adolescente , Adulto , Anciano , Astrocitoma/patología , Neoplasias Encefálicas/patología , Diferenciación Celular/fisiología , Niño , Preescolar , Femenino , Glioblastoma/química , Humanos , Inmunohistoquímica , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
33 embryonal neuroepithelial tumours of the cerebral hemispheres were examined light- and electron-microscopically, immunohistochemically. 4 types of tumours were distinguished: neuroblastoma, neuroepithelioma, ependymoblastoma and choroid carcinoma. Each type was characterised by its own pathohistological, immunohistochemical and ultrastructural features. Our results and literature data prove immunophenotypic and ultrastructural heterogeneity of embryonal neuroepithelial tumors of the cerebral hemispheres, in spite of some similarities in their pathohistological features.