RESUMEN
Alteration of apoptosis is related with progression and recurrence of atypical meningiomas (AMs). However, no comprehensive study has been conducted regarding histone modification regulating apoptosis in AMs. This study aimed to determine the prognostic values of certain apoptosis-associated factors, and examine the role of histone modification on apoptosis in AMs. The medical records of 67 patients with AMs, as diagnosed during recent 13 yr, were reviewed retrospectively. Immunohistochemical staining was performed on archived paraffin-embedded tissues for pro-apoptotic factors (CASP3, IGFBP, TRAIL-R1, BAX, and XAF1), anti-apoptotic factors (survivin, ERK, RAF1, MDM2, and BCL2), and the histone modifying enzymes (MLL2, RIZ, EZH1, NSD2, KDM5c, JMJD2a, UTX, and JMJD5). Twenty-six (38.8%) patients recurred during the follow-up period (mean duration 47.7 months). In terms of time-to-recurrence (TTR), overexpression of CASP3, TRAIL-R1, and BAX had a longer TTR than low expression, and overexpression of survivin, MDM2, and BCL2 had a shorter TTR than low expression (P<0.05). Additionally, overexpression of MLL2, UTX, and JMJ5 had shorter TTRs than low expression, and overexpression of KDM5c had a longer TTR than low expression. However, in the multi-variate analysis of predicting factors for recurrence, low expression of CASP3 (P<0.001), and BAX (P<0.001), and overexpression of survivin (P=0.007), and MDM2 (P=0.037) were associated with recurrence independently, but any enzymes modifying histone were not associated with recurrence. Conclusively, this study suggests certain apoptosis-associated factors should be associated with recurrence of AMs, which may be regulated epigenetically by histone modifying enzymes.
Asunto(s)
Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/genética , Epigénesis Genética/genética , Regulación Neoplásica de la Expresión Génica/genética , Código de Histonas/genética , Histona Demetilasas/genética , N-Metiltransferasa de Histona-Lisina/genética , Estudios Longitudinales , Neoplasias Meníngeas/genética , Meningioma/genética , Recurrencia Local de Neoplasia/genéticaRESUMEN
The World Health Organization (WHO) classification of central nervous system (CNS) tumors incorporates morphology, cytogenetics, molecular genetics, and immunologic markers. Despite the relatively large number of CNS tumors with clonal chromosome abnormalities, only few studies have investigated cytogenetic abnormalities for CNS tumors in Korea. Thus, we investigated 119 CNS tumors by conventional G-banded karyotypes to characterize patterns of chromosomal abnormalities involving various CNS tumors, and 92.4% of them were cultured and karyotyped successfully. Totally, 51.8% of karyotypable CNS tumors showed abnormal cytogenetic results, including neuroepithelial tumors (75.0%), meningeal tumors (71.1%), pituitary adenomas (4.2%), schwannomas (44.4%), and metastatic tumors (100.0%). Glioblastomas had hyperdiploid, complex karyotypes, mainly involving chromosomes Y, 1, 2, 6, 7, 10, 12, 13, and 14. Monosomy 22 was observed in 56.4% of meningiomas. There was a significant increase in the frequencies of karyotypic complexity according to the increase of WHO grade between grades I and II (P=0.0422) or IV (P=0.0101). Abnormal karyotypes were more complex at high-grade tumors, suggesting that the karyotype reflects the biologic nature of the tumor. More detailed cytogenetic and molecular characterizations of CNS tumors contribute to better diagnostic criteria and deeper insights of tumorigenesis, eventually resulting in development of novel therapeutic strategies.
Asunto(s)
Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pueblo Asiatico/genética , Neoplasias del Sistema Nervioso Central/clasificación , Aberraciones Cromosómicas , Glioblastoma/genética , Cariotipificación , Corea (Geográfico) , Neoplasias Meníngeas/genética , Neurilemoma/genética , Neoplasias Hipofisarias/genéticaRESUMEN
The World Health Organization (WHO) classification of central nervous system (CNS) tumors incorporates morphology, cytogenetics, molecular genetics, and immunologic markers. Despite the relatively large number of CNS tumors with clonal chromosome abnormalities, only few studies have investigated cytogenetic abnormalities for CNS tumors in Korea. Thus, we investigated 119 CNS tumors by conventional G-banded karyotypes to characterize patterns of chromosomal abnormalities involving various CNS tumors, and 92.4% of them were cultured and karyotyped successfully. Totally, 51.8% of karyotypable CNS tumors showed abnormal cytogenetic results, including neuroepithelial tumors (75.0%), meningeal tumors (71.1%), pituitary adenomas (4.2%), schwannomas (44.4%), and metastatic tumors (100.0%). Glioblastomas had hyperdiploid, complex karyotypes, mainly involving chromosomes Y, 1, 2, 6, 7, 10, 12, 13, and 14. Monosomy 22 was observed in 56.4% of meningiomas. There was a significant increase in the frequencies of karyotypic complexity according to the increase of WHO grade between grades I and II (P=0.0422) or IV (P=0.0101). Abnormal karyotypes were more complex at high-grade tumors, suggesting that the karyotype reflects the biologic nature of the tumor. More detailed cytogenetic and molecular characterizations of CNS tumors contribute to better diagnostic criteria and deeper insights of tumorigenesis, eventually resulting in development of novel therapeutic strategies.
Asunto(s)
Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pueblo Asiatico/genética , Neoplasias del Sistema Nervioso Central/clasificación , Aberraciones Cromosómicas , Glioblastoma/genética , Cariotipificación , Corea (Geográfico) , Neoplasias Meníngeas/genética , Neurilemoma/genética , Neoplasias Hipofisarias/genéticaRESUMEN
We report the case of a 41-year-old man suffering for nine years from solitary fibrous tumour [SFT] of the tentorium cerebella. The tumour recurred twice, being characterized by a stepwise loss of antigenic profile and an enhanced proliferative activity. Meningeal SFTs are seldom described in literature. Malignant variants occur at peripheral sites but are not known within the central nervous system. Our case can provide deeper information about the tumour's behavior during long-term follow-up
Asunto(s)
Humanos , Masculino , Neoplasias de Tejido Fibroso/patología , Antígenos CD34 , Tomografía Computarizada por Rayos X , Literatura de Revisión como Asunto , Recurrencia , Imagen por Resonancia Magnética , Neoplasias Meníngeas/genética , Perfilación de la Expresión Génica , PronósticoRESUMEN
Tumors of the central nervous system account for approximately 9% of all primary neoplasm in humans, while tumors of covering elements, the meninges, account for 13-19% and constitute the second largest group of brain tumors. These are known to exhibit a variety of chromosomal abnormalities besides change in the expression level of certain oncogenes. Among oncogenes, bcl2, an anti-apoptotic factor and ROS1 that encodes a protein with a structure similar to the epidermal growth factor (EGF) and insulin receptor and has a tyrosine kinase activity, have been shown to be associated with many malignant tumors. In the present study we have analysed the expression of bcl2 using immuno-histochemistry and ROS1 expression by reverse-transcription coupled with polymerase chain reaction (RT-PCR) of the transcript using primers specific for the intra-cellular domain and then tried to correlate the findings with the subtype of the meningioma defined on the basis of histology. Out of the six bcl2 positive cases in our study, there were three transitional tumors, two fibroblastic and one recurrent meningioma subtype. bcl2 seemed to be more consistently expressed in the cytoplasm of spindle cell component of meningiomas. Thirteen meningiothelial meningiomas did not show any staining for bcl2. ROS1 gene expression could be detected in 4 tumors all of those were Grade-I meningothelial meningiomas. One of the malignant meningioma included in the study was clearly negative for bcl2 as well as ROS1. Thus bcl2 and ROS1 oncogene expression in meningiomas are not concurrent and neither can be ascribed to any histologic subtype or grade of tumor.
Asunto(s)
Expresión Génica , Genes bcl-2 , Humanos , Inmunohistoquímica , Neoplasias Meníngeas/genética , Meningioma/genética , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
We examined the alteration and expression of c-myc protooncogene in 11 human intracranial meningiomas using Southern blot, Northern blot and immunohistochemical techniques. Southern blot showed neither amplification nor rearrangement but Northern blot and immunohistochemical study revealed enhanced expression of the c-myc gene. Immunohistochemically, c-myc product was found in all of the 11 cases and seven of these cases showed an above moderate degree of immunoreaction in semiquantitative analysis. Loss of heterozygosity at IGLC2 locus on chromosome 22 was detected in four of the 8 informative cases. But extent and intensity of immunoreactivity did not correlated with loss of heterozygosity on chromosome 22. These genetic changes may play important roles in the pathogenesis of human intracranial meningioma.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Southern Blotting , Regulación Neoplásica de la Expresión Génica , Genes myc , Inmunohistoquímica , Neoplasias Meníngeas/genética , Meningioma/genéticaRESUMEN
Cytogenetic analysis of 4 cases of meningiomas from 3 male and 1 female patients is reported. One of male patients suffered from neurofibromatosis type 2. Histologically, the meningiomas were meningotheliomatous (1), transitional (2), and psammomatous (1). Chromosomal abnormalities were found in all cases with a karyotype 45,XY,-22, 45,XY,-16, 45,XX,-2, and 45,XY,t (15p;22q), respectively. Monosomy of chromosome 22 was detected only in the patient with neurofibromatosis type 2. These cytogenetic analysis demonstrates that variable clonal karyotype aberrations exist in meningiomas.
Asunto(s)
Adolescente , Adulto , Femenino , Humanos , Masculino , Aberraciones Cromosómicas , Neoplasias Meníngeas/genética , Meningioma/genética , Neurofibromatosis 2/genéticaRESUMEN
Quatro meningiomas primários humanos foram colocados em cultura e tiveram suas células analisadas citogenéticamente: 1 me meningioma transicional com número modal de 46 cromossomos (I), 2 meningiomas fibroblásticos ambos com número modal de 45 cromossomos (II e III) e 1 meningioma meningoendoteliomatoso com uma classe modal correspondente a 78 - 82 cromossomos (IV). A alteraçäo mais consistente encontrada em todos os tumores foi a monossomia total ou parcial do cromossomo 22 (I - 30%; II - 25%; III - 69% e IV - 30%). O tumor I apresentou também perda do cromossomo Y (80% das célulkas), além de outros marcadores nao identificados. O tumor II apresentou a deleçäo 12p12 - 12pter (65% das células) e del (19) (qter - p13:) (50% das células). O tumor III apresentou 3 marcadores recorrentes, näo identificados. O tumor IV apresentou um marcador acrocêntrico grande, näo identificado. Monossomias, trissomias e tetrassomias esporádicas também foram encontradas nesses tumores. Os pontos de quebra recorrentes foram comparados com os locais de sítios frágeis, pontos específicos de quebras neoplásicas, genes muito ativos de células diferenciadas e oncogenes, já descritos na literatura