RESUMO
The p90 ribosomal S6 kinase (RSK) family, a downstream target of Ras/extracellular signal-regulated kinase signaling, can mediate cross-talk with the mammalian target of rapamycin complex 1 pathway. As RSK connects two oncogenic pathways in gliomas, we investigated the protein levels of the RSK isoforms RSK1-4 in nontumoral brain (NB) and grade I-IV gliomas. When compared to NB or low-grade gliomas (LGG), a group of glioblastomas (GBMs) that excluded long-survivor cases expressed higher levels of RSK1 (RSK1hi ). No difference was observed in RSK2 median-expression levels among NB and gliomas; however, high levels of RSK2 in GBM (RSK2hi ) were associated with worse survival. RSK4 expression was not detected in any brain tissues, whereas RSK3 expression was very low, with GBM demonstrating the lowest RSK3 protein levels. RSK1hi and, to a lesser extent, RSK2hi GBMs showed higher levels of phosphorylated RSK, which reveals RSK activation. Transcriptome analysis indicated that most RSK1hi GBMs belonged to the mesenchymal subtype, and RSK1 expression strongly correlated with gene expression signature of immune infiltrates, in particular of activated natural killer cells and M2 macrophages. In an independent cohort, we confirmed that RSK1hi GBMs exclude long survivors, and RSK1 expression was associated with high protein levels of the mesenchymal subtype marker lysosomal protein transmembrane 5, as well as with high expression of CD68, which indicated the presence of infiltrating immune cells. An RSK1 signature was obtained based on differentially expressed mRNAs and validated in public glioma datasets. Enrichment of RSK1 signature followed glioma progression, recapitulating RSK1 protein expression, and was associated with worse survival not only in GBM but also in LGG. In conclusion, both RSK1 and RSK2 associate with glioma malignity, but displaying isoform-specific peculiarities. The progression-dependent expression and association with immune infiltration suggest RSK1 as a potential progression marker and therapeutic target for gliomas.
Assuntos
Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Proteínas de Membrana/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Transcriptoma/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/mortalidade , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Glioblastoma/genética , Glioblastoma/metabolismo , Glioma/genética , Glioma/imunologia , Glioma/secundário , Humanos , Imuno-Histoquímica , Células Matadoras Naturais/metabolismo , Macrófagos/metabolismo , Proteínas de Membrana/genética , Gradação de Tumores , Fosforilação , Isoformas de Proteínas , Proteínas Quinases S6 Ribossômicas 90-kDa/genética , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Transcriptoma/genéticaRESUMO
BACKGROUND: Peritoneal gliomatosis is characterized by the presence of miliary implants of mature glia on the peritoneum of patients with ovarian teratomas, usually immature. CLINICAL CASE: We report the case of a woman operated on 5 years earlier due to a right mature ovarian teratoma. When she was operated on due to left ovarian tumor she presented a miliary glial dissemination in omentum and peritoneum. CONCLUSION: The association of peritoneal gliomatosis ovarian teratomas is rare. Although the primary treatment and patient monitoring is focused on the teratoma, control should be maintained of peritoneal implants because of the possibility of malignancy. We believe it would be beneficial to establish a protocol for monitoring these lesions.
ANTECEDENTES: la gliomatosis peritoneal se caracteriza por la existencia de implantes miliares de tejido glial diseminados dentro de la cavidad abdominal de pacientes con teratomas ováricos, generalmente inmaduros. Caso clínico: paciente femenina intervenida cinco años antes de un teratoma maduro del ovario derecho, que al ser operada de un tumor en el ovario izquierdo se encontró diseminación miliar de tejido glial en el epiplón y el peritoneo. CONCLUSIÓN: la asociación de gliomatosis peritoneal con teratomas ováricos es infrecuente y, aunque el tratamiento principal y seguimiento de los pacientes está enfocado al teratoma deben controlarse los implantes peritoneales, por la posibilidad de malignización. Consideramos que sería benéfico establecer un protocolo para el seguimiento de pacientes con estas lesiones.
Assuntos
Glioma/secundário , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Teratoma/patologia , Adolescente , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Biomarcadores Tumorais/análise , Diferenciação Celular , Feminino , Glioma/química , Glioma/cirurgia , Humanos , Neoplasias Peritoneais/química , Neoplasias Peritoneais/cirurgia , Proteínas S100/análise , Vimentina/análiseRESUMO
BACKGROUND: Gliomatosis peritonei is the metastatic implantation of mature glial tissue within the peritoneal cavity of patients with ovarian teratomas. There is no clear guidance for how long these patients should be followed up. CLINICAL CASE: We report the follow-up imaging findings of a 33-year-old female with abdominal distension and abdominal pain and who was postoperatively diagnosed with immature ovarian teratoma with gliomatosis peritonei. CONCLUSIONS: Differentiation of peritoneal implants seems to be important for prognosis. Malignant transformations after several years cannot be excluded. Therefore, new studies will determine if it is necessary to create guidelines for the postsurgical monitoring of these patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Glioma/secundário , Neoplasias Ovarianas/patologia , Ovariectomia , Neoplasias Peritoneais/secundário , Teratoma/secundário , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Apendicectomia , Ascite/diagnóstico por imagem , Ascite/etiologia , Bleomicina/administração & dosagem , Cisplatino/administração & dosagem , Terapia Combinada , Etoposídeo/administração & dosagem , Feminino , Glioma/diagnóstico por imagem , Glioma/tratamento farmacológico , Hepatectomia , Humanos , Histerectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Imagem Multimodal , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Esplenectomia , Neoplasias Esplênicas/secundário , Neoplasias Esplênicas/cirurgia , Teratoma/diagnóstico por imagem , Teratoma/tratamento farmacológico , Teratoma/patologia , Teratoma/cirurgia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Local invasion is the hallmark of malignant glioma dissemination. Leptomeningeal dissemination, a serious complication of malignant gliomas, has been increasingly observed. To correlate the physiopathologic mechanisms and the magnetic resonance imaging patterns of neuroaxis dissemination, a classification of malignant glioma dissemination is proposed (Instituto de Neurologia de Curitiba Classification). METHODS: This classification includes the following patterns of dissemination: leptomeningeal (type I), nodular (type Ia), diffuse (type Ib); subependymal (type II); satellite (type IIIa, IIIb); and mixed (type IV), combination of 2 or more previous types. Of 138 patients with histologically confirmed gliomas treated between 2000 and 2004, 10 presented neuroaxis dissemination and were evaluated. RESULTS: The distribution of dissemination patterns was as follows: subependymal, 4 of 10; diffuse leptomeningeal, 1 of 10; nodular leptomeningeal, 1 of 10; and satellite, 4 of 10. Mean interval between primary tumor and dissemination was 4 months. The most frequent glioma dissemination risk factor was entering the ventricular system during surgery. CONCLUSIONS: Improvements in our diagnostic imaging capabilities have contributed to a better understanding of the patterns of malignant glioma dissemination. Using this information, we present a useful classification scheme, applicable to patients with neuroaxis dissemination, which will help standardize future discussions aimed at understanding these patterns of tumor spread.
Assuntos
Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/patologia , Glioma/classificação , Glioma/secundário , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/cirurgia , Feminino , Glioma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/secundário , Pessoa de Meia-Idade , Fatores de Risco , Análise de SobrevidaRESUMO
BACKGROUND: Frequency and clinical characteristics of brain tumors have been studied in several populations from different genetic backgrounds; their peculiarities in the Mexican mestizo population shed light on the descriptive and comparative epidemiologic analysis of the genetic participation in brain tumors. METHODS: To analyze the frequency of intracranial neoplasms at the National Institute of Neurology and Neurosurgery of Mexico between 1987 and 1994, demographic, clinical, surgical, and neuropathological records were reviewed and compared with other reports. Glioblastoma cases were followed to investigate survival and prognostic factors. RESULTS: In a seven-year period 1,776 patients with brain tumors were treated; 419 (24%) had pituitary adenoma; 586 (33%) had glioma. Of the latter, 165 had glioblastoma multiforme, representing 28% of all gliomas and 9% of all neoplasms. Mean survival for glioblastoma was 16 months and the longest mean survival was obtained in patients with radical neurosurgical resection plus radiotherapy and chemotherapy. Cumulative analysis showed that 41% of patients survived less than one year, 39% from 1 to 2 years, 12% from 2 to 3 years and 8% more than three years. Factors that showed prognostic significance were age, therapeutic approach, tumor size, and pre- and postoperative clinical status (p < 0.05). CONCLUSIONS: This study comprises the largest series on the frequency of brain tumors in a Latin American population. When compared with other studies, the proportion of glioma and glioblastoma among brain neoplasms was low whereas pituitary adenoma was high. Mean survival for glioblastoma was similar to other reports; in these patients, the overall therapeutic response is still far from satisfactory.