El perfil molecular de los gliomas permite garantizar la precisión del diagnóstico, informar el pronóstico e identificar opciones de tratamiento. Esta revisión tiene como objetivo exponer que con la secuenciación de próxima generación (NSG) el diagnóstico de los pacientes con oligodendrogliomas puede ser más exacto. Además, con un dispositivo de diagnóstico in vitro, basado en la NSG (F1CDx), en el que se utilizan los bloques de parafina de gliomas para analizar hasta 395 genes relacionados con cáncer (incluido IDH 1 y 2), se puede también informar la pérdida de la totalidad del brazo corto del cromosoma 1 y del brazo largo del cromosoma 19 (codeleción 1p/19q), a diferencia de la hibridación fluorescente in situ (FISH) que detecta desde la más mínima deleción, lo cual los hace sensibles pero no específicos ya que el FISH es incapaz de distinguir entre la pérdida de la totalidad del brazo del cromosoma y una deleción focal. Esta distinción es importante ya que la sobrevida es inferior en tumores con deleción parcial en relación con los oligodendrogliomas, que tienen por definición la pérdida total de ambos cromosomas. Se hace también alusión a otras plataformas genómicas como GlioSeq y GLIO-DNA panel, que pueden cumplir la misma función. En conclusión, la F1CDx puede determinar con precisión 1p/19q con una concordancia del 96.7% frente a FISH. Los casos en que el FISH dio positivo y no concordaban con F1CDx, era porque no se trataba de oligodendrogliomas. F1CDx también analiza todos los genes que permiten la aproximación más exacta al diagnóstico de oligodendroglioma.
Molecular profiling of gliomas helps ensure diagnostic accuracy, inform prognosis, and identify treatment options. This review aims to show that with next generation sequencing (NGS) the diagnosis of patients with oligodendrogliomas can be more accurate. In addition, with an in vitro diagnostic device, based on NSG (F1CDx), in which glioma paraffin blocks are used to analyze up to 395 cancer-related genes (including IDH 1 and 2), it is also possible to report the loss of the entire short arm of chromosome 1 and the long arm of chromosome 19 (1p/19q codeletion), unlike fluorescence in situ hybridization (FISH) that detects even the slightest deletion, making them sensitive but not specific, as FISH is unable to distinguish between the loss of the entire arm of the chromosome and a focal deletion. This distinction is important since survival is lower in tumors with partial deletion compared to oligodendrogliomas, which by definition have the total loss of both chromosomes. Reference is also made to other genomic platforms such as GlioSeq and GLIO-DNA panel, which can fulfill the same function. In conclusion, the F1CDx can accurately determine 1p/19q with a concordance of 96.7% against FISH. The cases in which the FISH was positive and did not agree with F1CDx, it was because they were not oligodendrogliomas. F1CDx also analyzes all the genes that allow the most accurate approach to the diagnosis of oligodendroglioma.
O perfil molecular de gliomas ajuda a garantir a precisão do diagnóstico, informar o prognóstico e identificar as opções de tratamento. Esta revisão tem como objetivo mostrar que com o sequenciamento de próxima geração (NSG) o diagnóstico de pacientes com oligodendrogliomas pode ser mais preciso. Além disso, com um dispositivo de diagnóstico in vitro baseado em NSG (F1CDx), no qual blocos de parafina de glioma são usados para analisar até 395 genes relacionados ao câncer (incluindo IDH 1 e 2), também é possível relatar a perda do todo o braço curto do cromossomo 1 e o braço longo do cromossomo 19 (codeleção 1p/19q), ao contrário da hibridização fluorescente in situ(FISH) que detecta desde a menor deleção, o que os torna sensíveis, mas não específicos, pois o FISH é incapaz de distinguir entre a perda de todo o braço do cromossomo e uma deleção focal. Essa distinção é importante, pois a sobrevida é menor nos tumores com deleção parcial em relação aos oligodendrogliomas, que por definição apresentam a perda total de ambos os cromossomos. Também é feita referência a outras plataformas genômicas, como GlioSeq e painel GLIO-DNA, que podem cumprir a mesma função. Em conclusão, o F1CDx pode determinar com precisão 1p/19q com uma concordância de 96,7% versus FISH. Os casos em que FISH foi positivo e não concordaram com F1CDx, foi porque não eram oligodendrogliomas. O F1CDx também analisa todos os genes que permitem a abordagem mais precisa para o diagnóstico de oligodendroglioma.
Subject(s)Humans , Glioma , Oligodendroglioma , Survival , In Vitro Techniques , Diagnosis , Neoplasms
Resumen Los tumores cerebrales se caracterizan por su gran morbilidad y mortalidad. La gran mayoría corresponde a tumores secundarios (metástasis). Dentro de los tumores primarios del sistema nervioso central, los gliomas corresponden al 30% de éstos. En EEUU, entre el 2007-2011, se estima una incidencia aproximada de 21,4 casos por 100.000 habitantes. Los recientes avances en la comprensión molecular de la biología de estos tumores han permitido mejorar sustancialmente su clasificación, posibilitando realizar un mejor correlato con los desenlaces clínicos y el pronóstico. En esta línea, hoy en día es posible estratificar a los pacientes por riesgo y entregar tratamientos capaces de prolongar la sobrevida global entre 5-7 años, para los gliomas grado II y III. El presente consenso, elaborado por un panel multidisciplinario de expertos de diversas sociedades científicas chilenas y, por tanto, de todas las especialidades involucradas en el manejo médico-quirúrgico de las personas portadoras de gliomas cerebrales. A la luz de este nuevo conocimiento desarrollado al alero de la oncología molecular, esta propuesta ofrece un insumo de utilidad clínica real, que, articulado a una revisión actualizada en relación con el tratamiento y seguimiento de estos pacientes, permite entender la relevancia de estos biomarcadores en el manejo de precisión de la enfermedad. Cabe señalar que, este manuscrito emerge de la misma fuerza de trabajo, que elaboró el Protocolo Clínico de Gliomas del Adulto 2019, publicado por el Ministerio de Salud, y que ha diferencia de esta, que ofrece los detalles clínicos-operativos, como flujogramas y dosis, nuestra revisión intenta relevar los avances imagenológicos y moleculares y como estos impactan en el manejo actual de la enfermedad.
Brain tumors are characterized by high morbidity and mortality. The vast majority correspond to secondary tumors (metastasis). On the other hand, within the primary tumors of the central nervous system, gliomas correspond to 30% of these. In the US, between 2007-2011, an approximate incidence of 21.4 cases per 100,000 inhabitants was estimated. Recent advances in the molecular understanding of the biology of these tumors have made it possible to substantially improve their classification, allowing a better correlation with clinical outcomes and prognosis. Along these lines, today, it is possible to stratify patients by risk and deliver treatments capable of prolonging global survival between 5-7 years, for grade II and III gliomas. The present consensus, prepared by a multidisciplinary panel of experts from various Chilean scientific societies and, therefore, from all the specialties involved in the medical and surgical therapy. Enlightened from the molecular oncology, this proposal offers an input of clinical utility, which, together with an updated review in relation to the treatment and follow-up of these patients, allows us to understand the relevance of these biomarkers in precision disease management. It should be noted that this manuscript emerges from the same work force, which prepared the Clinical Protocol for Adult Gliomas 2019, published by the Ministry of Health, and that differs from it, which offers clinical-operative details, such as flowcharts and dose, our review attempts to reveal imaging and molecular advances and how they impact the current management of the disease.
Subject(s)Humans , Brain Neoplasms/diagnosis , Brain Neoplasms/therapy , Glioma/diagnosis , Glioma/therapy , Chile , Consensus
RESUMO O objetivo deste relato foi descrever o caso de um paciente submetido à craniotomia, acordado, para a ressecção neurocirúrgica de um glioma e a avaliação linguística pré-operatória, intraoperatória e pós-operatória. Paciente do gênero masculino, 27 anos, escolaridade nível superior incompleto, apresentando vômitos, confusão mental e crise convulsiva tônico-clônica. Após a avaliação do paciente pela equipe e devidas orientações pré-operatórias, a proposta de excisão da lesão em estado de vigília foi esclarecida e aceita. Ao iniciar o procedimento, os campos foram ajustados para manter as vias aéreas e os olhos acessíveis para mapeamento com estimulação elétrica e avaliação da linguagem no período intraoperatório. Devido à localização do tumor próximo à área motora da fala, foram propostas tarefas para a avaliação da linguagem em quatro momentos: pré-operatório, intraoperatório, pós-operatório imediato e pós-operatório mediato. As habilidades linguísticas testadas nas quatro avaliações foram: compreensão e expressão da linguagem oral, transposição linguística, linguagem associativa, nomeação, discriminação visual, fluência e organização da sintaxe. Com o objetivo de controlar e eliminar o efeito de aprendizagem da testagem, foram solicitadas as mesmas tarefas, porém, com diferentes conteúdos para a testagem das habilidades nas quatro fases. A cirurgia com o paciente acordado permitiu a ressecção completa e segura do tumor, sem prejuízo motor ou linguístico. O engajamento da equipe, a interação interdisciplinar e o planejamento cirúrgico detalhado constituem um pilar para o bom resultado de um procedimento tão complexo e delicado.
ABSTRACT The purpose of this report is to describe the case of a patient who underwent awake craniotomy for neurosurgical resection of a glioma and pre, intra and postoperative linguistic assessment. Male patient, 27 years old, incomplete higher education presenting vomiting, mental confusion and tonic-clonic seizures. After the evaluation of the patient by the team and due preoperative guidance, the proposal of excision of the lesion while awake was clarified and accepted. At the start of the procedure, the fields were adjusted to keep the airway and eyes accessible for mapping with electrical stimulation and intraoperative language assessment. Due to the location of the tumor close to the speech motor area, tasks were proposed for the assessment of language in four moments: preoperative, intraoperative, immediate postoperative and mediate postoperative. The language skills tested in the four assessments were: comprehension and expression of oral language, linguistic transposition, associative language, naming, visual discrimination, fluency and syntax organization. In order to control and eliminate the learning effect of testing, the same tasks were requested, but with different contents for testing skills in the four phases. Surgery with the patient awake allowed the complete and safe resection of the tumor, without motor or linguistic damage to the patient. Team engagement, interdisciplinary interaction and detailed surgical planning constitute the pillar for the good result of such a complex and delicate procedure
Subject(s)Humans , Male , Adult , Skull/surgery , Central Nervous System Neoplasms/surgery , Craniotomy/methods , Glioma/surgery , Language Tests , Electric Stimulation
Glioma is a primary brain tumor with high incidence rate. High-grade gliomas (HGG) are those with the highest degree of malignancy and the lowest degree of survival. Surgical resection and postoperative adjuvant chemoradiotherapy are often used in clinical treatment, so accurate segmentation of tumor-related areas is of great significance for the treatment of patients. In order to improve the segmentation accuracy of HGG, this paper proposes a multi-modal glioma semantic segmentation network with multi-scale feature extraction and multi-attention fusion mechanism. The main contributions are, (1) Multi-scale residual structures were used to extract features from multi-modal gliomas magnetic resonance imaging (MRI); (2) Two types of attention modules were used for features aggregating in channel and spatial; (3) In order to improve the segmentation performance of the whole network, the branch classifier was constructed using ensemble learning strategy to adjust and correct the classification results of the backbone classifier. The experimental results showed that the Dice coefficient values of the proposed segmentation method in this article were 0.909 7, 0.877 3 and 0.839 6 for whole tumor, tumor core and enhanced tumor respectively, and the segmentation results had good boundary continuity in the three-dimensional direction. Therefore, the proposed semantic segmentation network has good segmentation performance for high-grade gliomas lesions.
Subject(s)Humans , Attention , Glioma/diagnostic imaging , Magnetic Resonance Imaging/methods , Semantics
OBJECTIVE@#To explore the effect and mechanism of down-regulating lncRNA TTTY15 targeting miR-4500 on the proliferation, apoptosis, migration and invasion of A172 glioma cells.@*METHODS@#The difference in TTTY15 expression between the glioma cells and tissue was determined with a qRT-PCR method. Complementary binding sites of TTTY15 and miR-4500 were predicted with Starbase software, and the targeting relationship was validated with a luciferase reporter system. A172 glioma cells were divided into Control, si-NC (transfected with control siRNA), si-TTTY15 (transfected with TTTY15 siRNA), si-TTTY15+Anti-miR-NC (co-transfected with TTTY15 siRNA and inhibitor control) and si-TTTY15+Anti-miR-4500 (co-transfected with TTTY15 siRNA and miR-4500 inhibitor) groups. Proliferation, apoptosis, migration and invasion, and the expression of Bax, Bcl-2, MMP-2 and MMP-9 proteins of the A172 glioma cells were respectively detected with CCK-8, flow cytometry, Transwell chamber and Western blotting assays.@*RESULTS@#The expression of TTTY15 in glioma cells and glioma tissues have both increased. The expression levels of TTTY15 and miR-4500 in glioma tissues were inversely correlated. TTTY15 and miR-4500 are mutually targeted. Compared with those of the Control and si-NC groups, the glioma cells in the si-TTTY15 group showed increased level of miR-4500, decreased survival rate, increased apoptosis rate, enhanced cell migration and invasion, increased expression of Bax protein, and decreased expression of Bcl-2, MMP-2 and MMP-9 proteins (P<0.05). Compared with those of the si-TTTY15+Anti-miR-NC group, the A172 glioma cells in the si-TTTY15+Anti-miR-4500 group showed decreased level of miR-4500, increased cell survival rate, decreased apoptosis rate, enhanced cell migration and invasion, decreased expression of Bax protein, and increased expression of Bcl-2, MMP-2, and MMP-9 proteins (P<0.05).@*CONCLUSION@#Down-regulating TTTY15 targeting miR-4500 can inhibit the proliferation, migration, invasion and induce apoptosis of the A172 glioma cells.
Subject(s)Humans , Apoptosis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Down-Regulation , Gene Expression Regulation, Neoplastic , Glioma/genetics , MicroRNAs/genetics , RNA, Long Noncoding
Objective To investigate the relationship between the expression of glutathione peroxidase(GPX)genes and the clinical prognosis in glioma patients,and to construct and evaluate the model for predicting the prognosis of glioma. Methods The clinical information and GPX expression of 663 patients,including 153 patients of glioblastoma(GBM)and 510 patients of low-grade glioma(LGG),were obtained from The Cancer Genome Atlas(TCGA)database.The relationship between GPX expression and patient survival was analyzed.The key GPX affecting the prognosis of glioma was screened out by single- and multi-factor Cox's proportional-hazards regression models and validated by least absolute shrinkage and selection operator(Lasso)regression.Finally,we constructed the model for predicting the prognosis of glioma with the screening results and then used concordance index and calibration curve respectively to evaluate the discrimination and calibration of model. Results Compared with those in the control group,the expression levels of GPX1,GPX3,GPX4,GPX7,and GPX8 were up-regulated in glioma patients(all P<0.001).Moreover,the expression levels of other GPX except GPX3 were higher in GBM patients than in LGG patients(all P<0.001).The Kaplan-Meier curves showed that the progression-free survival of GBM with high expression of GPX1(P=0.013)and GPX4(P=0.040),as well as the overall survival,disease-specific survival,and progression-free survival of LGG with high expression of GPX1,GPX7,and GPX8,was shortened(all P<0.001).GPX7 and GPX8 were screened out as the key factors affecting the prognosis of LGG.The results were further used to construct a nomogram model,which suggested GPX7 was the most important variable.The concordance index of the model was 0.843(95%CI=0.809-0.853),and the calibration curve showed that the predicted and actual results had good consistency. Conclusion GPX7 is an independent risk factor affecting the prognosis of LGG,and the nomogram model constructed with it can be used to predict the survival rate of LGG.
Subject(s)Humans , Brain Neoplasms , Glioblastoma , Glioma/diagnosis , Glutathione Peroxidase/metabolism , Peroxidases , Prognosis , Proportional Hazards Models
OBJECTIVE@#To explore the effect of atorvastatin (AVT) on biological behaviors and the miR-146a/PI3K/Akt signaling pathway in human glioma cells.@*METHODS@#Human glioma U251 cells were treated with 8.0 μmol/L AVT or transfected with a miR-146a inhibitor or a negative control fragment (miR-146a NC) prior to AVT treatment. RT-PCR was used to detect miR-146a expression in the cells, and the changes in cell proliferation rate, apoptosis, cell invasion and migration were detected using MTT assay, flow cytometry, and Transwell assay. Western blotting was performed to detect the changes in cellular expressions of proteins in the PI3K/Akt signaling pathway.@*RESULTS@#AVT treatment for 48 h resulted in significantly increased miR-146a expression and cell apoptosis (P < 0.01) and obviously lowered the cell proliferation rate, invasion index, migration index, and expressions of p-PI3K and p-Akt protein in U251 cells (P < 0.01). Compared with AVT treatment alone, transfection with miR-146a inhibitor prior to AVT treatment significantly reduced miR-146a expression and cell apoptosis (P < 0.01), increased the cell proliferation rate, promoted cell invasion and migration, and enhanced the expressions of p-PI3K and p-Akt proteins in the cells (P < 0.01); these effects were not observed following transfection with miR-146a NC group (P>0.05).@*CONCLUSION@#AVT can inhibit the proliferation, invasion and migration and promote apoptosis of human glioma cells possibly by up-regulating miR-146a expression and inhibiting the PI3K/Akt signaling pathway.
Subject(s)Humans , Apoptosis , Atorvastatin/pharmacology , Cell Line, Tumor , Cell Proliferation , Glioma/pathology , MicroRNAs/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction
OBJECTIVE@#To investigate the effect of interference of P2X4 receptor expression in tumor-associated macrophages (TAMs) on invasion and migration of glioma cells.@*METHODS@#C57BL/6 mouse models bearing gliomas in the caudate nucleus were examined for glioma pathology with HE staining and expressions of Iba-1 and P2X4 receptor with immunofluorescence assay. RAW264.7 cells were induced into TAMs using conditioned medium from GL261 cells, and the changes in mRNA expressions of macrophage polarization-related markers and the mRNA and protein expressions of P2X4 receptor were detected with RT-qPCR and Western blotting. The effect of siRNA-mediated P2X4 interference on IL-1β and IL-18 mRNA and protein expressions in the TAMs was detected with RT-qPCR and Western blotting. GL261 cells were cultured in the conditioned medium from the transfected TAMs, and the invasion and migration abilities of the cells were assessed with Transwell invasion and migration experiment.@*RESULTS@#The glioma tissues from the tumor-bearing mice showed a significantly greater number of Iba-1-positive cells, where an obviously increased P2X4 receptor expression was detected (P=0.001), than the brain tissues of the control mice (P < 0.001). The M2 macrophage markers (Arg-1 and IL-10) and M1 macrophage markers (iNOS and TNF-α) were both significantly up-regulated in the TAMs derived from RAW264.7 cells (all P < 0.01), but the up-regulation of the M2 macrophage markers was more prominent; the expression levels of P2X4 receptor protein and mRNA were both increased in the TAMs (P < 0.05). Interference of P2X4 receptor expression significantly lowered the mRNA(P < 0.01)and protein (P < 0.01, P < 0.05)expression levels of IL-1β and IL-18 in the TAMs and obviously inhibited the ability of the TAMs to promote invasion and migration of the glioma cells (P < 0.05).@*CONCLUSION@#Interference of P2X4 receptor in the TAMs suppresses the migration and invasion of glioma cells possibly by lowering the expressions of IL-1β and IL-18.
Subject(s)Animals , Mice , Culture Media, Conditioned , Glioma , Interleukin-18 , Mice, Inbred C57BL , RNA, Messenger , Receptors, Purinergic P2X4/metabolism , Tumor-Associated Macrophages
OBJECTIVE@#To study the correlation between immune cell infiltration in colorectal cancer tissue and clinical prognosis and to explore the levels of some immune cell genes for predicting the prognosis of patients with glioma colorectal cancer.@*METHODS@#In this study, we extracted colorectal cancer data from the cancer genome atlas (TCGA). Based on a deconvolution algorithm (called CIBERSORT) and clinically annotated expression profiles, the analysis assessed the infiltration patterns of 22 immune cells in colorectal cancer tissue to determine the association between each cell type and survival. Differences in five-year survival rate effectively illustrate the clinical prognostic value of each immune cell proportion in colorectal cancer, using a bar graph, correlation-based heatmap to represent the proportion of immune cells in each colorectal cancer sample.@*RESULTS@#A total of 473 colorectal cancer tissues and 41 normal control tissues were extracted from the TCGA database, and the comparative analysis showed that there were differences in the proportion of various TIICs in colorectal cancer tissues, which could characterize individual differences and have prognostic value. Among the cell subsets studied, the proportions of memory B cells, plasma cells, CD4+ T cells, natural killer (NK) cells, M0 macrophages, M2 macrophages, and activated mast cells were significantly different between normal and cancer tissues. Resting NK cells, CD8+ T cells, and plasma cells were associated with T phase, activated dendritic cells were associated with N phase, and eosinophils, M1 macrophages, and activated mast cells were associated with M phase. Survival analysis showed that activated dendritic cells were positively associated with five-year survival rate in colorectal cancer patients. Naive CD4+ T cells were inversely associated with five-year survival rate.@*CONCLUSION@#There are different degrees of immune cell infiltration in colorectal cancer tissues, and these differences may be important determinants of prognosis and treatment response. We conducted a new gene expression-based study of immune cell subtype levels and prognosis in colorectal cancer, which has potential clinical prognostic value in colorectal cancer patients.
Subject(s)Humans , CD8-Positive T-Lymphocytes , Colorectal Neoplasms/genetics , Glioma , Macrophages , Prognosis
Objective: To investigate the clinicopathological features of pediatric diffuse midline glioma with H3K27 alteration and to analyze their relationship with prognosis. Methods: Forty-one cases of childhood diffuse midline glioma with H3K27 alteration were collected at Children's Hospital of Fudan University (39 cases) and Xi'an Children's Hospital (2 cases), from July 2016 to July 2020. The clinical manifestations, imaging data, histopathology, immunohistochemical phenotype and molecular genetics features, tumor size, site and histological grading were evaluated. Results: Among the 41 cases, 21 were males and 20 females, the age of onset was 3-14 years, the average and median age was 7.6 years and 7.0 years, respectively. The tumor sites were brain stem (n=36) and other locations (n=5). The clinical manifestations were dizziness, gait disturbance, and limb weakness, etc. The MRI features were variable. The histology varied from low-grade to high-grade glioma with neuron differentiation. Immunohistochemistry showed that the tumor cells expressed H3K27M, GFAP, and Olig2. Genetic study showed that 76% (16/21) of tumors had H3F3A gene mutation, mostly accompanied by TP53 (62%, 13/21) missense mutation; five tumors (24%, 5/21) had HIST1H3B gene mutation, accompanied by missense mutations in ACVR1 and PI3K pathway-related gene PIK3CA (4/5) and PIK3R1 (1/5) mutations. The prognosis was dismal with only one alive and others died. The average and median overall survival time was 7 months and 4 months, respectively. Cox multivariate regression analysis showed that age, tumor location, radiologically maximum tumor diameter, histologic grading, and surgical methods were not significantly associated with overall survival rate (P>0.05). Conclusions: Pediatric diffuse midline gliomas with H3K27 alteration have unique clinicopathological and genetic characteristics. The prognosis is poor. The tumor location and histopathologic grading are not related to prognosis. New specific drugs and comprehensive treatment are needed to improve the prognosis.
Subject(s)Adolescent , Child , Child, Preschool , Female , Humans , Male , Brain Neoplasms/genetics , Glioma/pathology , Histones/genetics , Phosphatidylinositol 3-Kinases/genetics , Prognosis
Objective: To investigate the clinicopathological features and treatment strategies of pituicytoma. Methods: Twenty-one cases of pituicytoma were collected at the First Affiliated Hospital of Nanjing Medical University and Jinling Hospital, Nanjing, China from 2009 to 2020. The clinical data of 21 pituicytoma patients was retrospectively analyzed, and the relevant literature was reviewed. Results: Twenty-one patients aged 4 to 68 years, including 8 males and 13 females. All patients underwent surgical treatment. Histologically, the tumor was consisted almost entirely of elongate, bipolar spindle cells arranged in a fascicular or storiform pattern. Mitotic figures were rare. Immunohistochemically, tumor cells were diffusely positive for S-100 protein (21/21), vimentin (15/15) and TTF1 (14/14), while they were weakly or focally positive for GFAP (13/16) and EMA (6/12). CKpan was negative in all cases and Ki-67 proliferation index was low (<5%). Among the 18 patients with follow-up, all survived and 2 relapsed after surgery. Conclusions: Pituicytoma is a rare low-grade glioma of the sellar area. It is easily confused with other sellar tumors. Preoperative diagnosis is difficult. It needs to be confirmed by histopathology and immunohistochemistry. Microsurgery is the main treatment method at present.
Subject(s)Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Craniopharyngioma , Glioma/pathology , Immunohistochemistry , Pituitary Neoplasms/pathology , Retrospective Studies
Objective: To study the effects of Homeobox C10 (HOXC10) on biological characteristics such as migration, invasion and proliferation of glioma cancer cells and to explore the role of HOXC10 gene in glioma microenvironment. Methods: The expression level of HOXC10 in high grade glioma (glioblastoma) and low grade glioma and its effect on patient survival were analyzed by using The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) database. Hoxc10-siRNA-1, HOXC10-siRNA-2 and siRNA negative control (NC) were transfected into U251 cells according to the operation instructions of HOXC10-siRNA transfection. 100 ng/ mL recombinant protein chemokine ligand 2 (reCCL2) was added into the transfection group, and was labeled as HOXC10-siRNA-1+ reCCL2 and HOXC10-siRNA-2+ reCCL2 groups. The expressions of HOXC10 mRNA and target protein in each group was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and western blot. The proliferation ability of cells in each group was detected by cell counting kit 8 (CCK8) method. The migration ability of cells was detected by Transwell assay and Nick assay, and cell apoptosis was detected by flow cytometry. The expression of chemokines in each group was detected by multiple factors. Co-incubation assays were performed to determine the role of HOXC10 and chemokine ligand 2 (CCL2) in recruiting and polarizing tumor-associated macrophages (M2-type macrophages). Results: The median expression level of HOXC10 in high grade gliomas was 8.51, higher than 1.00 in low grade gliomas (P<0.001) in TCGA database. The median expression level of HOXC10 in high grade gliomas was 0.83, higher than 0.00 in low grade gliomas (P=0.002) in CGGA database. The 5-year survival rate of patients with high HOXC10 expression in TCGA database was 28.2%, lower than 78.7% of those with low HOXC10 expression (P<0.001), and the 5-year survival rate of patients with high HOXC10 expression in CGGA database was 20.3%, lower than 58.0% of those with low HOXC10 expression (P<0.001). The numbers of cell migration in HOXC10-siRNA-1 group and HOXC10-siRNA-2 group were (45±3) and (69±4) respectively, lower than (159±3) in NC group (P<0.05). The cell mobility of HOXC10-siRNA-1 group and HOXC10-siRNA-2 group at 48 hours were (15±2)% and (28±4)% respectively, lower than (80±5)% of NC group (P<0.05). The expressions of vimentin in HOXC10-siRNA-1 group and HOXC10-siRNA-2 group were (141 740.00±34 024.56) and (94 655.00±5 687.97), N-cadherin were (76 810.00±14.14) and (94 254.00±701.45), β-catenin were (75 786.50±789.84) and (107 296.50±9 614.53), lower than (233 768.50±34 114.37), (237 154.50±24 715.50) and (192 449.50±24 178.10) of NC group (P<0.05). The A value of HOXC10-siRNA-1 group and HOXC10-siRNA-2 group were (0.44±0.05) and (0.32±0.02) at 96 hours, lower than 0.92±0.12 of NC group (P<0.05). The apoptosis rates of HOXC10-siRNA-1 group and HOXC10 siRNA-2 group were (10.23±1.24)% and (13.81±2.16)%, higher than (4.60±0.07)% of NC group (P<0.05). The expression levels of CCL2 in U251 cells in HOXC10-siRNA-1 and HOXC10-siRNA-2 groups were (271.63±44.27) and (371.66±50.21), lower than (933.93±29.84) in NC group (P<0.05). The expression levels of CCL5 (234.81±5.95 and 232.62±5.72), CXCL10 (544.13±48.14 and 500.87±15.65) and CXCL11 (215.75±15.30 and 176.18±16.49) in HOXC10-siRNA-1 and HOXC10-siRNA-2 groups were higher than those in NC group (9.98±0.71, 470.54±18.84 and 13.55±0.73, respectively, P<0.05). The recruited numbers of CD14(+) THP1 in HOXC10-siRNA-1 and HOXC10-siRNA-2 groups were (159.33±1.15) and (170.67±1.15), respectively, lower than (360.00±7.81) in NC group (P<0.05), while addition of reCCL2 promoted the recruitment of CD14(+) THP1 cells (287.00±3.61 and 280.67±2.31 in HOXC10-siRNA-1+ reCCL2 group and HOXC10-siRNA-2+ reCCL2 group, respectively, P<0.05). The expressions level of M2-type macrophage-related gene TGF-β in HOXC10-siRNA-1 group and HOXC10-siRNA-2 group were (0.30±0.02) and (0.28±0.02), respectively, lower than (1.06±0.10) in NC group (P<0.05). The expressions level of M1-related gene NOS2 in HOXC10-siRNA-1 and HOXC10-siRNA-2 were (11 413.95±1 911.85) and (5 894.00±945.21), respectively, higher than (13.39±4.32) in NC group (P<0.05). Conclusions: The expression of HOXC10 in glioma is high and positively correlated with the poor prognosis of glioma patients. Knockdown of HOXC10 can inhibit the proliferation, migration and metastasis of human glioma U251 cells. HOXC10 may play an immunosuppressive role in glioma microenvironment by promoting the expression of CCL2 and recruiting and polarizing tumor-associated macrophages (M2 macrophages).
Subject(s)Humans , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Genes, Homeobox , Glioma/pathology , Homeodomain Proteins/metabolism , Neoplasm Invasiveness/genetics , Tumor Microenvironment
Introducción. El xantoastrocitoma pleomórfico es una lesión glial de bajo grado de malignidad (grado II), puede presentar transformación maligna progresando a xantoastrocitoma pleomórfico anaplásico o glioblastoma multiforme, clasificados en grado III y IV, respectivamente, de acuerdo con la OMS. El glioblastoma epitelioide es un subtipo morfológico poco común del glioblastoma, de comportamiento agresivo, asociado a recurrencia temprana y compromiso leptomeníngeo. Presentación del caso. Se describe un reporte de caso de paciente femenina de 13 años con hallazgos de xantoastrocitoma pleomórfico anaplásico asociado a glioblastoma epitelioide, neoplasia poco frecuente que suele presentarse en la población pediátrica y en los adultos jóvenes. Discusión. El diagnóstico de glioblastoma epitelioide constituye un desafío, solo se han reportado unas pocas series pequeñas en la población adulta y pediátrica. Conclusión. Los hallazgos imagenológicos en las dos entidades son similares y comparten características histopatológicas e incluso algunos hallazgos moleculares superpuestos, lo cual dificulta su diferenciación, por lo que continúa siendo de gran controversia si se presentan conjuntamente o si el xantoastrocitoma pleomórfico anaplásico es un precursor del glioblastoma epitelioide.
Introduction. Pleomorphic xanthoastrocytoma is a glial lesion with low grade of malignancy (grade II), it can present malignant transformation progressing to anaplastic pleomorphic xanthoastrocytoma or glioblastoma multiforme, classified as grade III and IV, respectively, according to the WHO. Epithelioid glioblastoma is a rare morphological subtype of glioblastoma, with aggressive behavior, associated with early recurrence and leptomeningeal compromise. Case Presentation. Case report of a 13-year-old female patient with findings of anaplastic pleomorphic xanthoastrocytoma associated with epithelioid glioblastoma, a rare neoplasm that usually occurs in the pediatric population and in young adults. Discussion. The diagnosis of epithelioid glioblastoma is challenging, only a few small series have been reported in the adult and pediatric population. Conclusion. The imaging findings in the two entities are similar and share histopathological characteristics and even some overlapping molecular findings, which makes their differentiation difficult. For this reason, there is still a great controversy whether these entities are present continuously or whether the anaplastic pleomorphic xanthoastrocytoma is a precursor of epithelioid glioblastoma.
Introdução. O xantoastrocitoma pleomórfico é uma lesão glial de baixo grau de malignidade (grau II), pode apresentar transformação maligna progredindo para xantoastrocitoma pleomórfico anaplásico ou glioblastoma multiforme, classificados como grau III e IV, respectivamente, de acordo com a OMS. O glioblastoma epitelióide é um subtipo morfológico raro de glioblastoma, com comportamento agressivo, associado a recorrência precoce e envolvimento leptomeníngeo. Apresentação do caso. É descrito um relatório de caso de uma paciente feminina de 13 anos com achados de xantoastrocitoma pleomórfico anaplásico associado ao glioblastoma epitelióide, uma neoplasia rara que geralmente ocorre na população pediátrica e em adultos jovens. Discussão. O diagnóstico do glioblastoma epitélioide é desafiador, apenas algumas pequenas séries foram reportadas na população adulta e pediátrica. Conclusão. As descobertas imagiológicas nas duas entidades são semelhantes e compartilham características histopatológicas e, até mesmo, algumas descobertas moleculares sobrepostas, o que dificulta sua diferenciação, portanto permanece controverso se ocorrem juntas ou se o xantoastrocitoma pleomórfico anaplásico é um precursor do glioblastoma epitélioide.
Subject(s)Brain Neoplasms , Astrocytoma , Glioblastoma , Diagnosis, Differential , Glioma
Resumen La mutación puntual V600E del gen BRAF juega un papel fundamental en la tumorigénesis de muchos gliomas. La inhibición de su producto forma parte de terapias innovadoras emergentes en los últimos años. Conocer el rol de estos tratamientos resulta imprescindible. El objetivo del trabajo fue describir la respuesta clínico-radiológica en niños con gliomas BRAF V600E mutado tratados con inhibidores BRAF. Para ello se realizó un estudio descriptivo y retrospectivo en pacientes menores de 16 años con gliomas BRAF V600E mu tado que recibieron vemurafenib o dabrafenib en el Hospital Garrahan. Trece pacientes tratados en los últimos 7 años fueron incluidos: 9 gliomas de bajo grado y 4 de alto grado. La mediana de edad al diagnóstico fue 8.6 años (0.89-14.04) y del comienzo del inhibidor 11.62 años (3.64-15.42). Inicialmente, todos habían realizado tratamiento quirúrgico, y 12/13 recibieron previamente otra terapia: 11 quimioterapia (eventualmente hasta 4 líneas distintas) y 4 radioterapia. Con la terapia dirigida, 10 pacientes tuvieron una disminución tumoral mayor o igual al 25%, quedando evidenciada en 7 niños la mejor respuesta dentro de los 6 meses del inicio. Hubo 4 progresados intratratamiento (todos alto grado), y 2 progresados prontamente luego de suspender el inhibidor (ambos bajo grado). Cinco presentaron efectos adversos grado 3-4, con recuperación ad-integrum. Se describe una buena y sostenida respuesta clínico-radiológica, con tolerancia aceptable, en pacientes con gliomas de bajo grado BRAF V600E mutado tratados con inhibidores BRAF V600E . En contraste, la respuesta en pacientes con gliomas de alto grado fue intermedia y de poca duración, con progresión tumoral precoz.
Abstract The BRAF V600E point mutation plays a key role in the tumorigenesis of many gliomas. Inhibiting its product is part of the innovative therapies emerging in recent years. Knowing the role of these treatments is essential. The aim of this experience was to describe the clinical-radiological response of pediatric BRAF V600E mutated gliomas treated with BRAF inhibitors. To this end, a descriptive and retrospective study was performed in patients under 16 years of age with BRAF V600E gliomas, who received vemurafenib or dabrafenib at Hospital Garrahan. Thirteen patients treated in the last 7 years were included: 9 were low-grade and 4 high-grade gliomas. The median age at diagnosis was 8.6 years (0.89-14.04) and at start of targeted therapy was 11.62 years (3.64-15.42). All patients had previously a surgical procedure, and 12/13 had received another therapy prior BRAF inhibition: 11 chemotherapy (in one case, up to 4 different protocols) and 4 radiotherapy. Under targeted therapy, tumour response was obtained in 10 patients (size reduction equal to or greater than 25%), and best response was observed in the first 6 months of treatment in 7 children. Four patients progressed under treatment (all high-grade gliomas) and 2 progressed shortly after stopping the inhibitor (both low-grade gliomas). Five patients had grade 3-4 toxicity, with subsequent full recovery. A good and sustained clinical-radiological response, with acceptable tolerance, is described in patients with BRAF V600E mutated low-grade gliomas treated with BRAF V600E inhibitors. In contrast, the response in patients with high-grade gliomas was intermediate and of short duration, with early tumour progression.
Subject(s)Humans , Child , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Proto-Oncogene Proteins B-raf/genetics , Glioma/genetics , Glioma/drug therapy , Retrospective Studies , Hospitals , Mutation
Tumor heterogeneity is the concept that different tumor cells provide distinct biomorphological lesions, gene expressions, proliferation, microenvironment and graduated capacity of metastatic lesions. Brain tumor heterogeneity has been recently discussed about the interesting interaction of chronic inflammation, microenvironment, epigenetics and glioma steam cells. Brain tumors remain a challenge with regards to medication and disease, due to the lack of treatment options and unsatisfactory results. These results might be the result of the brain tumor heterogeneity and its multiple resistance mechanisms to chemo and radiotherapy.
Subject(s)Neoplastic Stem Cells/cytology , Brain Neoplasms/genetics , Genetic Heterogeneity , Gene Expression Profiling , Glioma/genetics , Receptor Protein-Tyrosine Kinases/genetics , Drug Resistance, Neoplasm/genetics , Stem Cell Niche/genetics , Tumor Microenvironment , Clonal Evolution/genetics , Cellular Microenvironment/genetics , RNA-Seq
Objective The purpose of the present study is to demonstrate the usefulness of intraoperative ultrasound guidance as a technique for the assessment, in real time, of tumor resection and as a navigation aid during intra-axial brain lesion removal on patients admitted in the Neurosurgical Department at the Hospital Universitario de Caracas, Caracas, Venezuela, in 2018. Methods A total of 10 patients were enrolled, each with intra-axial brain lesions with no previous neurosurgical procedures and a mean age of 49 years old, ranging from 29 to 59 years old. Results A male predominance was observed with 7 cases (70%) over 3 female cases (30%). Six patients had lesions in the dominant hemisphere. The frontal lobe was the most commonly affected,with 5 cases, followed by the parietal lobe,with 4 cases. After craniotomy, ultrasound evaluation was performed previously to dural opening, during tumor resection and after tumor removal. The mean tumor size in axial, coronal and sagittal views was 3.72 cm, 3.08 cm and 3.00 cm, respectively, previously to dural opening with intraoperative ultrasound. The average tumor depth was 1.73 cm from the cerebral cortex. The location and removal duration from the beginning of the approach (ultrasound usage time) was 83.60 minutes, and the average surgery duration was 201 minutes. Navigation with intraoperative ultrasound served to resect intra-axial tumors more precisely and safely. There was no postoperative complication associated with the surgery in this series of cases. Conclusions Intraoperative ultrasound guidance for intra-axial subcortical tumor resection is a technique that serves as a surgical and anatomical orientation tool.
Subject(s)Humans , Male , Female , Adult , Middle Aged , Brain Neoplasms/surgery , Monitoring, Intraoperative/methods , Ultrasonography , Neuronavigation/methods , Glioma/surgery , Brain Neoplasms/diagnostic imaging , Epidemiology, Descriptive , Neurosurgical Procedures/methods , Craniotomy/methods , Glioma/physiopathology , Glioma/diagnostic imaging
Resumen Objetivo: Analizar características por resonancia magnética (RM) de gliomas IDH-mutados (grado II y III) en base a parámetros cualitativos, a fin de valorar el rendimiento del signo del mismatch T2-FLAIR y otras características morfológicas de los tumores, en predecir el estado del 1p/19q y su reproducibilidad interobservador. Métodos Estudio retrospectivo, descriptivo y analítico sobre una cohorte de 53 gliomas IDH-mutados (grado II y III) y molecularmente definidos respecto al 1p/19q, seleccionados a partir de la base de datos de la institución, durante el periodo 2014- 2019. Dos neuroradiólogos evaluaron características imagenológicas de forma independiente y enmascarada al diagnóstico: mismatch T2-FLAIR, localización tumoral, bordes, señal, infiltración cortical e inhomogeneidad en T2. Los casos discordantes fueron evaluados por un tercer neuroradiólogo de mayor experiencia. Resultados: Treinta de 53 (56,6%) gliomas fueron no codelecionados, y 23/53 (43,4%) codelecionados. El signo del mismatch T2-FLAIR fue positivo en 16/53 (30,18%) pacientes, 15/16 (93,75%) no codelecionados y 1/16 (6,25%) codelecionado (Exacto de Fisher p = <,0001). Los dos evaluadores demostraron una concordancia interobservador casi perfecta para ese signo, κ =,907 (95% CI, 0,781 a 1,0). La especificidad y el valor predictivo positivo del signo para predecir la ausencia de la codeleción fue de un 95,7% y un 93,8% respectivamente. Discusión: La reciente actualización en la clasificación de los gliomas los clasifica acorde a su perfil molecular. En los últimos años, varios investigadores han estudiado características morfológicas por RM de los tumores con la intención de predecir las características moleculares de los mismos. Conclusión: En nuestra población, el signo del mismatch T2-FLAIR es el único biomarcador radiológico que muestra asociación estadísticamente significativa en predecir la ausencia de codeleción en los gliomas IDH-mutados (grado II y III), con una alta especificidad y un alto valor predictivo positivo.
Abstract Objective: To analyze magnetic resonance (MR) characteristics of IDH-mutated gliomas (grades II/III) utilizing qualitative parameters with the goal of assessing the performance of the T2-FLAIR mismatch sign and other morphological characteristics of tumors in predicting the 1p/19q co-deletion status as well as inter-observer reproducibility. Methods: Retrospective and descriptive study analyzing a cohort of 53 IDH-mutated lower-grade (grades II/III) gliomas with known 1p/19q co-deletion status. Patients meeting selection criteria for this study were taken from our institutional data from 2014-2019. Two neuroradiologists assessed the following imaging characteristics independently, and blinded from the diagnosis: T2-FLAIR mismatch, tumor location, borders, signal characteristics, cortical infiltration and T2* inhomogeneity. In the event of discordant interpretations, a third senior neuroradiologist also evaluated the case. Results: 23 of the 53 (43.4%) gliomas demonstrated 1p/19q co-deletion and 30 of 53 (56.6%) did not. T2-FLAIR mismatch was positive in 16 of 53 cases (30.2%) with 15 of 16 (93.8%) demonstrating no co-deletion and 1/16 (6.25%) with co-deletion (Fisher's exact p = < .0001). The two readers showed an almost perfect interreader agreement for this sign κ = 0.907 (95% CI, 0.781 to 1.0). Specificity and positive predictive value of the sign to predict the absence of co-deletion was 95.7% and 93.8% respectively. Discussion: The recent update in classification of lower-grade gliomas segregates gliomas according to molecular profile. In the recent past, many researchers have studied MR morphologic characteristics of these tumors with the intention of predicting molecular features of said tumors Conclusion: In our patient population, T2-FLAIR mismatch sign is the only radiologic biomarker that shows statistically significant association with the absence of 1p/19q co-deletion in lower-grade gliomas, with high specificity and positive predictive value.
Subject(s)Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Brain Neoplasms/diagnostic imaging , Biomarkers , Glioma/diagnostic imaging , Oligodendroglioma/diagnostic imaging , Astrocytoma/diagnostic imaging , Magnetic Resonance Spectroscopy , Epidemiology, Descriptive , Retrospective Studies , Glioma/classification
ABSTRACT The anesthesia for awake craniotomy (AC) is a consecrated anesthetic technique that has been perfected over the years. Initially used to map epileptic foci, it later became the standard technique for the removal of glial neoplasms in eloquent brain areas. We present an AC anesthesia technique consisting of three primordial times, called awake-asleep-awake, and their respective particularities, as well as delve into the anesthetic medications used. Its use in patients with low and high-grade gliomas was favorable for the resection of tumors within the functional boundaries of patients, with shorter hospital stay and lower direct costs. The present study aims to systematize the technique based on the experience of the largest philanthropic hospital in Latin America and discusses the most relevant aspects that have consolidated this technique as the most appropriate in the surgery of gliomas in eloquent areas.
RESUMO A anestesia para craniotomia em paciente acordado (CPA ou awake craniotomy) é técnica anestésica consagrada e aperfeiçoada ao longo dos últimos anos. Utilizada inicialmente para mapeamento de focos epilépticos, consolidou-se posteriormente como técnica padrão para a remoção de neoplasias de origem glial em áreas eloquentes cerebrais. A técnica de anestesia CPA apresentada constitui-se em três tempos primordiais denominados acordado-dormindo-acordado (asleep-awake-asleep) e respectivas particularidades, assim como o manejo quanto às medicações anestésicas utilizadas de forma pormenorizada. A utilização em gliomas de baixo e de alto grau se demonstrou favorável para a ressecção de tumores dentro dos limites funcionais dos pacientes, com menor tempo de internação hospitalar e de custos diretos. O presente estudo visa realizar a sistematização da técnica baseada na experiência do maior Hospital Filantrópico da América Latina e discute os aspectos mais relevantes que consolidaram essa técnica como a mais adequada na cirurgia dos gliomas em áreas eloquentes.
Subject(s)Humans , Brain Neoplasms/surgery , Glioma/surgery , Anesthesia , Wakefulness , Craniotomy
Introdução: Os gliomas representam 80% dos tumores do sistema nervoso central. A Organização Mundial da Saúde (OMS) adicionou, em 2016, critérios moleculares na classificação dos gliomas. A fisiopatologia e os fatores de risco desses tumores ainda não são totalmente conhecidos. Objetivo: Realizar uma análise retrospectiva dos laudos anatomopatológicos e imuno-histoquímicos de gliomas. Método: Estudo transversal, retrospectivo e descritivo, a partir de exames anatomopatológicos e imuno-histoquímicos realizados entre janeiro de 2014 e dezembro de 2018 em um laboratório de anatomia patológica na cidade de Maringá-PR. Dos 234 laudos relacionados com o termo glioma, 204 foram selecionados para este estudo. Resultados: Foram encontrados tumores astrocitários, ependimários e oligodendrogliais, sendo que os astrocitomas corresponderam à maioria (86,8% dos casos encontrados). A média de idade ao diagnóstico foi de 51,8 anos e houve maior prevalência desses tumores no sexo masculino. Também foram analisadas mutações detectáveis por imuno-histoquímica como p53 (mutada em 66,7% dos testados), isocitrato desidrogenase (IDH) (28,6% mutados), X-linked alpha-thalassemia mental retardation (ATRX) (21,0%) e marcadores diagnósticos como o epithelial membrane antigen (EMA) positivo em todos os ependimomas analisados. Conclusão: É inegável a necessidade de novas pesquisas sobre os gliomas tanto no campo epidemiológico, tendo em vista a nova classificação, quanto no escopo fisiopatológico e clínico, com o objetivo de melhorar o entendimento sobre a patologia e o tratamento dos pacientes
Introduction: Gliomas represent 80% of the central nervous system tumors. World Health Organization (WHO) has added, in 2016, molecular features to the classification of gliomas. The pathophysiology and risk factors of these tumors are not yet fully understood. Objective: Perform a retrospective analysis of immunohistochemical and anatomopathological reports of gliomas. Method: Cross-sectional, retrospective and descriptive study carried out from anatomopathological and immunohistochemical exams made between January 2014 and December 2018 in a pathological anatomy laboratory in the city of Maringá-PR. Of the 234 reports related to the term glioma, 204 were selected for this study. Results: Astrocytic, ependymal and oligodendroglial tumors were found, with astrocytomas accounting for the majority (86.8% of the cases found). Mean age at diagnosis was 51.8 years and the prevalence was higher in men. Furthermore, immunohistochemically detectable mutations were analyzed, such as p53 (mutated in 66.7% of those tested), isocitrate dehydrogenase (IDH) (28.6% mutated), X-linked alpha-thalassemia mental retardation (ATRX) (21.0%) and diagnostic markers such as positive epithelial membrane antigen (EMA) in all analyzed ependymomas. Conclusion: The necessity of further researches on gliomas is undeniable , both epidemiologically considering the new classification and within the clinical and pathophysiological scope in order to improve the understanding of the pathology and the treatment for the patients
Introducción: Los gliomas representan 80% de los tumores del sistema nervioso central. La Organización Mundial de la Salud (OMS) agregó, en 2016, criterios moleculares sobre como clasificar los gliomas. La fisiopatología y los factores de riesgo de estos tumores aún no se comprenden completamente. Objetivo: Realizar un análisis retrospectivo de informes inmunohistoquímicos y anatomopatológicos de gliomas. Método: Estudio transversal, retrospectivo y descriptivo con base em pruebas anatomopatológicas e inmunohistoquímicas realizadas entre enero de 2014 y diciembre de 2018 en un laboratorio de anatomía patológica de la ciudad de Maringá-PR. De los 234 informes relacionados con el término glioma, se seleccionaron 204 para este estudio. Resultados: Se encontraron tumores astrocíticos, ependimarios y oligodendrogliales, siendo los astrocitomas la mayoría (86,8% de los casos encontrados). La edad media al diagnóstico fue de 51,8 años y hubo una mayor prevalencia de estos tumores en el sexo masculino. También se analizaron mutaciones detectables inmunohistoquímicamente, como p53 (mutado en 66,7% de los analizados), isocitrato desidrogenase(IDH) (28,6% mutado), X-linked alpha-thalassemia mental retardation (ATRX) (21,0%) y marcadores de diagnóstico como epithelial membrane antigen (EMA) positivo en todos los ependimomas analizados. Conclusión: Es innegable la necesidad de profundizaren las investigaciones sobre los gliomas, tanto en el campo epidemiológico, ante la nueva clasificación, como en el ámbito fisiopatológico y clínico, con el objetivo de mejorar el conocimiento sobre la patología y el tratamiento de los pacientes
Subject(s)Humans , Male , Female , Astrocytoma , Immunohistochemistry , Molecular Epidemiology , Glioblastoma , Glioma , Glioma/classification , Glioma/immunology
Vasculogenic mimicry (VM) plays an important role in human glioma progression and resistance to antiangiogenic therapy as a compensatory neovascularization mechanism in malignant tumors. Caveolin-1 (Cav-1) has been found to contribute to VM formation. However, it remains largely unknown whether Cav-1 expression correlates with VM in glioma. In this study, we examined CAV-1 expression levels and VM in human glioma cell lines and in 94 human gliomas with different grades of malignancy, and present Cox proportional hazards regression. The molecular role of Cav-1 in glioma cells was investigated using quantitative polymerase chain reaction (qRT-PCR) assays, western blotting, CCK-8 assays, and tubule formation assays. Cav-1 expression and VM formation were positively correlated with each other and both were closely associated with glioma development and progression as evidenced by the presence of cystic tumor, shortened survival time, and advanced-stage glioma in glioma patients with Cav-1 overexpression/increased VM formation. Cav-1 promoted U251 glioma cell proliferation and VM formation in a Matrigel-based 3D culture model. VM-associated factors including hypoxia-inducible factor 1α (HIF-1α) and p-Akt was significantly elevated by Cav-1 overexpression but suppressed by siCav-1 in U251 cells. Collectively, our study identified Cav-1 as an important regulator of glioma cell proliferation and VM formation, contributing to glioma development and progression.