Central nervous system (CNS) malignant neoplasms may lead to venous thromboembolism (VTE) and bleeding, which result in rehospitalization, morbidity and mortality. We aimed to assess the incidence of ...VTE and bleeding in this population. Methods: This systematic review and meta-analysis (PROSPERO CRD42023423949) were based on a standardized search of PubMed, Virtual Health Library and Cochrane (n = 1653) in July 2023. After duplicate removal, data screening and collection were conducted by independent reviewers. The combined rates and 95% confidence intervals for the incidence of VTE and bleeding were calculated using the random effects model with double arcsine transformation. Subgroup analyses were performed based on sex, age, income, and type of tumor. Heterogeneity was calculated using Cochran's Q test and I.sup.2 statistics. Egger's test and funnel graphs were used to assess publication bias. Results: Only 36 studies were included, mainly retrospective cohorts (n = 30, 83.3%) from North America (n = 20). Most studies included were published in high-income countries. The sample size of studies varied between 34 and 21,384 adult patients, mostly based on gliomas (n = 30,045). For overall malignant primary CNS neoplasm, the pooled incidence was 13.68% (95%CI 9.79; 18.79) and 11.60% (95%CI 6.16; 18.41) for VTE and bleeding, respectively. The subgroup with elderly people aged 60 or over had the highest incidence of VTE (32.27% - 95%CI 14.40;53.31). The studies presented few biases, being mostly high quality. Despite some variability among the studies, we observed consistent results by performing sensitivity analysis, which highlight the robustness of our findings. Conclusions: Our study showed variability in the pooled incidence for both overall events and subgroup analyses. It was highlighted that individuals over 60 years old or diagnosed with GBM had a higher pooled incidence of VTE among those with overall CNS malignancies. It is important to note that the results of this meta-analysis refer mainly to studies carried out in high-income countries. This highlights the need for additional research in Latin America, and low- and middle-income countries.
Despite the advances in glioblastoma (GBM) treatment, the average life span of patients is 14 months. Therefore, it is urgent to identity biomarkers of prognosis, treatment response, or development ...of novel treatment strategies. We previously described the association of high epidermal growth factor-like domain multiple 7 (EGFL7) expression and unfavorable outcome of pilocytic astrocytoma patients. The present study aims to analyze the prognostic potential of EGFL7 in GBM isocitrate dehydrogenase (IDH)-wildtype, using immunohistochemistry and in silico approaches.
Spearman's correlation analysis of The Cancer Genome Atlas RNA sequencing data was performed. The genes strongly correlated to EGFL7 expression were submitted to enrichment gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Additionally, EGFL7 expression was associated with patient overall survival. The expression of EGFL7 was analyzed through immunohistochemistry in 74 GBM IDH-wildtype patients' samples, and was associated with clinicopathological data and overall survival.
In silico analysis found 78 genes strongly correlated to EGFL7 expression. These genes were enriched in 40 biological processes and eight KEGG pathways, including angiogenesis/vasculogenesis, cell adhesion, and phosphoinositide 3-kinase-Akt, Notch, and Rap1 signaling pathways. The immunostaining showed high EGFL7 expression in 39 cases (52.7%). High immunolabelling was significantly associated with low Karnofsky Performance Status and poor overall survival. Cox analysis showed that GBMs IDH-wildtype with high EGFL7 expression presented a higher risk of death compared to low expression (hazard ratio, 1.645; 95% confidence interval, 1.021 to 2.650; p = .041).
This study gives insights regarding the genes that are correlated with EGFL7, as well as biological processes and signaling pathways, which should be further investigated in order to elucidate their role in glioblastoma biology.
Rosette-forming glioneuronal tumor (RGNT) of the IV ventricle is a rare and recently recognized brain tumor entity. It is histologically composed by two distinct features: a glial component, ...resembling pilocytic astrocytoma, and a component forming neurocytic rosettes and/or perivascular rosettes. Herein, we describe a 33-year-old man with RGNT arising in the spinal cord. Following an immunohistochemistry validation, we further performed an extensive genomic analysis, using array-CGH (aCGH), whole exome and cancer-related hotspot sequencing, in order to better understand its underlying biology. We observed the loss of 1p and gain of 1q, as well as gain of the whole chromosomes 7, 9 and 16. Local amplifications in 9q34.2 and 19p13.3 (encompassing the gene SBNO2) were identified. Moreover, we observed focal gains/losses in several chromosomes. Additionally, on chromosome 7, we identified the presence of the KIAA1549:BRAF gene fusion, which was further validated by RT-PCR and FISH. Across all mutational analyses, we detected and validated the somatic mutations of the genes MLL2, CNNM3, PCDHGC4 and SCN1A. Our comprehensive molecular profiling of this RGNT suggests that MAPK pathway and methylome changes, driven by KIAA1549:BRAF fusion and MLL2 mutation, respectively, could be associated with the development of this rare tumor entity.
Glioblastoma (GBM), the most frequent and aggressive brain tumor, is characterized by marked angiogenesis directly related to invasiveness and poor prognosis. Hypoxia is considered to be an important ...stimulus for angiogenesis by inducing hypoxia‐inducible factor 1‐alpha (HIF‐1α) overexpression that activates platelet‐derived growth factor (PDGF) and VEGF. The aim of this study is to analyze the expression of PDGF‐C, VEGF in endothelial and tumor cells of GBM and their relation to HIF‐1α expression. Two hundred and eight GBM cases were studied by tissue microarray immunohistochemical preparation. Expression of HIF‐1α, VEGF and PDGF‐C was observed in 184 (88.5%), 131 (63%) and 160 (76.9%) tumor cases, respectively. The numbers of vessels were quantified by CD34, PDGF‐C, VEGF and CD105 staining, and were in median 20, 16, 5 and 6, respectively. The GBMs that showed positive or negative expression for HIF‐1α showed a median vascular density of 30 and 14, respectively, for CD34 (P < 0.015). Positive expression for HIF‐1α was correlated with VEGF and PDGF‐C expression in tumors (P < 0.001). There was a significant correlation between VEGF and PDGF‐C expression in the cytoplasm of GBM tumor cells (P < 0.0001). We showed that VEGF expression in tumor cells was correlated with its expression in blood vessels (P < 0.0001). Endothelial cells with PDGF‐C and VEGF positive expression were also positive for CD105 and their nuclei for Ki‐67, confirming the neoangiogenic and proliferative influence of VEGF and PDGF‐C. VEGF nuclear staining in tumor cells (P = 0.002) as well as nuclear staining for HIF‐1α and VEGF (P = 0.005) correlated with survival. In summary, our present findings of the concomitant upregulation of PDGF‐C with VEGF in GBM tumor cells and vessels further reinforce the benefit of using combined anti‐angiogenic approaches to potentially improve the therapeutic response for GBM.
Copy number alterations (CNA) are one of the driving mechanisms of glioma tumorigenesis, and are currently used as important biomarkers in the routine setting. Therefore, we performed CNA profiling ...of 65 astrocytomas of distinct malignant grades (WHO grade I-IV) of Brazilian origin, using array-CGH and microsatellite instability analysis (MSI), and investigated their correlation with TERT and IDH1 mutational status and clinico-pathological features. Furthermore, in silico analysis using the Oncomine database was performed to validate our findings and extend the findings to gene expression level. We found that the number of genomic alterations increases in accordance with glioma grade. In glioblastomas (GBM), the most common alterations were gene amplifications (PDGFRA, KIT, KDR, EGFR, and MET) and deletions (CDKN2A and PTEN) Log-rank analysis correlated EGFR amplification and/or chr7 gain with better survival of the patients. MSI was observed in 11% of GBMs. A total of 69% of GBMs presented TERT mutation, whereas IDH1 mutation was most frequent in diffuse (85.7%) and anaplastic (100%) astrocytomas. The combination of 1p19q deletion and TERT and IDH1 mutational status separated tumor groups that showed distinct age of diagnosis and outcome. In silico validation pointed to less explored genes that may be worthy of future investigation, such as CDK2, DMRTA1, and MTAP Herein, using an extensive integrated analysis, we indicated potentially important genes, not extensively studied in gliomas, that could be further explored to assess their biological and clinical impact in astrocytomas.
INTRODUCTION:
Meningiomas are the most common intracranial tumors, accounting for 36% of cases. The World Health Organization (WHO) classifies these tumors into three histological grades: benign ...(grade I), atypical (grade II) and anaplastic (grade III). Although most lesions are benign, the treatment that is currently widely recommended is restricted to surgery and/or radiotherapy, which are often insufficient for aggressive lesions or lesions that involve neurovascular structures, making the treatment of meningiomas a challenge even today. The understanding of molecular changes in meningiomas may contribute to the identification of aggressiveness markers and possible new therapeutic targets.
METHODS:
The expressions of approximately 800 genes were evaluated, using the PanCancer Nanostring Kit, in 17 meningiomas (6 benign, 6 atypical and 5 anaplastic) and 6 control arachnoids. Comparisons of gene expression between samples of different histological grades and between tumor and control arachnoid samples were performed and the results tabulated in heatmaps after analysis by bioinformatics tools (NSolver, R Statistics, and DAVID, ROSALIND and COSMIC online databases).
RESULTS:
The molecular cell cycle pathway has components upregulated in the three grades of meningiomas analyzed and significantly induced in histologically more aggressive meningiomas. Hyper-regulated genes may be candidates for markers of aggression. In addition, cell cycle induction can be a therapeutic target in more aggressive meningiomas, with the introduction of cell cycle blocking drugs.
CONCLUSIONS:
The hyper-regulated cell cycle pathway may be associated with aggressiveness in meningiomas. Cell cycle induction in meningiomas can be a therapeutic target for the treatment of these tumors, through cell cycle blockers. Additional studies are needed to corroborate the findings of this study.
Trigone ventricular meningiomas: surgical approaches Zanini, Marco Antonio; Faleiros, Antonio Tadeu Souza; Almeida, Carlos Roberto ...
Arquivos de neuro-psiquiatria,
08/2011, Volume:
69, Issue:
4
Journal Article
Peer reviewed
Open access
Report our experience with trigone ventricular meningiomas and review the surgical approaches to the trigone.
From 1989 to 2006, six patients with meningiomas of the trigone of the lateral ventricles ...underwent microsurgical resection. Their clinical features, image, follow up, and surgical approaches were retrospectively analyzed.
Five patients presented with large and one with small volume meningioma. Unspecific symptoms occurred in three patients; intracranial hypertension detected in three patients; homonymous hemianopsy in three; and motor deficit present in one patient. Three patients were operated by transparietal transcortical approach, two by middle temporal gyrus approach, and one by parieto-occipital interhemispheric precuneus approach. Total resection was achieved in all patients without additional deficits.
Judicious preoperative plan, adequate knowledge of anatomy, and use of correct microsurgical techniques are fundamental in achieving complete resection of trigone meningioma with low morbidity.
NUT-CARCINOMA INVOLVING TRIGEMINAL NERVE - A CASE REPORT CORACIN, Fabio Luiz; Neto, Victor Tieghi; Teixeira, Gustavo Ramos ...
Oral surgery, oral medicine, oral pathology and oral radiology,
July 2023, 2023-07-00, Volume:
136, Issue:
1
Journal Article
Peer reviewed
NUT-carcinoma is a rare aggressive disease caused by BRD4/3‐NUT fusion that results in MYC upregulation. A 50-years-old male patient presented frontotemporal headache and paraesthesia, evolving with ...worsening headache, diplopia, ptosis and reduced visual acuity for at least 12 months. Clinical diagnosis was meningioma due to an expansive process in the right temporal fossa with hyperostosis and optic canal stenosis. Histological analysis revealed malignant neoplasm presenting cohesive blocks of basaloid cells with foci of abrupt keratinization and necrosis, with infiltration of dense connective tissue and bone marrow. Immunohistochemistry was positive for EMA, P63, INI1(retained), AE1/AE3, CK5/6, CK8-18, CD117 and NUT. In addition, Ki-67 was positive in 80% of the neoplasia. Therefore, the final diagnosis was NUT carcinoma. The patient is still alive at the last follow-up. This case highlights the importance of considering NUT-carcinoma in the provisional diagnosis for undifferentiated or poorly differentiated neoplasms and immunohistochemistry can aid diagnosis.
IDH1 mutations in a Brazilian series of Glioblastoma Uno, Miyuki; Oba-Shinjo, Sueli Mieko; da Silva, Roseli ...
Clinics (São Paulo, Brazil),
January 2011, 2011-00-00, 2011-01-00, 20110101, 2011-01-01, Volume:
66, Issue:
1
Journal Article
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