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Background: Ependymomas (EPNs) of the spinal region are a heterogeneous group of tumors that account for 17.6 % in adults. Four types have been recognized: subependymoma, spinal ependymoma (Sp-EPN), myxopapillary ependymoma (MPE), and Sp-EPN-MYCN amplified, each with distinct histopathological and molecular features., Methods: This study investigated the clinical and pathological characteristics and MYCN expression levels of 35 Sp-EPN and MPE cases diagnosed at a tertiary university hospital over a decade-long period., Results: Twenty-five cases were Sp-EPN and 10 cases were MPE, and were graded as WHO grade 2, except for 1 Sp-EPN case with grade 3 features. The most common symptoms were lower back pain and difficulty in walking. Radiology showed different tumor sizes and locations along the spinal cord, with MPEs exclusively in the lumbosacral region. Surgery was the main treatment, and gross total resection was achieved in all cases except for one. Immunohistochemistry showed low Ki-67 proliferation indices in all cases, and no MYCN expression. During follow-up, 3 (8.6 %) cases recurred and/or metastasized and 5 cases (14.3 %) died. No significant difference was found in disease-free survival or overall survival between Sp-EPN and MPE cases. However, 3 cases with grade 2 histology demonstrated recurrence and/or metastasis, despite the lack of MYCN expression., Conclusion: Our results underscore the multifactorial nature of tumor aggressiveness in EPNs of the spinal region. This study enhances our knowledge of the clinical and pathological features of Sp-EPNs and MPEs and highlights the need for better diagnostic and prognostic markers in these rare tumors., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Spinal cord glioma (SCG), a rare subset of central nervous system (CNS) glioma, represents a complex challenge in neuro-oncology. There has been research showing that Retinol Dehydrogenase 10 (RDH10) may be a tumor promoting factor in brain glioma, but the biological effects of RDH10 remain undefined in SCG. Methods: We performed gene set enrichment analysis (GSEA) and unsupervised clustering analysis to investigate the roles of EMT (epithelial-mesenchymal transition) in glioma. DEG (differently expressed gene) screening and correlation analysis were conducted to filter the candidate genes which were closely associated with EMT process in SCG. Enrichment analysis and GSVA (Gene Set Variation Analysis) were conducted to investigate the potential mechanism of RDH10 for SCG. Trans-well and healing assay were performed to explore the role of RDH10 in the invasion of SCG. Western blotting was performed to evaluate the levels of markers in PI3K-AKT and EMT pathway. In vivo tests were conducted to verify the role of RDH10 in EMT process. Results: Bioinformatic analysis demonstrated the EMT pathway was associated with dismal prognosis of glioma. Further analysis demonstrated that RDH10 showed the strongest correlation with the EMT process. Retinol Dehydrogenase 10 expression was significantly increased in SCG tissues, correlating with advanced tumor grade and unfavorable prognosis. Functional analysis indicated that decreasing RDH10 levels impeded the invasive and migratory abilities of SCG cells, whereas increasing RDH10 levels augmented them. Enrichment analysis and western blot revealed that RDH10 regulated EMT process of SCG by PI3K-AKT pathway. We observed that the enhanced invasion ability and increased EMT-related protein induced by RDH10 overexpression can be suppressed by PI3K-AKT pathway inhibitor (LY294002). Conclusion: Our research found that RDH10 was an effective biomarker associated with tumor grade and prognosis of SCG. RDH10 could regulate EMT process of SCG through PI3K-AKT pathway., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Long noncoding RNA (LncRNA) TPT1-AS1 is an oncogene in ovarian cancer and cervical cancer, while its role in glioblastoma (GBM) is unknown. The bioinformatics analysis in this study showed that miR-23a-5p may bind to TPT1-AS1. This study was performed to investigate the interactions between miR-23a-5p and TPT1-AS1 in GBM. Materials and Methods: A total of 60 GBM patients (40 males and 20 females, 24 to 60 years old, mean age 41.7 ± 7.8 years old) were enrolled at the First Hospital of Jilin University between April 2016 and April 2018. Gene expression levels were determined by qPCR and Western blot. Cell transfections were performed to analyze the interactions between TPT1-AS1, miR-23a-5p, and extracellular matrix protein 1 (ECM1). Cell proliferation was detected by cell proliferation assay. Results: The authors found miR-23a-5p was downregulated in GBM and TPT1-AS1 was upregulated in GBM, whereas the expression of these two was not significantly correlated. In GBM cells, overexpression of TPT1-AS1 did not affect the expression of miR-23a-5p, but upregulated ECM1. In cell proliferation assay, overexpression of TPT1-AS1 and ECM1 resulted in increased proliferation rate of GBM cells. Overexpression of miR-23a-5p attenuated the effects of overexpressing TPT1-AS1. Conclusions: TPT1-AS1 may sponge miR-23a-5p in GBM to promote cancer cell proliferation by upregulating ECM1.

Few cases of malignant transformation of supposedly low-grade gliomas were described in patients with neurofibromatosis type 1 (NF1). A 27-year-old man with NF1 presented with weakness of his lower extremities and was radiologically found to have a spinal intramedullary tumor primarily involving the Th11 level. The tumor histologically demonstrated features diagnosed as a low-grade astrocytoma, subtype indeterminate (WHO grade II). Immunohistochemically, GFAP was positive, and IDH1 R132H and BRAF V600E were negative. ATRX immunoreactivity was retained. Five years after the surgery, the intramedullary tumor extended to the levels from Th8 to L1 and was partially resected. It showed histologic features similar to those of the first tumor. Two years after the second surgery, the residual spinal cord tumor was found to widely involve the levels from Th5 to L3. Spinal cordectomy was subsequently undertaken and revealed anaplastic glial cells infiltrating diffusely into the spinal cord parenchyma, with prominent subarachnoid spreading and nerve root involvement. Both necrosis and microvascular proliferation were observed. This recurrent tumor was histologically indistinguishable from glioblastoma. Loss of ATRX was noted in the second and third surgical specimens. This is the first histologically proven case of malignant transformation of NF1-associated astrocytoma with ATRX loss during the course.

The objectives of this study were to explore the possible mechanisms of pediatric ependymoma using bioinformatics methods and provide potential genes and signaling pathways for pediatric ependymoma study. The data of GES74195 from Gene Expression Ominibus was analyzed by R language for pediatric ependymoma study. The differentially expressed genes were explored using gene set enrichment analysis, search tool for the retrieval of interacting genes, Cytoscape as well as other mainstream bioinformatics methods. Extracellular matrix-receptors interaction pathways and focal adhesion pathway were demonstrated as the key signaling pathway for pediatric ependymoma. The potential hub genes enriched in the two signaling pathways were regarded as final hub genes for this microarray analysis. The development and progression of pediatric ependymoma were associated with epithelial-mesenchymal-transition. Various potential hub genes and potential key signaling pathways in order to further explore their values in the diagnosis and treatment of this disease in the future., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We aim to elucidate the clinical characteristics of patients with primary spinal cord glioblastoma (PSC GBM) and prognostic factors for their outcomes., Methods: A cohort of 11 patients with pathologically diagnosed PSC GBM from our center were retrospectively reviewed. The clinical, radiologic, operative, and molecular information were recorded, and univariate analysis was performed to identify prognostic factors., Results: The patient cohort included 5 males (45.5%) and 6 females (54.5%) with a median age of 26 years (range, 9-69 years). The median duration of the preoperative symptoms was 4.0 months (range, 0.5-120 months). Subtotal resection was achieved in 8 patients (72.7%) and partial resection in 3 (27.3%). Two patients (18.2%) underwent postoperative adjuvant chemoradiotherapy, 2 patients underwent (27.3%) chemotherapy only, and 6 patients (54.5%) neither. Two patients underwent additional therapy with bevacizumab. After a mean follow-up of 12.4 months (range, 1-33 months), Kaplan-Meier plot showed that the median progression-free survival and overall survival were 6.0 (range, 0.5-12.0) months and 12.0 (range, 1.0-33.0) months, respectively, and 1-year survival was 31.8%. Age at diagnosis and duration of the preoperative symptoms were confirmed as prognostic factors of progression-free survival and overall survival in univariate analysis (P < 0.05)., Conclusions: Despite aggressive treatment, PSC GBM still has a dismal prognosis and leads to severe neurologic deficit. Age at diagnosis and duration of the preoperative symptoms were confirmed as prognostic factors, yet the role of adjuvant radiochemotherapy and extent of resection are still unclear, necessitating further research., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Lumbosacral lipomas (LSLs), one form of closed spinal dysraphism, are congenital disorders of the terminal spinal cord (SC). Delayed neurologic deterioration often occurs in the subsequent developmental course of the patient. Identifying the cellular and molecular factors underlying the progressive damage to neural structures is a prerequisite for developing treatment strategies for LSLs., Methods: Nine LSL specimens obtained from the SC/lipoma interface during surgical resection were examined. Normal SC tissue served as a control. Clinical characteristics were obtained, and spinal magnetic resonance imaging was re-evaluated. Cellular marker profiles were established. Immunoreactivity (IR) of hypoxia-inducible factor 1α (HIF-1α/-2α), erythropoietin (Epo)/erythropoietin receptor (EpoR), interleukin-1β (IL-1β)/IL-1R1, and tumor necrosis factor α/tumor necrosis factor receptor type 1 were analyzed qualitatively and semiquantitatively by densitometry. Colabeling with cellular markers was determined by multifluorescence labeling. Cytokines were further analyzed by real-time reverse transcription polymerase chain reaction., Results: LSL specimens showed significant gliosis. HIF-1α/HIF-2α-IR and Epo/Epo-IR were found at significantly higher levels in the LSL specimens, as were IL-1β-/IL-1β receptor type 1 (IL1-R1) and tumor necrosis factor α/tumor necrosis factor receptor type 1 (P < 0.001), than were the controls. At the messenger RNA level, cytokines appeared partially induced. Double immunofluorescence labeling confirmed the costaining of these factors with inflammatory and glial markers., Conclusions: The expression of hypoxia-related and inflammatory mediators was shown for the first time in LSL specimens. These factors might play a role in multifactorial secondary lesion cascades underlying further damage to the neural placode in closed dysraphism., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To investigate the expression of H3K27me3 in different anatomical sites and analyze its prognostic value in children with ependymoma., Methods: A total of 188 children diagnosed with ependymoma were admitted to the Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, between 2012 and 2017, and regular follow-up was conducted. Expression of H3K27me3 was analyzed by immunohistochemistry and scored semiquantitatively. The prognostic correlation was analyzed by Kaplan-Meier and Cox regression survival analyses., Results: Of the 188 children with ependymoma, 61.7% were male, and the median and average age was five years (0-17 years) and 6.26 years, respectively. There were 65 cases of supratentorial ependymoma, 115 cases of infratentorial ependymoma, and 8 cases of spinal cord ependymoma. The median follow-up time was 39.95 months (0.3-90.19 months). Five-year progression-free survival (PFS) and overall survival (OS) were 48.5% and 61.4%, respectively. Kaplan-Meier univariate survival analysis showed that H3K27me3 expression had significant effects on PFS (P = 0.0003) and OS (P < 0.0001) in infratentorial ependymoma, but only affected OS (P = 0.03) in supratentorial ependymoma., Conclusion: In Chinese children, infratentorial ependymoma with incomplete resection and no adjuvant radiotherapy is associated with poor OS. On the other hand, low expression of H3K27me3 indicates poor prognosis of infratentorial ependymoma, but it has no significant prognostic value for supratentorial ependymoma. In addition, high expression of H3K27me3 in spinal ependymoma may indicate a better prognosis., (© 2019 Wiley Periodicals, Inc.)

Intramedullary spinal cord tumors (IMSCT) are rare entities for which there currently exist no standardized treatment paradigms. Consequently, patients usually receive treatment modalities that were established for intracerebral tumors; these approaches, however, typically result in functional impairment, recurrent tumor growth, and short overall survival. There is a distinct lack of promising research efforts in this field, which raises questions about whether spinal cord tumor microenvironment (TME) might promote the development, progression, and treatment resistance of IMSCT. In this review, we aim to examine spinal cord biology, compare spinal cord and brain microenvironments, and discuss mutual interactions between IMSCT and TME. Manipulating these pathways may provide new treatment approaches for future patient groups.

Diffuse midline gliomas (DMGs) are rare and devastating tumors with limited therapeutic options. Programmed death-ligand 1 (PD-L1) expression represents a potential predictive biomarker for immunotherapy. One hundred and twenty-six DMGs (89 adult and 37 pediatric) were assessed for immune profile (PD-L1, cluster of differentiation (CD3, CD8) and genetic markers (mutation in 27th amino acid of histone H3 (H3K27M), alpha thalassemia/mental retardation syndrome X-linked (ATRX), isocitrate dehydrogenase 1 (IDH1), p53) by immunohistochemistry. Sanger sequencing was done for IDH1 and H3K27M. The thalamus was the commonest site. Four molecular subgroups of DMGs were identified. H3K27M mutation was more frequent in children (P = 0.0001). The difference in median overall survival (OS) was not significant in any of the four molecular subgroups (P > 0.05). PD-L1 expression was significantly higher in H3K27M/IDH1 double-negative adult glioblastomas (GBMs) (P = 0.002). Strong PD-L1 expression was more frequent in grade IV tumors and thalamic location, although the difference was not significant (P = 0.14 and P = 0.19 respectively). Positive PD-L1 expression was significantly associated with high tumor-infiltrating lymphocytes count (P < 0.05). There was no significant difference in median OS in PD-L1-positive versus negative cases among four genetic subgroups (P > 0.05). On univariate analysis, there was no direct correlation of PD-L1 with any genetic alteration, except H3K27M mutation (P = 0.01). CD3 infiltration was similar in both adults and pediatric ages (84.3% and 78.4%, respectively) while CD8 expression was significantly greater in adults compared to children (74.1% vs 37.8%, P = 0.0001). This is the first comprehensive analysis highlighting molecular and immune profiles of DMGs. Despite molecular and clinicopathological diversity, overall survival in DMGs remains dismal. Multicentric studies with larger numbers of cases should be undertaken for stratifying DMGs according to their age, immune and molecular profiles, to develop effective immunotherapies., (© 2019 Japanese Society of Neuropathology.)

This study is aimed to clarify the potential role of lncRNA LINC00899 in invasion and migration of spinal ependymoma cells through the FoxO pathway via RBL2. Spinal ependymoma related chip data (GSE50161 and GSE66354) was initially downloaded and differentially expressed lncRNAs were screened out. Fifty-eight cases of spinal ependymoma and normal ependymal tissues were collected. The effects of LINC00899 and RBL2 on the spinal ependymoma cell migration and invasion were determined using the third generation spinal ependymoma cells and transfection with LINC00899 vector, siRNA-LINC00899 and siRNA-RBL2. The expression of LINC00899, pathway and cell proliferation- and apoptosis-related factors was determined. Finally, we also detected cell proliferation, migration, invasion, cycle and apoptosis after transfection. Our results showed that LINC00899 was up-regulated in spinal ependymoma and RBL2 was confirmed as a target gene of LINC00899 and found to be involved in regulation of FoxO pathway. LINC00899 expression increased in spinal ependymoma tissues whereas RBL2 expression decreased. Moreover, we found that siRNA-LINC00899 could elevate RBL2, p21, p27 and Bax levels, decrease FoxO, Bcl-2, Vimentin, Annexin levels, reduced cell proliferation, migration and invasion and enhanced apoptosis. Taken together, our study suggests that down-regulated LINC00899 exerts anti-oncogenic effects on spinal ependymoma via RBL2-dependent FoxO, which provides a novel therapeutic target for the treatment of spinal ependymomas.

Primary high-grade infiltrating gliomas of the spinal cord are rare, with prior series including limited numbers of cases and reporting poor outcomes. Additionally, the molecular profile of high-grade infiltrating gliomas of the spinal cord has not been well characterized. We identified 13 adult patients whose surgery had been performed at our institution over a 26-year-period. Radiologically, nine cases harbored regions of post-contrast enhancement. Existing slides were reviewed, and when sufficient tissue was available, immunohistochemical stains (IDH1-R132H, H3-K27M, H3K27-me3, ATRX, p53 and BRAF-V600E), and a targeted 150-gene neuro-oncology next-generation sequencing panel were performed. The 13 patients included 11 men and 2 women with a median age of 38 years (range = 18-69). Histologically, all were consistent with an infiltrating astrocytoma corresponding to 2016 WHO grades III (n = 5) and IV (n = 8). By immunohistochemistry, six cases were positive for H3K27M, all showing concomitant loss of H3K27-me3. Next-generation sequencing was successfully performed in ten cases. Next-generation sequencing studies were successfully performed in four of the cases positive for H3K27M by immunohistochemistry, and all were confirmed as H3F3A K27M-mutant. Additional recurrent mutations identified included those of TERT promoter (n = 3), TP53 (n = 5), PPM1D (n = 3), NF1 (n = 3), ATRX (n = 2), and PIK3CA (n = 2). No HIST1H3B, HIST1H3C, IDH1, IDH2, or BRAF mutations were detected. Ten patients have died since first surgery, with a median survival of 13 months and 1 year of 46%. Median survival was 48.5 months for H3K27M-positive cases, compared to 1 month for those with TERT promoter mutation and 77 months for those harboring neither (p = 0.019). Median survival for cases with TP53 mutations was 11.5 months and for those with PPM1D mutations was 84 months. Our findings suggest that high-grade infiltrating gliomas of the spinal cord in adults represent a heterogeneous group of tumors, with variable outcomes possibly related to their molecular profiles.

Abnormal expression of microRNAs (miRNAs) contributes to glioma initiation. However, the expression of miRNAs in tumour tissue or blood of spinal cord glioma (SCG) patients, particularly in high-grade spinal gliomas (Grade IV) known as glioblastoma (GBM), remains largely unknown. In this study we aimed to determine differentially expressed miRNAs (DEmiRNAs) in the tissue and blood between spinal cord glioblastoma (SC-GBM) patients and low grade SCG (L-SCG) patients. Additionally, we predicted key miRNA targets and pathways that may be critical in glioma development using pathway and gene ontology analysis. A total of 74 miRNAs were determined to be differentially expressed (25 upregulated and 49 downregulated) in blood, while 207 miRNAs (20 up-regulated and 187 down-regulated) were identified in tissue samples. Gene ontology analysis revealed multicellular organism development and positive regulation of macromolecule metabolic process to be primarily involved. Pathway analysis revealed "Glioma", "Signalling pathways regulating pluripotency of stem cells" to be the most relevant pathways. miRNA-mRNA analysis revealed that hsa-miRNA3196, hsa-miR-27a-3p, and hsa-miR-3664-3p and their target genes are involved in cancer progression. Our study provides a molecular basis for SCG pathological grading based on differential miRNA expression.

Background: Primary spinal glioblastoma multiforme is a rare and aggressive spinal tumor with dismal outcomes CASE DESCRIPTION: We have presented an unusual case-the first, to the best of our knowledge, to be reported-with intratumoral hemorrhage and sudden-onset quadriplegia in a patients with primary spinal glioblastoma multiforme. The patient underwent emergency surgical decompression. The patient died after a prolonged intensive care unit stay., Conclusion: The tumor was positive for histone molecular alteration, H3K27M., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: MicroRNAs (miRs) regulate many biological processes, such as invasion, angiogenesis, and metastasis. Glioblastoma (GBM) patients with metastasis/metastatic dissemination have a very poor prognosis; therefore, inhibiting metastasis/metastatic dissemination has become an important therapeutic strategy for GBM treatment., Methods: Using 76 GBM tissues, we examined the expression levels of 23 GBM-related miRs and compared the miRs' expression levels between GBMs with metastasis/metastatic dissemination and GBMs without metastasis/metastatic dissemination. Using the bioinformatics web site, we searched the target genes of miRs. To analyze the function of target gene, several biological assays and survival analysis by the Kaplan-Meier method were performed., Results: We found that eight miRs were significantly decreased in GBM with metastasis/metastatic dissemination. By the bioinformatics analysis, we identified stanniocalcin-1 (STC1) as the most probable target gene against the combination of these miRs. Four miRs (miR-29B, miR-34a, miR-101, and miR-137) have predictive binding sites in STC1 mRNA, and mRNA expression of STC1 was downregulated by mimics of these miRs. Also, mimics of these miRs and knockdown of STC1 by siRNA suppressed invasion in GBM cells. GBM with metastasis/metastatic dissemination had significantly higher levels of STC1 than GBM without metastasis/metastatic dissemination. Finally, Kaplan-Meier analysis demonstrated that GBMs with high STC1 level had significantly shorter survival than GBMs with low STC1 level., Conclusions: STC1 may be a novel metastasis/metastatic dissemination promoting factor regulated by several miRs in GBM. Because STC1 is a secreted glycoprotein and functions via the autocrine/paracrine signals, inhibiting STC1 signal may become a novel therapeutic strategy for GBM.

Spinal cord astrocytomas (SCAs) have discernibly unique signatures in regards to epidemiology, clinical oncological features, genetic markers, pathophysiology, and research and therapeutic challenges. Overall, there are presently very limited clinical management options for high grade SCAs despite progresses made in validating key molecular markers and standardizing tumor classification. The endeavors were aimed to improve diagnosis, therapy design and prognosis assessment, as well as to define more effective oncolytic targets. Efficacious treatment for high grade SCAs still remains an unmet medical demand. This review is therefore focused on research state updates that have been made upon analyzing clinical characteristics, diagnostic classification, genetic and molecular features, tumor initiation cell biology, and current management options for SCAs. Particular emphasis was given to basic and translational research endeavors targeting SCAs, including establishment of experimental models, exploration of unique profiles of SCA stem cell-like tumor survival cells, characterization of special requirements for effective therapeutic delivery into the spinal cord, and development of donor stem cell-based gene-directed enzyme prodrug therapy. We concluded that precise understanding of molecular oncology, tumor survival mechanisms (e.g., drug resistance, metastasis, and cancer stem cells/tumor survival cells), and principles of Recovery Neurobiology can help to create clinically meaningful experimental models of SCAs. Establishment of such systems will expedite the discovery of efficacious therapies that not only kill tumor cells but simultaneously preserve and improve residual neural function., (Copyright © 2018. Published by Elsevier Inc.)

Objective: Spinal cord astrocytoma with intracranial dissemination carries a poor prognosis. The mechanisms leading to dissemination remain to be elucidated. A stem cell marker, CD133, was reported to predict recurrence patterns in intracranial glioblastoma. We evaluated the significance of CD133 as a putative prognostic biomarker to predict intracranial dissemination in spinal cord astrocytoma., Methods: This study included 14 consecutive patients with primary spinal cord astrocytoma treated from 1998 to 2014. Six of the patients were women and the patients' ages ranged from 12 to 75 years. Seven and 6 patients underwent open biopsy and partial resection of the tumors, respectively. After confirmation of the histologic diagnoses, all patients were treated with postoperative radiotherapy, chemotherapy, or a combination of both. To identify factors predictive of intracranial dissemination, we analyzed their clinical data including Ki-67 labeling index, and CD133 expression., Results: Intracranial dissemination was observed in 6 of 14 patients. All 6 patients died during the follow-up period. Of the 8 patients without intracranial dissemination, 5 survived (P = 0.02). Median survival for the patients with intracranial dissemination was 22.7 months. CD133 expression was significantly higher in patients with intracranial dissemination (P = 0.04), whereas other variables did not indicate the dissemination., Conclusions: The expression of CD133 can be an efficient biomarker to predict intracranial dissemination in spinal cord astrocytoma. Recognition of high CD133 expression in surgical specimens and early detection of intracranial dissemination is important for the clinical management of spinal cord astrocytoma., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background/aims: Spinal cord glioma is a highly aggressive malignancy that commonly results in high mortality due to metastasis, high recurrence and limited treatment regimens. This study aims to elucidate the effects of long non-coding RNA LINC01260 (LINC01260) on the proliferation, migration and invasion of spinal cord glioma cells by targeting Caspase recruitment domain family, member 11 (CARD11) via nuclear factor kappa B (NF-κB) signaling., Methods: The Multi Experiment Matrix (MEM) website was used for target gene prediction, and the DAVID database was used for analysis of the relationship between CARD11 and the NF-κB pathway. In total, 60 cases of glioma tissues and adjacent normal tissues were collected. Human U251 glioma cells were grouped into blank, negative control (NC), LINC01260 vector, CARD11 vector, siRNA-LINC01260, siRNA-CARD11, LINC01260 vector + CARD11 vector and LINC01260 + siRNA-CARD11 groups. A dual-luciferase reporter assay was conducted to verify the target relationship between LINC01260 and CARD11. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were employed to assess expression of LINC01260, E-cadherin, p53, CARD11, Ki67, N-cadherin, matrix metalloproteinase (MMP)-9, NF-κBp65 and NF-κBp50. MTT, flow cytometry, wound-healing and Transwell assays were performed to examine cell viability, the cell cycle, apoptosis, invasion and migration. Tumor growth was assessed through xenografts in nude mice., Results: CARD11 was confirmed to be a target gene of LINC01260 and was found to be involved in regulating the NF-κB pathway. Compared with adjacent normal tissues, glioma tissues showed reduced expression of LINC01260 and elevated expression of CARD11 and genes related to apoptosis, invasion and migration; activation of NF-κB signaling was also observed. In contrast to the blank and NC groups, an elevated number of cells arrested in G1 phase, increased apoptosis and reduced cell proliferation, invasion and number of cells arrested in S and G2 phases, as well as tumor growth were found for the LINC01260 vector and siRNA-CARD11 groups., Conclusions: Our findings demonstrate that overexpression of LINC01260 inhibits spinal cord glioma cell proliferation, migration and invasion by targeting CARD11 via NF-κB signaling suppression., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Cerebrospinal fluid (CSF) represents a promising source of cell-free DNA (cfDNA) for tumors of the central nervous system. A CSF-based liquid biopsy may obviate the need for riskier tissue biopsies and serve as a means for monitoring tumor recurrence or response to therapy. Spinal ependymomas most commonly occur in adults, and aggressive resection must be delicately balanced with the risk of injury to adjacent normal tissue. In patients with subtotal resection, recurrence commonly occurs. A CSF-based liquid biopsy matched to the patient's spinal ependymoma mutation profile has potential to be more sensitive then surveillance MRI, but the utility has not been well characterized for tumors of the spinal cord. In this study, we collected matched blood, tumor, and CSF samples from three adult patients with WHO grade II intramedullary spinal ependymoma. We performed whole exome sequencing on matched tumor and normal DNA to design Droplet Digital™ PCR (ddPCR) probes for tumor and wild-type mutations. We then interrogated CSF samples for tumor-derived cfDNA by performing ddPCR on extracted cfDNA. Tumor cfDNA was not reliably detected in the CSF of our cohort. Anatomic sequestration and low grade of intramedullary spinal cord tumors likely limits the role of CSF liquid biopsy.

Background: Alveolar soft part sarcoma (ASPS) is a rare, malignant soft-tissue neoplasm typically seen in young adults that possesses an unusual tendency to metastasize. Metastases to the intramedullary compartment of the spinal cord, however, are exceptionally rare and have not been described in the literature., Case Description: We report the case of a 23-year-old woman with disseminated ASPS to the lung and brain who presented with progressive lower-extremity weakness and loss of sensation after radiation and chemotherapy. Magnetic resonance imaging revealed a 1.3-cm avidly enhancing lesion within the central thoracic spinal cord at T3. A T2-T4 laminectomy was undertaken and resulted in a gross total resection. Histopathologically, the mass was composed of organoid nests containing epithelioid cells with eosinophilic, granular cytoplasm separated by sinusoidal spaces. Immunohistochemistry demonstrated convincing positive TFE3 staining. Postoperative imaging confirmed the complete resection of the mass, and her examination was notable for intact sensation and impaired motor function that gradually improved., Conclusions: A review of the literature found that the reported case represents the first instance of primary or metastatic ASPS in the spinal cord. Metastatic ASPS should thus be included in the differential diagnosis in patients with known disease and neurologic impairment or back pain. Imaging of the spine should then be considered., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Intramedullary spinal cord tumors (IMSCTs) are lethal diseases to many patients. The lack of adequate animal model has hampered the development of novel treatments. In the current study, a rodent intramedullary glioma model is established to study IMSCT progression. Fischer 344 rats received a intramedullary implantation of RG2 glioma cells. The neurological state of each rat was evaluated on daily basis using the Basso, Beattie and Bresnahan (BBB) scale. Rats implanted with RG2 cells developed significant hind limb paraplegia 20 days after implantation. Magnetic resonance imaging (MRI) scans after three weeks revealed significant intramedullary RG2 tumors in the rats. Forty days post implantation, rats were sacrificed for histopathological examination. Neuro-imaging and HE staining cross sections confirmed intramedullary RG2 glioma cells invading to the spinal cord. Thus, our model displayed many of the same invasive characteristics as human IMSCTs. This model should be a reliable and reproducible methodology to correlate well with the features of human IMSCT.

Background: Despite an increasing number of O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET studies in supratentorial gliomas, studies regarding the usefulness of 18F-FET PET in brainstem and spinal cord gliomas to date remain scarce., Methods: Thirty-six 18F-FET PET scans were performed in 29 patients with brainstem (n = 29 scans) or spinal cord glioma (n = 7 scans). In 32 of 36 PET scans, a dynamic acquisition was performed. Fifteen scans in 15 patients were performed to assess newly diagnosed lesions, and 21 scans were obtained during follow-up: for diagnosing tumor progression (n = 15 scans in 14 patients) as well as for treatment monitoring (n = 6 scans in 3 patients). Four patients underwent additional serial scans (range, 1-2), and 3 of these 4 patients were examined for more than one indication. Maximum and mean tumor/brain ratios (TBRmax/mean) of 18F-FET uptake (20-40 min post injection) as well as kinetic 18F-FET uptake parameters were determined. Final diagnoses were confirmed histologically (54%) or by clinical follow-up (46%)., Results: In all newly diagnosed high-grade (n = 3 patients) and in 5 of 11 patients with low-grade gliomas, 18F-FET uptake was increased (TBRmax ≥2.5 and/or TBRmean ≥1.9). In 2 patients with newly diagnosed gliomas without MR contrast enhancement, 18F-FET PET nevertheless showed increased metabolism. At suspected progression, the combination of TBRs with kinetic 18F-FET parameters correctly identified presence or absence of progressive disease in 9 of 11 patients (82%)., Conclusions: This preliminary study suggests that 18F-FET PET adds valuable diagnostic information in brainstem and spinal cord glioma, particularly when the diagnostic information derived from MRI is equivocal., (© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

The aim of this study was to prepare and characterize a new nanocarrier for oral delivery of tamoxifen citrate (TMC) as a lipophilic oral administrated drug. This drug has low oral bioavailability due to its low aqueous solubility. To enhance the solubility of this drug, the microemulsion system was applied in form of oil-in-water. Sesame oil and Tween 80 were used as drug solvent oil and surfactant, respectively. Two different formulations were prepared for this purpose. The first formulation contained edible glycerin as co-surfactant and the second formulation contained Span 80 as a mixed surfactant. The results of characterization showed that the mean droplet size of drug-free samples was in the range of 16.64-64.62nm with a PDI value of <0.5. In a period of 6months after the preparation of samples, no phase sedimentation was observed, which confirmed the high stability of samples. TMC with a mass ratio of 1% was loaded in the selected samples. No significant size enlargement and drug precipitation were observed 6months after drug loading. In addition, the drug release profile at experimental environments in buffers with pH=7.4 and 5.5 showed that in the first 24h, 85.79 and 100% of the drug were released through the first formulation and 76.63 and 66.42% through the second formulation, respectively. The in-vivo results in BALB/c female mice showed that taking microemulsion form of drug caused a significant reduction in the growth rate of cancerous tumor and weight loss of the mice compared to the consumption of commercial drug tablets. The results confirmed that the new formulation of TMC could be useful for breast cancer treatment., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The adult rodent spinal cord presents an inhibitory environment for donor cell survival, impeding efficiency for xenograft-based modeling of gliomas. We postulated that mild thermal preconditioning may influence the fate of the implanted tumor cells. To test this hypothesis, high-grade human astrocytoma G55 and U87 cells were cultured under 37C and 38.5C to mimic regular experimental or core body temperatures of rodents, respectively. In vitro, the 38.5C-conditioned cells, relative to 37C, grew slightly faster. Compared to U87 cells, G55 cells demonstrated a greater response to the temperature difference. Hyperthermal culture markedly increased production of Hsp27 in most G55 cells, but only promoted transient expression of cancer stem cell marker CD133 in a small cell subpopulation. We subsequently transplanted G55 cells following 37C or 38.5C culture into the C2 or T10 spinal cord of adult female immunodeficient rats (3 rats/each locus/per temperature; total: 12 rats). Systematic analyses revealed that 38.5C-preconditioned G55 cells grew more malignantly at either C2 or T10 as determined by tumor size, outgrowth profile, resistance to bolus intratumor administration of 5-fluorouracil (0.1 mol), and posttumor survival (p0.05; n=6/group). Therefore, thermal preconditioning of glioma cells may be an effective way to influence the in vitro and in vivo oncological contour of glioma cells. Future studies are needed for assessing the potential oncogenic modifying effect of hyperthermia regimens on glioma cells.

Objective: To investigate the clinicopathologic features of glioneuronal tumor with neuropil-like island (GTNI)., Methods: Four cases of intracranial and spinal GTNI, including three cases of WHO grade Ⅲ, and one case of WHO grade Ⅱ with grade Ⅲ recurrence. HE and immunohistochemical (IHC) staining were used for pathologic analysis. Fluorescence in situ hybridization (FISH) was used to detect tumor genetic changes. Related literatures were reviewed., Results: Microscopically, neuropil-like islands of varying sizes were seen within a background of glial proliferation, which showed features of astrocytoma or oligoastrocytoma. Neuropil-like islands were focal or circumscribed oval islands of varying sizes. Focally ganglion-like cells were seen. IHC staining revealed that in neuropil-like island area, the neuronal nuclei (Neu-N) as well as the cells around the neuropil-like island expressed oligodendrocyte lineage transcription factor-2 (Olig-2), and synaptophysin. The background glioma cells expressed S-100, glial fibrillary acidic protein (GFAP), vimentin and Olig-2, and the number of p53 positive cells was 10%-50%.In the neuropil-like island area, the Ki-67 labeling index was less than 3%, while in the astrocytoma area it was around 10%-25%.By FISH testing, four cases were no deletion of 1p/19q and PTEN, also no amplification of epidermal growth factor receptor., Conclusions: GTNI is more common in adults. 1p/19q deletions are uncommon in GTNI, only seen in a few cases with background oligodendroglioma. The prognosis is related to WHO grading. GTNI often recurs locally, and the prognosis is not good, especially in the spinal cord GTNI. The recommended treatment includes tumor resection combined with radiotherapy and chemotherapy.

Introduction: Intramedullary tumors account for 2-4% of all CNS neoplasms. Surgical resection is challenging because of aggravated neurological impairment in up to 64% of patients. We analyzed a consecutive series of patients with intramedullary tumors and focused on the extent of resection, functional outcome, and tumor recurrence., Methods: 53 patients (23 women and 30 men; mean age 46.3 years) were included who had undergone microsurgical resection for intramedullary spinal tumors. We reviewed the patient records for tumor size, edema, intratumoral hemorrhage, consistency, midline detection, resection method, extent of resection, histopathology, and recurrence. Outcome was measured by the Karnofsky Score (KPI), the McCormick score (MCS), and the Medical Research Council Neurological Performance Score (MRC-NPS)., Results: The most frequent diagnosis was ependymoma (37.7%), lymphoma (13.2%) and astrocytoma (11.3%). The majority of tumors were located in the thoracic spine (62.2%). Gross total resection was achieved in 73.6% and most successful in patients with ependymal histology (p<0.01). Tumor recurrence - observed in 11.3% - was significantly associated with age >65 years, astrocytic histology, higher tumor grades, and higher Ki-67 labeling. At follow-up, MCS and MRC-NPS showed significantly better results than prior to resection (p<0.001), and pain and sensory deficits had improved in 67.9% and 64.2% of patients, respectively. Microsurgical resection improved the neurological status significantly. Pain and sensory deficits showed higher improvement rates than paresis and vegetative dysfunction., Conclusion: Our data help identify patients at risk of tumor recurrence and classify the course of postoperative neurological performance., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Injection of a PDGF-B expressing retrovirus into the subcortical white matter of adult rats induces the rapid formation of brain tumors that have the histological features of glioblastoma. In contrast, when the same retrovirus is injected into the spinal cord of adult rats the resulting tumors are more indolent and display a unique histology characterized by nests of tumor cells separated by a dense vascular network without areas of necrosis. To study whether these differences are determined by the tumor cell of origin or due to microenvironmental influences, we conducted a series of transplantation experiments. Cells were independently isolated from PDGF-induced brain and cord tumors then subsequently transplanted into naive rat forebrains and spinal cords. The resulting tumors were characterized by histological analysis, marker expression profiling, PDGFR subtyping, and latency to tumor-induced morbidity. Tumor phenotypes were found to be consistently predicted by the tissue into which they were transplanted rather than by the tissue of origin. These results suggest that tumor microenvironment rather than the tumor cell of origin may be the primary determinant of glioma phenotype in the model presented.

Hemangioblastomas consist of 10-20% neoplastic "stromal" cells within a vascular tumor cell mass of reactive pericytes, endothelium and lymphocytes. Familial cases of central nervous system hemangioblastoma uniformly result from mutations in the Von Hippel-Lindau (VHL) gene. In contrast, inactivation of VHL has been previously observed in only a minority of sporadic hemangioblastomas, suggesting an alternative genetic etiology. We performed deep-coverage DNA sequencing on 32 sporadic hemangioblastomas (whole exome discovery cohort n = 10, validation n = 22), followed by analysis of clonality, copy number alteration, and somatic mutation. We identified somatic mutation, loss of heterozygosity and/or deletion of VHL in 8 of 10 discovery cohort tumors. VHL inactivating events were ultimately detected in 78% (25/32) of cases. No other gene was significantly mutated. Overall, deep-coverage sequence analysis techniques uncovered VHL alterations within the neoplastic fraction of these tumors at higher frequencies than previously reported. Our findings support the central role of VHL inactivation in the molecular pathogenesis of both familial and sporadic hemangioblastomas.

Perineural tumor invasion of intrapancreatic nerves, neurogenic inflammation, and tumor metastases along extrapancreatic nerves are key features of pancreatic malignancies. Animal studies show that chronic pancreatic inflammation produces hypertrophy and hypersensitivity of pancreatic afferents and that sensory fibers may themselves drive inflammation via neurogenic mechanisms. Although genetic mutations are required for cancer development, inflammation has been shown to be a precipitating event that can accelerate the transition of precancerous lesions to cancer. These observations led us to hypothesize that inflammation that accompanies early phases of pancreatic ductal adenocarcinoma (PDAC) would produce pathologic changes in pancreatic neurons and innervation. Using a lineage-labeled genetically engineered mouse model of PDAC, we found that pancreatic neurotrophic factor mRNA expression and sensory innervation increased dramatically when only pancreatic intraepithelial neoplasia were apparent. These changes correlated with pain-related decreases in exploratory behavior and increased expression of nociceptive genes in sensory ganglia. At later stages, cells of pancreatic origin could be found in the celiac and sensory ganglia along with metastases to the spinal cord. These results demonstrate that the nervous system participates in all stages of PDAC, including those that precede the appearance of cancer., (©2014 AACR.)

Astrocytoma grade IV (glioblastoma multiforme) is the most common and most malignant tumor of the central nervous system and is currently noncurable. Here, we have examined a population-based cohort of 47 patients with grade IV astrocytoma, who underwent tumor surgery at Sahlgrenska University Hospital in Sweden and who survived after surgery for less than 200 days (short survivors, 28 patients) and more than 500 days (long survivors, 19 patients). For each tumor, we ascertained information on patient age, sex, tumor location, oncological treatment, and survival after surgery. The analysis of the tumor volume and the extent of tumor resection (incomplete versus complete resection of the macroscopic tumor) was made retrospectively from the preoperative radiological investigations and, when available, also from postoperative radiology. We performed semiquantitative immunohistochemical evaluation of the presence of intermediate filament (nanofilament) proteins glial fibrillary acidic protein, vimentin, nestin, and synemin in tumor cells. The intermediate filament system helps cells and tissues to cope with various types of stress, and thus, it might affect the malignant potential of grade IV astrocytoma. We propose a subclassification of astrocytomas grade IV with respect to the expression of the intermediate filament proteins glial fibrillary acidic protein, vimentin, nestin, and synemin, namely, type A, B, and C. Our results suggest that the expression of the intermediate filament proteins glial fibrillary acidic protein, vimentin, nestin, and synemin is coregulated in grade IV astrocytomas. The expression patterns of the intermediate filament proteins in astrocytoma type A, B, and C might have biological and clinical significance., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Gliofibromas represent a relativel rare variant of astrocytoma marked by a mixture of astrocytoma and a benign mesenchymal component, usually fibroblastic with collagen deposition. The exact nature of these tumors, due to their rarity, is still uncertain. This paper reports a case of spinal cord gliofibroma arising in a 19-year-old female who presented with headaches. Imaging studies suggested widespread, multifocal tumor. Histologically, the tumor was marked by a low grade astrocytoma component (GFAP and S-100 positive) intermixed with bands of collagen. A Ki-67 labeling index of 1.9% was observed. The literature on gliofibromas arising in the spinal cord is reviewed.

Heterologous expression of Kir channels offers a tool to modulate excitability of neurons which provide insight into Kir channel functions in general. Inwardly-rectifying K+ channels (Kir channels) are potential candidate proteins to hyperpolarize neuronal cell membranes. However, heterologous expression of inwardly-rectifying K+ channels has previously proven to be difficult. This was mainly due to a high toxicity of the respective Kir channel expression. We investigated the putative role of a predominantly glial-expressed, weakly rectifying Kir channel (Kir4.1 channel subunit; KCNJ10) in modulating electrophysiological properties of a motoneuron-like cell culture (NSC-34). Transfection procedures using an EGFP-tagged Kir4.1 protein in this study proved to have no toxic effects on NSC-34 cells. Using whole cell-voltage clamp, a substantial increase of inward rectifying K+ currents as well as hyperpolarization of the cell membrane was observed in Kir4.1-transfected cells. Na+ inward currents, observed in NSC-34 controls, were absent in Kir4.1/EGFP motoneuronal cells. The Kir4.1-transfection did not influence the NaV1.6 sodium channel expression. This study demonstrates the general feasibility of a heterologous expression of a weakly inward-rectifying K+ channel (Kir4.1 subunit) and shows that in vitro overexpression of Kir4.1 shifts electrophysiological properties of neuronal cells to a more glial-like phenotype and may therefore be a candidate tool to dampen excitability of neurons in experimental paradigms.

Zoledronic acid (ZOL), a nitrogen-containing compound, is effective in the treatment of skeletal disorders, but its long-term use in high doses gives rise to complications such as osteonecrosis. We aimed to investigate the effect of low-dose ZOL on the expression of the neural cell adhesion molecule (NCAM), which may be correlated with tumor growth and spinal cord metastasis in lung adenocarcinoma with neuroendocrine differentiation. First, we used the small hairpin RNA technique to directly knock down NCAM expression in cells of a murine lung adenocarcinoma line, line 1 cells, and found that the tumor cells generated showed lower invasive capacity, slower tumor growth, and lesser tendency for spinal cord metastasis than control cells. Further, ZOL decreased NCAM expression and invasiveness in line 1 tumor cells in vitro. Line 1/lacZ cells, a stable clone tagged with the lacZ gene, were introduced into mice, followed by ZOL treatment (1 μg/kg/weekly). Low-dose ZOL significantly reduced spinal cord metastasis probably through reduced NCAM expression in vivo. These findings indicated that NCAM is involved in tumor growth and spinal cord metastasis of lung adenocarcinoma with neuroendocrine differentiation. Treatment with low-dose ZOL can reduce NCAM expression that may contribute toward reduced spinal cord metastasis, suggesting that NCAM is an alternative therapeutic target and that the low-dose ZOL treatment protocol is a reasonable approach for its treatment.

Glioneuronal tumors with neuropil-like islands are rare. The 1st reported cases were localized in the cerebral hemispheres of adults, showed homogeneous histopathologic features (infiltrating astrocytic growth and neuropil-like islands rimmed by neuronal cells), and had an unfavorable behavior. We report 3 pediatric cases (1 boy and 2 girls, ages 4, 6, and 8 years, respectively). The boy had a cerebral tumor, and the girls had a spinal tumor. The younger girl also had multiple posterior fossa lesions. The boy and older girl underwent a gross total resection. The younger girl underwent a subtotal resection of the spinal tumor; posterior fossa lesions were not surgically treated. The boy and younger girl are in complete remission at 33 and 24 months, respectively, after surgery and subsequent high-dose chemoradiotherapy. The older girl had a recurrence that was partially resected. Afterward, she started high-dose chemoradiotherapy and had an optimal radiologic response at 4 months follow up. Microscopically, the common denominator was the presence of synaptophysin-positive neuropil-like islands. One tumor showed ependymal features (pseudorosettes and punctate epithelial membrane antigen immunopositivity). Two tumors had 1p deletion. 19q deletion, MGMT gene promoter methylation, EGFR amplifications or polysomy, and EGFR, IDH1, IDH2, and TP53 genes mutation analyses yielded negative results. In conclusion, glioneuronal tumor with neuropil-like islands can affect children, arise in the spinal cord, and show ependymal features in its glial component. A high-dose chemoradiotherapy program is effective.

We present 2 rare cases of mixed schwannoma with meningioma. The first case was sporadic, in a 38-year-old female in cervical spine (C₂). The second case was a 24-year-old female, associated with NF-2, involving bilateral cerebellopontine angle with extension into the left cavernous sinus, sellar region with erosion of the petrous ridge and multiple intradural extramedullary lesions in the spinal cord suggestive of neurofibromas. To date only 12 cases of such tumors are documented in the literature. To the best of our knowledge this is the first case of sporadic mixed schwannoma with meningioma in cervical spine (C₂).

Object: Primary spinal cord ependymomas (EPNs) are rare in children, comprising classical WHO Grade II and III tumors and Grade I myxopapillary ependymomas (MEPNs). Despite their benign histology, recurrences and neural-axis dissemination have been reported in up to 33% MEPNs in the pediatric population. Treatment options beyond resection are limited, and little is known about their tumorigenesis. The purpose of this study was to explore the tumor biology and outcomes in a consecutive series of pediatric patients treated at a single institution., Methods: The authors performed a retrospective clinicopathological review of 19 patients at a tertiary referral children's hospital for resection of a spinal cord ependymoma. The population included 8 patients with a pathological diagnosis of MEPN and 11 patients with a pathological diagnosis of spinal EPN (10 cases were Grade II and 1 case was Grade III). The upregulation of the following genes HOXB13, NEFL, PDGFRα, EGFR, EPHB3, AQP1, and JAGGED 1 was studied by immunohistochemistry from archived paraffin-embedded tumor samples of the entire cohort to compare the expression in MEPN versus EPN., Results: Gross-total resection was achieved in 75% of patients presenting with MEPNs and in 100% of those with EPNs. The average follow-up period was 79 months for the MEPN subset and 53 months for Grade II/III EPNs. Overall survival for both subsets was 100%. However, event-free survival was only 50% for patients with MEPNs. Of note, in all cases involving MEPNs that recurred, the patients had undergone gross-total resection on initial surgery. In contrast, there were no tumor recurrences in patients with EPNs. Immunohistochemistry revealed no significant differences in protein expression between the two tumor types with the exception of EPHB3, which demonstrates a tendency to be positive in MEPNs (6 reactive tumors of 9) rather than in EPN (2 reactive tumors of 10)., Conclusions: The authors' experience shows that, following a gross-total resection, MEPNs are more likely to recur than their higher-grade counterpart, EPNs. This supports the recommendation for close long-term radiological follow-up of pediatric patients with MEPNs to monitor for recurrence, despite the tumor's low-grade histological feature. No significant difference in the protein expression of HOXB13, NEFL, PDGFRα, EGFR, EPHB3, AQP1, and JAGGED 1 was present in this selected cohort of pediatric patients.

Although histopathological diagnosis of spinal cord astrocytomas is important for postoperative treatment planning and prognosis, there is a lack of reliable immunohistochemical markers. The purpose of our study was to assess the expression pattern of GFAP-δ in spinal cord astrocytomas in human patients and to evaluate the utility of GFAP-δ as an immunohistochemical diagnostic marker. A total of 22 patients with spinal cord astrocytic tumors were included in this study. Patients were classified according to the WHO designation of human astrocytic tumors; three patients had grade 1 astrocytomas, 14 had grade 2, and five had Grade 3. Normal control spinal cord tissues were obtained at autopsy from the cervical spinal cords of ten patients with no history of cervical trauma or neurological disease. We evaluated BRAF, IDH1, GFAP, and GFAP-δ immunoreactivity in control tissues and astrocytomas. In normal control tissues, GFAP immunoreactivity was detected in astrocytes whereas GFAP-δ immunoreactivity was observed in very few astrocytes adjacent to the subpial layer of the spinal cord. GFAP-δ immunoreactivity was significantly correlated with spinal cord astrocytoma grade in astrocytomas compared to that in normal control tissues. The optical density of GFAP-δ increased significantly with astrocytoma grade (correlation coefficient, R (2) = 0.680). Also, BRAF and IDH1 immunoreactivity were detected in astrocytoma. We suggest that GFAP-δ may be an additional, reliable histopathological diagnostic marker for spinal cord astrocytomas.

Tanycytic ependymoma is an uncommon but well-recognized variant of ependymoma. Here we report a case of tanycytic ependymoma occurring at the region of filum terminale in a 44-year male who presented with low backache, bilateral lower limb weakness and urinary incontinence. MR imaging in this patient showed a lesion that was composed of solid and cystic components and was suggestive of ependymoma. The filum terminale region is an extremely unusual location for the occurrence of tanycytic ependymoma. To the best of our knowledge this is the third case of tanycytic ependymoma occurring in the filum terminale region., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Ependymomas constitute the most common type of primary spinal cord tumors, and are subclassified as myxopapillary ependymoma, classic ependymoma, and anaplastic ependymoma. Ependymomas can be further subclassified based on morphologic phenotype: cellular, papillary, tanycytic, clear cell, pigmented and epithelioid. Giant cell ependymoma (GCE), a rare variant, has recently been described. Reported cases have exhibited a wide anatomic distribution, including spinal cord, cerebrum and cerebellum. We report here three cases of GCE, arising from cerebrum in a 5-year-old girl, spinal cord in a 34-year-old female and cerebellum in an 86-year-old female respectively. Histologically those cases showed prominent pleomorphic giant cells with focal perivascular pseudorosettes in all cases. Tumor cells were immunopositive for GFAP and EMA. Only the first case was qualified for anaplastic ependymoma. No recurrence was noted in these three cases after 57, 46 and 6 months of follow-up respectively. By reviewing the literature, GCEs arising from spinal cord and cerebellum tended to have low-grade morphology while supratentorially located GCEs tended to have anaplastic features. GCEs were preferentially located in extraventricular regions. Anaplastic GCEs in adult population seemed to pursue a more aggressive behavior. Gross total resection should still be the main treatment for GCEs.

Background: High-grade gliomas of the spinal cord are poorly understood tumors that are very commonly associated with bad outcomes. The transforming effects of platelet-derived growth factor (PDGF) on spinal cord glial progenitor cells may play an important role in the development of these tumors., Objective: To investigate the possible tumor-initiating effects of PDGF overexpression in the spinal cord, we delivered a PDGF retrovirus directly into the substance of the spinal cord., Methods: The spinal cords of wild-type adult rats were surgically exposed and injected with 10⁶ colony-forming units of a green fluorescent protein-tagged, PDGF-expressing retrovirus. A control virus was injected to assess the cell types that become infected during retroviral delivery to the spinal cord., Results: It was observed that PDGF overexpression in the spinal cord causes morbidity from high-grade intramedullary glioma formation between 27 and 49 days after PDGF retrovirus injection. Retroviral transduction was highly efficient with 100% of injected animals displaying the tumor phenotype. The tumors produced were highly proliferative, were locally invasive, and displayed the immunophenotype of virus-targeted glial progenitor cells (Olig2+PDGFR+NG2+GFAP-)., Conclusion: PDGF is capable of driving glial progenitor cells within the adult spinal cord to form high-grade gliomas. Further investigation of PDGF signaling in the spinal cord is needed to better understand and treat these devastating tumors.

Abnormal signaling through the platelet-derived growth factor receptor (PDGFR) has been proposed as a possible mechanism of spinal cord glioma initiation and progression. However, the extent of PDGFR expression in human spinal cord gliomas remains unknown. In this study we perform immunohistochemical analysis of PDGFRα expression in a series of 33 primary intramedullary spinal cord gliomas of different types and grades. PDGFRα was seen to be expressed in a significant subset of these tumors across all major glioma types including ependymoma, oligodendroglioma, pilocytic astrocytoma, astrocytoma, and glioblastoma. These results support the hypothesis that growth factor signaling through the PDGFR may be important for the development of at least a subset of human spinal cord gliomas. Further studies investigating the prognostic significance of PDGFR expression as well as the role of PDGF signaling on the development of intramedullary spinal cord gliomas are warranted.