Ependymomas of the spinal region in adults: Clinical and pathological features and MYCN expression levels in spinal ependymomas and myxopapillary ependymomas.

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.

Malignant transformation of NF1-associated spinal astrocytoma with loss of ATRX expression during the course: A case report.

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.

Bioinformatics analysis of microarray data reveals epithelial-mesenchymal-transition in pediatric ependymoma.

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.

LncRNA TPT1-AS1 Sponges miR-23a-5p in Glioblastoma to Promote Cancer Cell Proliferation.

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.

Clinical Features and Outcomes of Primary Spinal Cord Glioblastoma: A Single-Center Experience and Literature Review.

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.

Expression Patterns of Hypoxia-Inducible Factors, Proinflammatory, and Neuroprotective Cytokines in Neuroepithelial Tissues of Lumbar Spinal Lipomas-A Pilot Study.

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-1ß (IL-1ß)/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-1ß-/IL-1ß 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.

Spinal Cord Tumor Microenvironment.

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.

Prognostic value of H3K27me3 in children with ependymoma.

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.

Analysis of PD-L1 expression and T cell infiltration in different molecular subgroups of diffuse midline gliomas.

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.

Downregulated long non-coding RNA LINC00899 inhibits invasion and migration of spinal ependymoma cells via RBL2-dependent FoxO pathway.

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.

Comparison of Alterations in miRNA Expression in Matched Tissue and Blood Samples during Spinal Cord Glioma Progression.

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.

Spinal cord high-grade infiltrating gliomas in adults: clinico-pathological and molecular evaluation.

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.

H3K27M-Positive Primary Spinal Glioblastoma Presenting with Hemorrhage-A Rare Clinical Entity.

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.

MicroRNA regulating stanniocalcin-1 is a metastasis and dissemination promoting factor in glioblastoma.

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: progresses in experimental and clinical investigations for developing recovery neurobiology-based novel therapies.

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.

Long Non-Coding RNA LINC01260 Inhibits the Proliferation, Migration and Invasion of Spinal Cord Glioma Cells by Targeting CARD11 Via the NF-κB Signaling Pathway.

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.

Expression of CD133 as a Putative Prognostic Biomarker to Predict Intracranial Dissemination of Primary Spinal Cord Astrocytoma.

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.

A pilot study on the use of cerebrospinal fluid cell-free DNA in intramedullary spinal ependymoma.

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.