-
Neuro-oncology Jun 2022The risk profile for posterior fossa ependymoma (EP) depends on surgical and molecular status [Group A (PFA) versus Group B (PFB)]. While subtotal tumor resection is...
BACKGROUND
The risk profile for posterior fossa ependymoma (EP) depends on surgical and molecular status [Group A (PFA) versus Group B (PFB)]. While subtotal tumor resection is known to confer worse prognosis, MRI-based EP risk-profiling is unexplored. We aimed to apply machine learning strategies to link MRI-based biomarkers of high-risk EP and also to distinguish PFA from PFB.
METHODS
We extracted 1800 quantitative features from presurgical T2-weighted (T2-MRI) and gadolinium-enhanced T1-weighted (T1-MRI) imaging of 157 EP patients. We implemented nested cross-validation to identify features for risk score calculations and apply a Cox model for survival analysis. We conducted additional feature selection for PFA versus PFB and examined performance across three candidate classifiers.
RESULTS
For all EP patients with GTR, we identified four T2-MRI-based features and stratified patients into high- and low-risk groups, with 5-year overall survival rates of 62% and 100%, respectively (P < .0001). Among presumed PFA patients with GTR, four T1-MRI and five T2-MRI features predicted divergence of high- and low-risk groups, with 5-year overall survival rates of 62.7% and 96.7%, respectively (P = .002). T1-MRI-based features showed the best performance distinguishing PFA from PFB with an AUC of 0.86.
CONCLUSIONS
We present machine learning strategies to identify MRI phenotypes that distinguish PFA from PFB, as well as high- and low-risk PFA. We also describe quantitative image predictors of aggressive EP tumors that might assist risk-profiling after surgery. Future studies could examine translating radiomics as an adjunct to EP risk assessment when considering therapy strategies or trial candidacy.
Topics: Ependymoma; Humans; Machine Learning; Magnetic Resonance Imaging; Prognosis; Retrospective Studies
PubMed: 34850171
DOI: 10.1093/neuonc/noab272 -
British Journal of Cancer Jan 2007Ependymomas are tumours that arise throughout the central nervous system. Little is known regarding the aberrant cellular and molecular processes that generate these... (Review)
Review
Ependymomas are tumours that arise throughout the central nervous system. Little is known regarding the aberrant cellular and molecular processes that generate these tumours. This lack of knowledge has hampered efforts to reduce the significant mortality and morbidity that are associated with ependymoma. Here, we review recent data that suggest that radial glia are cells of origin of ependymoma, and discuss the processes that might transform these neural progenitors into ependymoma cancer stem cells.
Topics: Brain Neoplasms; Cell Transformation, Neoplastic; Central Nervous System Neoplasms; Ependymoma; Humans; Models, Biological; Neoplastic Stem Cells; Neuroglia; Signal Transduction
PubMed: 17179988
DOI: 10.1038/sj.bjc.6603519 -
Folia Neuropathologica 2011Ependymal tumours are relatively uncommon primary neoplasms of the central nervous system. Histological criteria distinguishing ependymoma and anaplastic ependymoma are... (Review)
Review
AIM
Ependymal tumours are relatively uncommon primary neoplasms of the central nervous system. Histological criteria distinguishing ependymoma and anaplastic ependymoma are not clear-cut and other parameters are required to allow more precise prognostication in these tumours. We analysed the histological and immunohistochemical features of these tumours (Ki-67, cyclin D1, EGFR, hTERT, Olig2) and correlated them with the clinical outcome.
MATERIAL AND METHODS
We analysed 39 patients with grade II ependymoma (30) and anaplastic ependymoma (9). Twenty-eight tumours developed in children and the remaining 11 patients were adults with intracranial and intraspinal tumours. Eighteen patients died during the follow-up period.
RESULTS AND CONCLUSIONS
Overall survival was reduced significantly for paediatric patients and patients with intracranial tumour. High-grade tumours, increased mitotic index and increased cellularity had an unfavourable influence on survival. Other histological parameters such as nuclear atypia, necrosis and microvascular proliferation did not alter the survival rate. Increased Ki-67 and cyclin D1 indices correlated with worse prognosis. Furthermore, any level of cyclin D1 expression in WHO grade II ependymomas was strongly associated with higher risk of death. No correlation was identified between Olig2, EGFR and hTERT expression and the outcome of the patients.
Topics: Adolescent; Adult; Biomarkers, Tumor; Central Nervous System Neoplasms; Child; Child, Preschool; Ependymoma; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Middle Aged; Prognosis; Young Adult
PubMed: 21845537
DOI: No ID Found -
Acta Neuropathologica Mar 2021Two distinct genetically defined entities of ependymoma arising in the supratentorial compartment are characterized by the presence of either a C11orf95-RELA or a...
Two distinct genetically defined entities of ependymoma arising in the supratentorial compartment are characterized by the presence of either a C11orf95-RELA or a YAP-MAMLD1 fusion, respectively. There is growing evidence that supratentorial ependymomas without these genetic features exist. In this study, we report on 18 pediatric non-RELA/non-YAP supratentorial ependymomas that were systematically characterized by means of their histology, immunophenotype, genetics, and epigenomics. Comprehensive molecular analyses included high-resolution copy number analysis, methylation profiling, analysis of fusion transcripts by Nanostring technology, and RNA sequencing. Based upon histological and immunohistochemical features two main patterns were identified-RELA-like (n = 9) and tanycytic ependymomas (n = 6). In the RELA-like group histologically assigned to WHO grade III and resembling RELA-fused ependymomas, tumors lacked nuclear expression of p65-RelA as a surrogate marker for a pathological activation of the NF-κB pathway. Three tumors showed alternative C11orf95 fusions to MAML2 or NCOA1. A methylation-based brain tumor classifier assigned two RELA-like tumors to the methylation class "EP, RELA-fusion"; the others demonstrated no significant similarity score. Of the tanycytic group, 5/6 tumors were assigned a WHO grade II. No gene fusions were detected. Methylation profiling did not show any association with an established methylation class. We additionally identified two astroblastoma-like tumors that both presented with chromothripsis of chromosome 22 but lacked MN1 breaks according to FISH analysis. They revealed novel fusion events involving genes in chromosome 22. One further tumor with polyploid cytogenetics was interpreted as PFB ependymoma by the brain tumor methylation classifier but had no relation to the posterior fossa. Clinical follow-up was available for 16/18 patients. Patients with tanycytic and astroblastoma-like tumors had no relapse, while 2 patients with RELA-like ependymomas died. Our data indicate that in addition to ependymomas discovered so far, at least two more supratentorial ependymoma types (RELA-like and tanycytic) exist.
Topics: Adaptor Proteins, Signal Transducing; Adolescent; Child; Child, Preschool; Ependymoma; Female; Humans; Infant; Male; Supratentorial Neoplasms; Transcription Factor RelA; Transcription Factors; YAP-Signaling Proteins
PubMed: 33481105
DOI: 10.1007/s00401-020-02260-5 -
Turkish Neurosurgery 2024To identify ependymoma (EPN) driver genes and key pathways, and also to illuminate the connection between prognosis of EPN patients and expression levels of driver genes.
AIM
To identify ependymoma (EPN) driver genes and key pathways, and also to illuminate the connection between prognosis of EPN patients and expression levels of driver genes.
MATERIAL AND METHODS
The gene expression profiles of GSE50161, GSE66354, GSE74195, and GSE86574 were analyzed to figure out the differentially expressed genes (DEGs) between tissue of EPN and normal brain samples. To harvest the enrichment functions, pathways and hub genes, the Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein-protein interaction (PPI) network analysis were made. Subsquently, survival analysis was performed in 325 patients to illuminate the connection between prognosis of EPN and expression levels of hub genes.
RESULTS
20 functions and 10 pathways which were up- or downregulated between the EPN and normal samples were revealed applying GO and KEGG analysis. Mutual hub genes were TP53, TOP2A, CDK1, PCNA, and ACTA2. The pathways of Hedgehog and notch signaling, mismatch repair (MMR), and retrograde endocannabinoid were significantly abnormally regulated in EPN tissue. Survival analysis revealed favorable progression-free (PFS) and overall (OS) survival in EPN patients with low expression of TOP2A, CDK1, PCNA, and ACTA2 (p < 0.05).
CONCLUSION
Patients with lower expression of TOP2A, CDK1, PCNA, and ACTA2 had a longer OS and PFS. The differential expressed genes identified and the key pathways selected in this research provided unprecedented and promising targets for diagnosis and treatment of EPN patients.
Topics: Humans; Proliferating Cell Nuclear Antigen; Brain; DNA Mismatch Repair; Ependymoma; Gene Expression
PubMed: 30649797
DOI: 10.5137/1019-5149.JTN.21876-17.5 -
Ugeskrift For Laeger Nov 2015Subcutaneous myxopapillary ependymoma is a very rare entity, and to our knowledge this is the first published case from Denmark. A previously healthy 32-year-old male...
Subcutaneous myxopapillary ependymoma is a very rare entity, and to our knowledge this is the first published case from Denmark. A previously healthy 32-year-old male presented with subcutaneous swelling and tenderness located at the top of the intergluteal cleft. The circular soft tumour, measuring 1.7 × 1.7 × 1.2 cm, was removed surgically. After histopathological examination with several immunohistochemical and special stainings, the diagnosis surprisingly was subcutaneous myxopapillary ependymoma. The tumour was removed with free margins and no metastases were found on follow-up CT- and MRI scans.
Topics: Adult; Ependymoma; Humans; Male; Sacrococcygeal Region
PubMed: 26651556
DOI: No ID Found -
Neuro-oncology May 2021A prospective 2002-2014 study stratified 160 patients by resection extent and histological grade, reporting results in 2016. We re-analyzed the series after a median of...
Second series by the Italian Association of Pediatric Hematology and Oncology of children and adolescents with intracranial ependymoma: an integrated molecular and clinical characterization with a long-term follow-up.
BACKGROUND
A prospective 2002-2014 study stratified 160 patients by resection extent and histological grade, reporting results in 2016. We re-analyzed the series after a median of 119 months, adding retrospectively patients' molecular features.
METHODS
Follow-up of all patients was updated. DNA copy number analysis and gene-fusion detection could be completed for 94/160 patients, methylation classification for 68.
RESULTS
Progression-free survival (PFS) and overall survival (OS) at 5/10 years were 66/58%, and 80/73%. Ten patients had late relapses (range 66-126 mo), surviving after relapse no longer than those relapsing earlier (0-5 y). On multivariable analysis a better PFS was associated with grade II tumor and complete surgery at diagnosis and/or at radiotherapy; female sex and complete resection showed a positive association with OS. Posterior fossa (PF) tumors scoring ≥0.80 on DNA methylation analysis were classified as PFA (n = 41) and PFB (n = 9). PFB patients had better PFS and OS. Eighteen/32 supratentorial tumors were classified as RELA, and 3 as other molecular entities (anaplastic PXA, LGG MYB, HGNET). RELA had no prognostic impact. Patients with 1q gain or cyclin-dependent kinase inhibitor 2A (CDKN2A) loss had worse outcomes, included significantly more patients >3 years old (P = 0.050) and cases of dissemination at relapse (P = 0.007).
CONCLUSIONS
Previously described prognostic factors were confirmed at 10-year follow-up. Late relapses occurred in 6.2% of patients. Specific molecular features may affect outcome: PFB patients had a very good prognosis; 1q gain and CDKN2A loss were associated with dissemination. To draw reliable conclusions, modern ependymoma trials need to combine diagnostics with molecular risk stratification and long-term follow-up.
Topics: Adolescent; Brain Neoplasms; Child; Child, Preschool; Ependymoma; Female; Follow-Up Studies; Hematology; Humans; Italy; Male; Prognosis; Prospective Studies; Retrospective Studies
PubMed: 33135735
DOI: 10.1093/neuonc/noaa257 -
International Journal of Clinical and... 2012Ependymomas constitute the most common type of primary spinal cord tumors, and are subclassified as myxopapillary ependymoma, classic ependymoma, and anaplastic... (Review)
Review
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.
Topics: Adult; Aged, 80 and over; Biomarkers, Tumor; Cerebellar Neoplasms; Cerebrum; Child, Preschool; Ependymoma; Female; Giant Cells; Humans; Spinal Cord Neoplasms; Treatment Outcome
PubMed: 22808300
DOI: No ID Found -
Acta Neuropathologica Communications Sep 2022Posterior fossa group A ependymomas (EPN_PFA) are characterized by a loss of H3 K27 trimethylation due to either EZHIP overexpression or H3 p.K27M mutation, similar to...
Posterior fossa group A ependymomas (EPN_PFA) are characterized by a loss of H3 K27 trimethylation due to either EZHIP overexpression or H3 p.K27M mutation, similar to H3 K27-altered diffuse midline gliomas (DMG), but in reverse proportions. Very little data is available in the literature concerning H3 K27M-mutant EPN_PFA. Here, we retrospectively studied a series of nine pediatric tumors initially diagnosed as H3 K27M-mutant EPN_PFA to compare them to EZHIP-overexpressing EPN_PFA in terms of radiology, follow-up, histopathology, and molecular biology (including DNA-methylation profiling). Seven tumors clustered within EPN_PFA by DNA-methylation analysis and t-distributed stochastic neighbor embedding. Among the two remaining cases, one was reclassified as a DMG and the last was unclassified. H3 K27M-mutant EPN_PFA cases were significantly older than their counterparts with an EZHIP overexpression. Radiological and histopathological central review of our seven H3 K27M-mutant EPN_PFA cases found them to be similar to their counterparts with an EZHIP overexpression. Sequencing analyses revealed HIST1H3B (n = 2), HIST1H3C (n = 2), H3F3A (n = 1), and HIST1H3D (n = 1) K27M mutations (no sequencing analysis available for the last case which was immunopositive for H3K27M). Consequently, HIST1H3C/D mutations are more frequently observed in EPN_PFA than in classic pontine DMG, H3K27-mutant. Overall survival and event-free survival of EZHIP-overexpressing and H3 K27M-mutant EPN_PFA were similar. After surgery and radiation therapy, 5/7 patients were alive at the end of the follow-up. In summary, the diagnosis of EPN_PFA must include tumor location, growth pattern, Olig2 expression, and DNA-methylation profiling before it can be differentiated from DMG, H3 K27-altered.
Topics: Brain Neoplasms; Child; DNA; Ependymoma; Glioma; Histones; Humans; Radiology; Retrospective Studies
PubMed: 36104744
DOI: 10.1186/s40478-022-01442-4 -
Journal of Neurosurgical Sciences Feb 2018The purpose of this paper was to introduce and review the characteristic imaging features of ependymal neoplasms through a comprehensive case-based approach. Illustrated... (Review)
Review
The purpose of this paper was to introduce and review the characteristic imaging features of ependymal neoplasms through a comprehensive case-based approach. Illustrated cases highlight both common and uncommon manifestations of central nervous system-ependymomas. The combination of imaging features, location of the tumor, and patient's demographics often allow the suggestion of ependymoma as a lead entity in the differential diagnosis. However, significant overlap exists between the radiologic characteristics of ependymomas and those of other tumors commonly encountered in the same locations, which can pose a challenge for a definitive diagnosis based on imaging alone.
Topics: Adult; Central Nervous System Neoplasms; Ependymoma; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Tomography, X-Ray Computed
PubMed: 28945051
DOI: 10.23736/S0390-5616.17.04151-0