-
Veterinary Pathology Sep 2021Gliomas are relatively common tumors in aged dogs (especially brachycephalic breeds), and the dog is proving to be useful as a translational model for humans with brain...
Gliomas are relatively common tumors in aged dogs (especially brachycephalic breeds), and the dog is proving to be useful as a translational model for humans with brain tumors. Hitherto, there is relatively little prognostic data for canine gliomas and none on outcome related to specific histological features. Histologic sections of tumor biopsies from 33 dogs with glioma treated with surgical resection and immunotherapy and 21 whole brains obtained postmortem were reviewed. Tumors were diagnosed as astrocytic, oligodendroglial, or undefined glioma using Comparative Brain Tumor Consortium criteria. Putative features of malignancy were evaluated, namely, mitotic counts, glomeruloid vascularization, and necrosis. For biopsies, dogs with astrocytic tumors lived longer than those with oligodendroglial or undefined tumor types (median survival 743, 205, and 144 days, respectively). Dogs with low-grade gliomas lived longer than those with high-grade gliomas (median survival 734 and 194 days, respectively). Based on analysis of tumor biopsies, low mitotic counts, absence of glomeruloid vascularization, and absence of necrosis correlated with increased survival (median 293, 223, and 220 days, respectively), whereas high mitotic counts, glomeruloid vascularization, and necrosis correlated with poor survival (median 190, 170, and 154 days, respectively). Mitotic count was the only histological feature in biopsy samples that significantly correlated with survival ( < .05). Whole-brain analyses for those same histologic features had similar and more robust correlations, and were statistically significant for all features ( < .05). The small size of biopsy samples may explain differences between biopsy and whole-brain tumor data. These findings will allow more accurate prognosis for gliomas.
Topics: Animals; Astrocytoma; Brain Neoplasms; Dog Diseases; Dogs; Glioma; Prognosis; Retrospective Studies
PubMed: 34219560
DOI: 10.1177/03009858211025795 -
Folia Neuropathologica 2021This study has assessed the diagnostic ability of oligodendrocyte-2 (Olig2), CD99, and epithelial membrane antigen (EMA) immunohistochemical stains to diagnose...
INTRODUCTION
This study has assessed the diagnostic ability of oligodendrocyte-2 (Olig2), CD99, and epithelial membrane antigen (EMA) immunohistochemical stains to diagnose oligodendroglial-like neoplasms as central neurocytoma, ependymoma, or oligodendroglioma.
MATERIAL AND METHODS
An immunohistochemistry (IHC) panel of Olig2, EMA, and CD99 was performed on 18 central neurocytomas, 46 ependymomas, and 28 oligodendrogliomas. A quantitative labelling index of stained tumor cells was assessed using a scoring system, and its diagnostic predictability was evaluated with multinomial logistic regression.
RESULTS
Significant differences in IHC expression patterns were observed between all tumor groups (p < 0.001). The labeling indices of the histochemical expression of Olig2, EMA, and CD99 were related to diagnostic predictability. Olig2 was unlikely to differentiate ependymoma from central neurocytoma (p = 0.154), while EMA and CD99 were significant in diagnosing these two tumors (p < 0.05). Olig2 was a specific marker of oligodendroglioma, differentiating it from ependymoma and central neurocytoma (p 0.05), but CD99 significantly differentiated ependymoma from oligodendroglioma (p = 0.022). These labelling indices were used to re-assess the diagnostic accuracy, regardless of tumor location and histology, and yielded significantly different tumor diagnoses.
CONCLUSIONS
The IHC panel of Olig2, EMA, and CD99 should be used to differentiate oligodendroglial-like neoplasms. Olig2 is a specific IHC marker to diagnose oligodendroglioma and differentiate it from ependymoma and central neurocytoma. Lack of Olig2 expression rules out oligodendroglioma and suggests the diagnosis of ependymoma rather than central neurocytoma if the EMA labelling index shows diffuse/partial expression. CD99 is considered a sensitive marker for ependymoma but not central neurocytoma.
Topics: 12E7 Antigen; Biomarkers, Tumor; Brain Neoplasms; Ependymoma; Humans; Mucin-1; Neurocytoma; Oligodendrocyte Transcription Factor 2; Oligodendroglia; Oligodendroglioma
PubMed: 34628794
DOI: 10.5114/fn.2021.108526 -
Turkish Neurosurgery 2022To evaluate the clinical features, treatment approaches, and outcomes of glial tumors in children.
AIM
To evaluate the clinical features, treatment approaches, and outcomes of glial tumors in children.
MATERIAL AND METHODS
Files (2006 to 2020) of children diagnosed with glial tumors and followed-up were reviewed retrospectively. Information regarding demographic and clinical characteristics, treatment approaches, and outcomes were retrieved from the patients? files.
RESULTS
Of the total of 180 pediatric patients diagnosed with brain tumors, 73 (40.6%) had glial tumors. The children with astrocytoma were in the age range of 2?18 years (median age: 8.7 years), while the ages of children with ependymoma ranged from three months to 10 years (median age: 3 years). This difference was statistically significant (p < 0.0001). The male to female ratio was 1.6. The most common symptoms or signs were headaches (n=34, 46.6%), abnormal gait or coordination (n=22, 30.2%), vomiting (n=21, 28.8%), and cranial nerve palsies (n=20, 27.4%). The pathological diagnoses were astrocytomas (n=53, 72.6%), oligodendroglial tumors (n=2, 2.7%), ependymoma (n=15, 20.7%), and other glial tumors (n=3, 4.1%). The most common tumor location was supratentorial (n=42, 57.5%), while midline glioma was detected in seven patients. The 5-year overall survival (OS) rate of all glial tumors, astrocytoma, and ependymoma was 42%, 40%, and 55%, respectively. The 5-year OS rate of the tumor Grade I, II, III, and IV was 77.2%, 45%, 32%, and 0%, respectively (p < 0.0001). The 5-year OS rate of supratentorial, infratentorial, and spinal tumors was 25.6%, 63.6%, and 50%, respectively (p=0.021). In Cox regression analysis, it was found that the tumor resection and grade had an effect on the tumor prognosis.
CONCLUSION
Treatment results are not satisfactory in high-grade astrocytomas. There is a need for new treatment approaches that would take cognizance of molecular features and adopt multidisciplinary approaches.
Topics: Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Ependymoma; Female; Glioma; Humans; Infant; Male; Prognosis; Retrospective Studies; Treatment Outcome
PubMed: 34751424
DOI: 10.5137/1019-5149.JTN.34801-21.2 -
Ideggyogyaszati Szemle Sep 2021Aberrant activation of the Wnt pathway contributes to differentiation and maintenance of cancer stem cells underlying gliomagenesis. The aim of our research was to...
BACKGROUND AND PURPOSE
Aberrant activation of the Wnt pathway contributes to differentiation and maintenance of cancer stem cells underlying gliomagenesis. The aim of our research was to determine as to what degrees some Wnt markers are expressed in gliomas of different grades, lineages and molecular subtypes.
METHODS
Nine grade II, 10 grade III and 72 grade IV surgically removed, formalin-fixed paraffin-embedded glioma specimens were included. Mutation status of IDH1 codon 132 was defined by immunohistochemistry and pyrosequencing in all tumors. Grade II and III astrocytic and oligodendroglial tumors were further tested for the expression of p53 and ATRX by immunohistochemistry, and codeletion of 1p19q by fluorescent in situ hybridization. Expression levels of the non-canonical Wnt5a and Fzd2, and the canonical Wnt3a and beta-catenin Wnt pathway markers were determined by immunohistochemistry, and compared between subgroups stratified according to grade, lineage and the presence or absence of IDH1 R132H/C mutations.
RESULTS
In the normal brain - grade II-IV glioma comparisons, a gradual increase was observed for the expressions of Wnt5a, Wnt3a, Fzd2 and beta-catenin. In the astroglial and oligodendroglial lineages of grade II and III gliomas, only the Wnt5a expression was significantly higher in the astroglial subgroup. Stratification according to the IDH1 status resulted in a significant increase of the Wnt3 expression in the wild type grade II-IV gliomas.
CONCLUSION
These data extend previous observations and show a correlation of Wnt pathway activity with glioma grade. Further investigations of the Wnt marker expression regulation according to glioma lineage or IDH gene mutational status are in progress by using more exact molecular approaches.
Topics: Brain Neoplasms; Glioma; Humans; In Situ Hybridization, Fluorescence; Isocitrate Dehydrogenase; Wnt Signaling Pathway
PubMed: 34657400
DOI: 10.18071/isz.74.0349 -
Neuro-oncology Nov 2019We identify cognitive impairment and MRI structural brain changes in long-term oligodendroglial tumor survivors treated with radiation therapy (RT) alone (21%) or with...
BACKGROUND
We identify cognitive impairment and MRI structural brain changes in long-term oligodendroglial tumor survivors treated with radiation therapy (RT) alone (21%) or with chemotherapy (CT) (79%).
METHODS
Oligodendroglial tumor patients (based on the World Health Organization [WHO] 2007 classification) who completed RT ± CT at least 2 years before the study initiation, were classified into 3 groups according to the time treatment was completed: Group 1 = 2-5 years (n = 22), Group 2 = 6-10 years (n = 13), and Group 3 >10 years (n = 13). All patients had a cross-sectional neuropsychological evaluation (n = 48) and a longitudinal volumetric analysis (gray matter [GM; n = 34]) between postsurgical and last follow-up MRI. White matter (WM) changes on MRI were assessed using a qualitative scale.
RESULTS
There were no differences regarding tumor or treatment-related characteristics between groups. Six of 22 patients (27.3%) in Group 1; 5/13 (38.5%) in Group 2; and 9/13 (69.2%) in Group 3 had cognitive impairment that was considered severe in 3/22 patients (13.6%) in Group 1; 4/13 (30.8%) in Group 2; and 6/13 (46.2%) in Group 3. Patients in Groups 2 and 3 showed significant GM atrophy and more leukoencephalopathy than Group 1. Cognitive deficits were associated with brain atrophy and WM changes.
CONCLUSIONS
Long-term oligodendroglial tumor survivors who underwent standard RT ± CT treatment, mainly >5 years of its completion, present cognitive impairment, especially on memory and executive functions, associated with late GM and WM damage, thus highlighting the need of developing future strategies in patients with oligodendroglial tumor and long expected survival.
Topics: Adult; Aged; Cancer Survivors; Chemoradiotherapy; Cognition Disorders; Cross-Sectional Studies; Female; Follow-Up Studies; Gray Matter; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Oligodendroglioma; Prognosis; Retrospective Studies; Survival Rate; White Matter; Young Adult
PubMed: 31549152
DOI: 10.1093/neuonc/noz130 -
AJNR. American Journal of Neuroradiology Nov 2022Despite advances in molecular imaging, preoperative diagnosis of astrocytomas and oligodendrogliomas can be challenging. In the present study, we assessed whether 7T SWI...
BACKGROUND AND PURPOSE
Despite advances in molecular imaging, preoperative diagnosis of astrocytomas and oligodendrogliomas can be challenging. In the present study, we assessed whether 7T SWI can be used to distinguish astrocytomas and oligodendrogliomas and whether malignant grading of gliomas is possible.
MATERIALS AND METHODS
7T SWI was performed on 21 patients with gliomas before surgery with optimization for sharp visualization of the corticomedullary junction. Scoring for cortical thickening and displacement of medullary vessels, characteristic of oligodendroglial tumors, and cortical tapering, characteristic of astrocytic tumors, was performed. Additionally, characteristics of malignancy, including thickening of the medullary veins, the presence of microbleeds, and/or necrosis were scored.
RESULTS
Scoring for oligodendroglial (highest possible score, +3) and astrocytic (lowest score possible, -3) characteristics yielded a significant difference between astrocytomas and oligodendrogliomas (mean, -1.93 versus +1.71, < .01). Scoring for malignancy was significantly different among the World Health Organization grade II ( = 10), grade III ( = 4), and grade IV ( = 7) tumors (mean, 0.20 versus 1.38 versus 2.79). Cortical thickening was observed significantly more frequently in oligodendrogliomas ( < .02), with a sensitivity of 71.4% and specificity of 85.7%; observation of tapering of the cortex was higher in astrocytomas ( < .01) with a sensitivity of 85.7% and specificity of 100%.
CONCLUSIONS
Visualization of the corticomedullary junction by 7T SWI was useful in distinguishing astrocytomas and oligodendrogliomas. Observation of tapering of the cortex was most sensitive and specific for diagnosing astrocytomas. Reliably predicting malignant grade was also possible by 7T SWI.
Topics: Humans; Oligodendroglioma; Brain Neoplasms; Astrocytoma; Glioma; Magnetic Resonance Imaging
PubMed: 36229164
DOI: 10.3174/ajnr.A7666 -
Journal of Cancer Research and... 2023Gliomas are the most common primary intracranial tumors. The current World Health Organization (WHO) classification of central nervous system tumors recommends...
INTRODUCTION
Gliomas are the most common primary intracranial tumors. The current World Health Organization (WHO) classification of central nervous system tumors recommends integrated histo-molecular diagnosis of gliomas. However, molecular testing is not available in even most of the advanced centers of our country, and histopathology aided with immunohistochemistry (IHC) is still widely used for diagnosis. Immunohistochemical markers such as iso-citrate dehydrogenase1 (IDH1) and Alpha Thalassemia/Mental Retardation Syndrome X-linked (ATRX) can be reliably used for the correct diagnosis, prognosis, and treatment of gliomas.
AIM
We aimed to develop a diagnostic algorithm by integrating morphology, IDH1, and ATRX status of gliomas seen in our institute for 1 year.
SETTINGS AND DESIGN
Analytical cross-sectional study.
MATERIALS AND METHODS
This study included 60 histopathologically confirmed cases of astrocytic (n = 51) and oligodendroglial tumors (n = 9). Clinical, radiological, and histopathological features were noted and tumor grades assigned according to the WHO recommendations. IDH1 and ATRX mutation status was evaluated using IHC. The tumors were divided into three molecular groups on the basis of their IDH1 and ATRX mutation status: (1) Group 1: IDH1 negative and ATRX positive, (2) Group 2: IDH1 positive and ATRX positive, (3) Group 3: IDH1 positive and ATRX negative.
RESULTS
The mean age of presentation was 45.0 ± 15.8 years with a male-to-female ratio of 2:1. Seizures, headache, and hemiparesis were the most common modes of presentation. The tumor subtypes studied were glioblastoma (n = 32), anaplastic astrocytoma (n = 7), diffuse astrocytoma (n = 6), oligodendroglioma (n = 6), pilocytic astrocytoma (n = 6), and anaplastic oligodendroglioma (n = 3). IDH1 mutation was present in 26 cases including anaplastic astrocytoma (n = 7), diffuse astrocytoma (n = 6), oligodendroglioma (n = 5), secondary glioblastoma (n = 5), and anaplastic oligodendroglioma (n = 3). ATRX mutation, i. e., loss of ATRX was observed in 17 cases including diffuse astrocytoma (n = 5), anaplastic astocytoma (n = 5), anaplastic oligodendroglioma (n = 3), oligodendroglioma (n = 3), and secondary glioblastoma (n = 1). All six cases of pilocytic astrocytoma were negative for IDH1 and ATRX mutation. There were 34 patients in Group 1 (IDH1- and ATRX +), nine cases in Group 2 (IDH1 + and ATRX +), and 17 patients in Group 3 (IDH1 + and ATRX-).
CONCLUSION
Diagnosis of gliomas should be based on a detailed clinicoradiological and histopathological assessment, followed by genotypic characterization. Evaluation for IDH1and ATRX status has both diagnostic and prognostic value as it helps in differentiating gliomas from reactive gliosis, primary glioblastoma from secondary glioblastoma, and pilocytic astrocytoma (WHO grade I) from diffuse astrocytoma (WHO grade II). Tumors with IDH1 mutations have a better outcome than those with wild-type IDH. IHC can serve as a useful surrogate to conventional molecular tests in resource-constrained settings. By devising an algorithm based on morphological and IHC features, we were able to stratify gliomas into three prognostic subgroups.
Topics: Humans; Male; Female; Adult; Middle Aged; Oligodendroglioma; Glioblastoma; Cross-Sectional Studies; X-linked Nuclear Protein; Glioma; Astrocytoma; Brain Neoplasms; Mutation; Prognosis; Citrates; Citric Acid; Isocitrate Dehydrogenase; Algorithms
PubMed: 37470575
DOI: 10.4103/jcrt.jcrt_102_21 -
Journal of Clinical Oncology : Official... Aug 2022JCO Anaplastic oligodendroglial tumors (AOTs) are chemotherapy-sensitive brain tumors. We report the final very long-term survival results from European Organization...
JCO Anaplastic oligodendroglial tumors (AOTs) are chemotherapy-sensitive brain tumors. We report the final very long-term survival results from European Organization for the Research and Treatment of Cancer 26951 and Radiation Therapy Oncology Group 9402 phase III trials initiated in 1990s, which both studied radiotherapy with/without neo/adjuvant procarbazine, lomustine, and vincristine (PCV) for newly diagnosed anaplastic oligodendroglial tumors. The median follow-up duration in both was 18-19 years. For European Organization for the Research and Treatment of Cancer 26951, median, 14-year, and probable 20-year overall survival rates without versus with PCV were 2.6 years, 13.4%, and 10.1% versus 3.5 years, 25.1%, and 16.8% (N = 368 overall; hazard ratio [HR] 0.78; 95% CI, 0.63 to 0.98; = .033), with 1p19q codeletion 9.3 years, 26.2%, and 13.6% versus 14.2 years, 51.0%, and 37.1% (n = 80; HR 0.60; 95% CI, 0.35 to 1.03; = .063), respectively. For Radiation Therapy Oncology Group 9402, analogous results were 4.8 years, 16.5%, and 11.2% versus 4.8 years, 29.1%, and 24.6% (N = 289 overall; HR 0.79; 95% CI, 0.61 to 1.03; = .08), with codeletion 7.3 years, 25.0%, and 14.9% versus 13.2 years, 46.1%, and 37% (n = 125; HR 0.61; 95% CI, 0.40 to 0.94; = .02), respectively. With that, the studies show similar long-term survival even without tumor recurrence in a significant proportion of patients after first-line treatment with radiotherapy/PCV.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Clinical Trials, Phase III as Topic; Humans; Lomustine; Neoplasm Recurrence, Local; Oligodendroglioma; Procarbazine; Vincristine
PubMed: 35731991
DOI: 10.1200/JCO.21.02543 -
International Journal of Molecular... Nov 2021Malignant brain tumors are responsible for catastrophic morbidity and mortality globally. Among them, glioblastoma multiforme (GBM) bears the worst prognosis. The...
Malignant brain tumors are responsible for catastrophic morbidity and mortality globally. Among them, glioblastoma multiforme (GBM) bears the worst prognosis. The GrpE-like 2 homolog () plays a crucial role in regulating mitochondrial protein import and redox homeostasis. However, the role of in human glioblastoma has yet to be clarified. In this study, we investigated the function of in glioma. Based on bioinformatics analyses from the Cancer Gene Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we inferred that expression positively correlates with WHO tumor grade ( < 0.001), IDH mutation status ( < 0.001), oligodendroglial differentiation ( < 0.001), and overall survival ( < 0.001) in glioma datasets. Functional validation in LN229 and GBM8401 GBM cells showed that knockdown efficiently inhibited cellular proliferation. Moreover, GRPEL2 suppression induced cell cycle arrest at the sub-G1 phase. Furthermore, silencing decreased intracellular reactive oxygen species (ROS) without impending mitochondria membrane potential. The cellular oxidative respiration measured with a Seahorse XFp analyzer exhibited a reduction of the oxygen consumption rate (OCR) in GBM cells by , which subsequently enhanced autophagy and senescence in glioblastoma cells. Taken together, GRPEL2 is a novel redox regulator of mitochondria bioenergetics and a potential target for treating GBM in the future.
Topics: Apoptosis; Brain Neoplasms; Case-Control Studies; Cell Cycle; Cell Proliferation; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Intracellular Signaling Peptides and Proteins; Membrane Potential, Mitochondrial; Mitochondria; Oxidation-Reduction; Prognosis; Protein Transport; Reactive Oxygen Species; Survival Rate; Tumor Cells, Cultured
PubMed: 34884508
DOI: 10.3390/ijms222312705 -
Nature Communications Apr 2022Glioblastoma (GBM) is a deadly disease without effective treatment. Because glioblastoma stem cells (GSCs) contribute to tumor resistance and recurrence, improved...
Glioblastoma (GBM) is a deadly disease without effective treatment. Because glioblastoma stem cells (GSCs) contribute to tumor resistance and recurrence, improved treatment of GBM can be achieved by eliminating GSCs through inducing their differentiation. Prior efforts have been focused on studying GSC differentiation towards the astroglial lineage. However, regulation of GSC differentiation towards the neuronal and oligodendroglial lineages is largely unknown. To identify genes that control GSC differentiation to all three lineages, we performed an image-based genome-wide RNAi screen, in combination with single-cell RNA sequencing, and identified ZNF117 as a major regulator of GSC differentiation. Using patient-derived GSC cultures, we show that ZNF117 controls GSC differentiation towards the oligodendroglial lineage via the Notch pathway. We demonstrate that ZNF117 is a promising target for GSC differentiation therapy through targeted delivery of CRISPR/Cas9 gene-editing nanoparticles. Our study suggests a direction to improve GBM treatment through differentiation of GSCs towards various lineages.
Topics: Brain Neoplasms; Cell Differentiation; Cell Line, Tumor; Glioblastoma; Humans; Neoplastic Stem Cells
PubMed: 35459228
DOI: 10.1038/s41467-022-29884-3