scholarly journals Clinicopathological Significance of Nestin Expression as a Diagnostic and Prognostic Marker in Brain Gliomas, Independent of IDH Mutation

2021 ◽  
Author(s):  
Chang Gok Woo
Keyword(s):  
Poor Prognosis ◽  
Tissue Microarrays ◽  
Adult Brain ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Nestin Expression ◽  
High Grade Gliomas ◽  
Health Organization ◽  
Brain Gliomas

Abstract Background: Nestin, a type VI intermediate filament, is expressed in neuroepithelial cells during embryogenesis and has been expressed in various human tumors. Recent studies have reported that expression is associated with poor prognosis in brain tumors, but the results are inconclusive. In this study, we evaluated usefulness of Nestin expression using immunohistochemistry as a diagnostic and prognostic biomarker for IDH mutation and the new World Health Organization (WHO) classification.Methods: To investigate Nestin expression, immunohistochemistry was performed on 92 adult brain gliomas using tissue microarrays. We further analyzed the clinical characteristics and survival outcomes according to Nestin expression and examined its correlation with another glioma biomarker, IDH mutation.Results: Sixty patients (65.2%) were Nestin-positive (weak and strong). Nestin expression and intensity were significantly correlated with age, location, diagnosis, and IDH mutations. Old age and high-grade gliomas showed a higher frequency and stronger intensity of Nestin expression than those of young age and with low-grade gliomas (p<0.001). Gliomas with IDH mutations that are located in the frontal lobe showed no expression or had weak positivity. Multivariate analysis demonstrated that Nestin expression (weak, hazard ratio [HR] 5.39, p=0.036; strong, HR 8.43, p=0.007) and IDH wildtype (HR 7.63; p=.001) were significant independent prognostic factors. Moreover, patients with tumors expressing Nestin showed shorter survival (p<0.001).Conclusions: Nestin expression exhibits high intensity in high-grade gliomas and is a useful diagnostic marker. High expression and level of Nestin were significantly correlated with worse survival and was considered a significant marker of poor prognosis in new WHO classification, independent of IDH mutation.

scholarly journals T2 mapping of the peritumoral infiltration zone of glioblastoma and anaplastic astrocytoma

2021 ◽  
pp. 197140092198932
Author(s):  
Timo Alexander Auer ◽  
Maike Kern ◽  
Uli Fehrenbach ◽  
Yasemin Tanyldizi ◽  
Martin Misch ◽  
...  
Keyword(s):  
Relaxation Time ◽  
Isocitrate Dehydrogenase ◽  
Anaplastic Astrocytoma ◽  
T2 Mapping ◽  
Relaxation Times ◽  
Region Of Interest ◽  
World Health ◽  
High Grade ◽  
High Grade Gliomas ◽  
Health Organization

Purpose To characterise peritumoral zones in glioblastoma and anaplastic astrocytoma evaluating T2 values using T2 mapping sequences. Materials and methods In this study, 41 patients with histopathologically confirmed World Health Organization high grade gliomas and preoperative magnetic resonance imaging examinations were retrospectively identified and enrolled. High grade gliomas were differentiated: (a) by grade, glioblastoma versus anaplastic astrocytoma; and (b) by isocitrate dehydrogenase mutational state, mutated versus wildtype. T2 map relaxation times were assessed from the tumour centre to peritumoral zones by means of a region of interest and calculated pixelwise by using a fit model. Results Significant differences between T2 values evaluated from the tumour centre to the peritumoral zone were found between glioblastoma and anaplastic astrocytoma, showing a higher decrease in signal intensity (T2 value) from tumour centre to periphery for glioblastoma ( P = 0.0049 – fit-model: glioblastoma –25.02± 19.89 (–54–10); anaplastic astrocytoma –5.57±22.94 (–51–47)). Similar results were found when the cohort was subdivided by their isocitrate dehydrogenase profile, showing an increased drawdown from tumour centre to periphery for wildtype in comparison to mutated isocitrate dehydrogenase ( P = 0.0430 – fit model: isocitrate dehydrogenase wildtype –10.35±16.20 (–51) – 0; isocitrate dehydrogenase mutated 12.14±21.24 (–15–47)). A strong statistical proof for both subgroup analyses ( P = 0.9987 – glioblastoma R2 0.93±0.08; anaplastic astrocytoma R2 0.94±0.15) was found. Conclusion Peritumoral T2 mapping relaxation time tissue behaviour of glioblastoma differs from anaplastic astrocytoma. Significant differences in T2 values, using T2 mapping relaxation time, were found between glioblastoma and anaplastic astrocytoma, capturing the tumour centre to the peritumoral zone. A similar curve progression from tumour centre to peritumoral zone was found for isocitrate dehydrogenase wildtype high grade gliomas in comparison to isocitrate dehydrogenase mutated high grade gliomas. This finding is in accordance with the biologically more aggressive behaviour of isocitrate dehydrogenase wildtype in comparison to isocitrate dehydrogenase mutated high grade gliomas. These results emphasize the potential of mapping techniques to reflect the tissue composition of high grade gliomas.

scholarly journals Genetic Abnormalities, Clonal Evolution, and Cancer Stem Cells of Brain Tumors

2018 ◽  
Vol 6 (4) ◽  
pp. 85 ◽  
Author(s):  
Ugo Testa ◽  
Germana Castelli ◽  
Elvira Pelosi
Keyword(s):  
Brain Tumors ◽  
Clonal Evolution ◽  
Pediatric Brain Tumors ◽  
Genetic Alterations ◽  
World Health ◽  
Driver Mutations ◽  
Low Grade ◽  
High Grade ◽  
Genetic Profiling ◽  
Health Organization

Brain tumors are highly heterogeneous and have been classified by the World Health Organization in various histological and molecular subtypes. Gliomas have been classified as ranging from low-grade astrocytomas and oligodendrogliomas to high-grade astrocytomas or glioblastomas. These tumors are characterized by a peculiar pattern of genetic alterations. Pediatric high-grade gliomas are histologically indistinguishable from adult glioblastomas, but they are considered distinct from adult glioblastomas because they possess a different spectrum of driver mutations (genes encoding histones H3.3 and H3.1). Medulloblastomas, the most frequent pediatric brain tumors, are considered to be of embryonic derivation and are currently subdivided into distinct subgroups depending on histological features and genetic profiling. There is emerging evidence that brain tumors are maintained by a special neural or glial stem cell-like population that self-renews and gives rise to differentiated progeny. In many instances, the prognosis of the majority of brain tumors remains negative and there is hope that the new acquisition of information on the molecular and cellular bases of these tumors will be translated in the development of new, more active treatments.

Correlation of Ki-67 and p53 With the New World Health Organization/International Society of Urological Pathology Classification System for Urothelial Neoplasia

2001 ◽  
Vol 125 (5) ◽  
pp. 646-651 ◽  
Author(s):  
Stephen J. Cina ◽  
Kristen J. Lancaster-Weiss ◽  
Kristen Lecksell ◽  
Jonathan I. Epstein
Keyword(s):  
Papillary Carcinoma ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Papillary Lesions ◽  
Flat Lesions ◽  
Papillary Hyperplasia ◽  
Health Organization ◽  
Papillary Neoplasm

Abstract Objective.—The present study examines p53 and Ki-67 staining patterns of the diagnostic entities included within the new World Health Organization/International Society of Urological Pathology (WHO/ISUP) classification of urothelial neoplasms. Design.—We retrospectively studied 151 bladder biopsies from 81 patients with the following neoplasms: normal urothelium (n = 34 biopsies); low-grade intraurothelial neoplasia (LGIUN; n = 19); high-grade intraurothelial neoplasia (HGIUN; n = 20); papillary hyperplasia (n = 4); papilloma (n = 3); papillary neoplasm of low malignant potential (LMP; n = 12); low-grade papillary carcinoma (n = 28); and high-grade papillary carcinoma (n = 31). Sections were labeled immunohistochemically with antibodies to p53 and Ki-67 (MIB-1). Two hundred cells from each lesion were visually counted, and the percentage of positive cells was tabulated without knowledge of the WHO/ISUP diagnosis. Results.—In flat lesions, p53 positivity was of limited diagnostic utility; the marker was present in 6 of 34 benign biopsies, 6 of 19 LGIUNs, and 10 of 20 HGIUNs. In one case in which HGIUN was present elsewhere in the bladder, 29% of the benign urothelial cells were p53 positive. In papillary lesions, p53 positivity was not seen in 4 of 4 cases of papillary hyperplasia, 3 of 3 papillomas, and 8 of 12 LMP tumors. In contrast, p53 was detected in 18 of 28 low-grade and 26 of 31 high-grade papillary urothelial carcinomas. A p53 labeling index (LI) greater than 30% was only seen in HGIUNs and high-grade papillary carcinomas. In flat lesions, an increased Ki-67 LI separated out benign urothelium (mean LI, 0.62%) from dysplasia (mean LI, 3.3%) and HGIUN (mean LI, 11.6%). In papillary lesions, Ki-67 positivity was as follows: papillary hyperplasia (mean LI, 1.1%); papilloma (mean LI, 4.3%); LMP tumors (mean LI, 2.5%), low-grade papillary carcinoma (mean LI, 7.3%); and high-grade carcinoma (mean LI, 15.7%). A Ki-67 LI greater than 10% was seen only in low- and high-grade papillary carcinomas, HGIUN, and single cases of LGIUN and papillary neoplasm of LMP. Conclusions.—An increased proliferative index as demonstrated by immunohistochemical staining for Ki-67 (MIB-1) is most often seen in papillary carcinoma and HGIUN. Marked p53 positivity is also characteristic of carcinoma but may be seen in benign-appearing urothelium, suggesting a “field effect” with occult molecular aberration.

scholarly journals Arterial spin labeling in the grading of brain gliomas: could it help?

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Ahmed A. ElBeheiry ◽  
Doaa M. Emara ◽  
Amany Abdel-Bary Abdel-Latif ◽  
Mohamed Abbas ◽  
Amal S. Ismail
Keyword(s):  
Perfusion Imaging ◽  
Arterial Spin Labeling ◽  
Spin Labeling ◽  
High Morbidity ◽  
Low Grade ◽  
Dynamic Susceptibility ◽  
High Grade ◽  
Low Grade Gliomas ◽  
High Grade Gliomas ◽  
Brain Gliomas

Abstract Background Gliomas are characterized by high morbidity and mortality with low cure and high recurrence rates, which depends to a great degree on the angiogenesis of the tumor. Assessment of such angiogenesis by perfusion techniques is of utmost importance for the preoperative grading of gliomas. The purpose of this study was to assess the role of arterial spin labeling (ASL) perfusion as a non-contrast MRI technique in the grading of brain gliomas, in correlation with the dynamic susceptibility contrast perfusion imaging (DSC-PI). The study was carried out on 35 patients admitted to the Neurosurgery Department with MRI features of gliomas and sent for further perfusion imaging. Non-contrast ASL followed by DSC-PI was done for all cases. The final diagnosis of the cases was established by histopathology. Results Fourteen patients (14/35) had low-grade gliomas while twenty-one (21/35) had high-grade gliomas. In low-grade gliomas, four cases out of 14 were falsely graded as high-grade tumors showing hyperperfusion on ASL, three of which showed DSC-PI hypoperfusion. In high-grade gliomas, two cases out of 21 were interpreted as an indeterminate grade by ASL showing isoperfusion, however showed hyperperfusion on DSC-PI. ROC curve analysis showed ASL-derived rCBF > 2.08 to have 80.95% sensitivity, 85.71% specificity, and overall accuracy of 82.86% compared to 100% sensitivity, specificity, and accuracy of DSC-PI-derived rCBV and rCBF of > 1.1 and > 0.9, respectively. A significant positive correlation was noted between ASL and DSC-PI with correlation coefficient reaching r = 0.80 between ASL-rCBF and DSC-rCBF (p < 0.01) and r = 0.68 between ASL and DSC-rCBV (p < 0.01). Conclusions ASL is a relatively recent non-contrast perfusion technique that obtains results which are in fair agreement with the more established DSC perfusion imaging making it an alternative method for preoperative assessment of perfusion of gliomas, especially for patients with contraindications to contrast agents.

scholarly journals Expression of Ki-67 in Low-Grade and High-Grade Astrocytomas

2018 ◽  
Vol 27 (3) ◽  
pp. 225-230
Author(s):  
Cléciton Braga Tavares ◽  
Francisca Das Chagas Sheyla Almeida Gomes Braga ◽  
Emerson Brandão Sousa ◽  
José Nazareno Pearce de Oliveira Brito
Keyword(s):  
Survival Time ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Exclusion Criteria ◽  
World Health Organization Classification ◽  
Ki 67 ◽  
Mesh Terms ◽  
Health Organization ◽  
Selection Of

Objective. This review aims to carry out a survey on the importance of Ki67 in the astrocytomas study. Methods. A search in the electronic database of Medline via PubMed and using MESH terms was carried out. Articles were published between January 2005 and December 2015. All studies were analyzed by two experienced researchers, using inclusion and exclusion criteria for the selection of studies. Results. Five studies showed an association between cell proliferation and survival time. Four articles mentioned as cut-off point for survival a Ki67 of 10% and a fifth article a Ki67 of 14.3. A study showed an association between therapeutic failure and Ki67. Four studies have made the association between Ki67 and World Health Organization classification. Conclusion. High levels of Ki67 are associated to high grade astrocytomas and lower survival time.

Low-Grade Papillary Urothelial Carcinoma of the Urinary Bladder: A Clinicopathologic Analysis of a Post–World Health Organization/International Society of Urological Pathology Classification Cohort From a Single Academic Center

2010 ◽  
Vol 134 (8) ◽  
pp. 1160-1163
Author(s):  
Hiroshi Miyamoto ◽  
Fadi Brimo ◽  
Luciana Schultz ◽  
Huihui Ye ◽  
Jeremy S. Miller ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
World Health Organization ◽  
International Society ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
The Mean ◽  
Papillary Urothelial Carcinoma ◽  
Health Organization ◽  
Grade Progression

Abstract Context.—Few large cohort studies have addressed outcome in patients with noninvasive low-grade papillary urothelial carcinoma (LG-UrCa) following implementation of the 2004 World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification. Objective.—To evaluate our cohort of LG-UrCa cases classified according to 2004 WHO/ISUP to reassess outcome and interobserver agreement. Design.—Files were searched for all patients diagnosed with LG-UrCa between 1998 and 2008. All sections were reevaluated for accuracy of classification. Results.—A total of 112 cases initially diagnosed as LG-UrCa were identified. Of those, 8 of 55 cases (15%) initially diagnosed by nonurologic pathologists were reclassified as high-grade papillary urothelial carcinoma and were excluded. The mean length of follow-up was 40.1 months (range, 2–113 months). Tumor recurrence was encountered in 56 of 104 patients (53.8%), including 37 (35.6%) with LG-UrCa or lower-grade tumors and 19 (18.3%) with high-grade papillary urothelial carcinoma. Of the 19 patients demonstrating grade progression, 7 (37%) also developed stage progression (invasive carcinoma, n  =  5; metastatic carcinoma, n  =  2). Seven patients eventually underwent radical cystectomy. None of the 104 patients died of bladder cancer. The mean number of recurrence episodes was 3.11. The mean durations of time to first recurrence and time to grade progression were 13.9 months and 25.1 months, respectively. The mean size of initial tumors was 1.73 cm. There was no significant correlation between tumor size, patient age, sex, or smoking history and the likelihood for recurrence or grade progression. A significantly higher rate of recurrence was seen in patients with multiple tumors at initial diagnosis (P  =  .04). Conclusions.—A tendency to underdiagnose high-grade papillary urothelial carcinoma continues to exist. More than half (53.8%) of patients with LG-UrCa developed recurrence, with an 18.3% incidence of grade progression and a 6.7% incidence of stage progression. Patients with multiple initial tumors had significantly higher risk of developing recurrence.

scholarly journals Insular glioma surgery: an evolution of thought and practice

2019 ◽  
Vol 130 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Shawn L. Hervey-Jumper ◽  
Mitchel S. Berger
Keyword(s):  
Internal Capsule ◽  
World Health ◽  
Surgical Approaches ◽  
High Grade ◽  
Glioma Surgery ◽  
Lenticulostriate Arteries ◽  
History Of ◽  
High Grade Gliomas ◽  
Cortical Regions ◽  
Health Organization

OBJECTIVEThe goal of this article is to review the history of surgery for low- and high-grade gliomas located within the insula with particular focus on microsurgical technique, anatomical considerations, survival, and postoperative morbidity.METHODSThe authors reviewed the literature for published reports focused on insular region anatomy, neurophysiology, surgical approaches, and outcomes for adults with World Health Organization grade II–IV gliomas.RESULTSWhile originally considered to pose too great a risk, insular glioma surgery can be performed safely due to the collective efforts of many individuals. Similar to resection of gliomas located within other cortical regions, maximal resection of gliomas within the insula offers patients greater survival time and superior seizure control for both newly diagnosed and recurrent tumors in this region. The identification and the preservation of M2 perforating and lateral lenticulostriate arteries are critical steps to preventing internal capsule stroke and hemiparesis. The transcortical approach and intraoperative mapping are useful tools to maximize safety.CONCLUSIONSThe insula’s proximity to middle cerebral and lenticulostriate arteries, primary motor areas, and perisylvian language areas makes accessing and resecting gliomas in this region challenging. Maximal safe resection of insular gliomas not only is possible but also is associated with excellent outcomes and should be considered for all patients with low- and high-grade gliomas in this area.

Gliosarcoma – Clinico-pathology, Genetics and a Review of Rare Congenital Cases

2009 ◽  
Vol 05 (01) ◽  
pp. 20
Author(s):  
Christopher Dunham ◽  
Keyword(s):  
World Health Organization ◽  
Brain Tumours ◽  
Poor Prognosis ◽  
Genetic Data ◽  
World Health ◽  
Recent Analysis ◽  
Molecular Profile ◽  
Low Grade ◽  
Who Grade ◽  
Health Organization

Congenital brain tumours are rare. In general, they are preferentially located in the supratentorial compartment, and despite the occurrence of low-grade entities, these tumours are associated with a very poor prognosis. When strictly defined, the most common forms of congenital neoplasia are teratomas and astrocytomas. Among the astrocytomas, all grades (World Health Organization [WHO] I–IV) and many of the different subtypes are represented. This includes the most prognostically worrisome ‘diffusely infiltrating’ astrocytomas. Gliosarcomas are a variant of glioblastoma (i.e. WHO grade IV astrocytoma) that exhibits both malignant astrocytic (i.e. glioblastoma) and mesenchymal (i.e. sarcoma) components. Despite their bi-phasic histology, genetic analyses of adult gliosarcoma cases suggest not only a molecular profile similar to glioblastoma, but also a monoclonal histogenesis for the glial and sarcomatous elements. Congenital gliosarcomas are extremely rare, with only a handful of cases being described in the literature. Not surprisingly, therefore, detailed clinical, pathological and genetic data are limited. However, based on a recent analysis of congenital glioblastomas, congenital gliosarcomas may constitute an entity that is genetically and prognostically distinct from adult cases.

scholarly journals The Challenges of Management of High-grade Gliomas in Nigeria

2017 ◽  
Vol 08 (03) ◽  
pp. 407-411 ◽  
Author(s):  
Chika Anele Ndubuisi ◽  
Wilfred C. Mezue ◽  
Martin Nzegwu ◽  
Okwuoma Okwunodulu ◽  
Gabriel Ejembi ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Adjuvant Treatment ◽  
Tumor Volume ◽  
Extent Of Resection ◽  
World Health ◽  
High Grade ◽  
Karnofsky Score ◽  
Recorded Data ◽  
High Grade Gliomas ◽  
Health Organization

ABSTRACT Background: High-grade gliomas (HGG) are among the most challenging brain tumors despite many research efforts worldwide. Aim: The aim of this study was to evaluate the local challenges that may influence outcome of HGG managed in a neurosurgical center in Nigeria. Methodology: Retrospective analysis of prospectively recorded data of patients managed for intracranial HGG at Memfys Hospital for Neurosurgery, Enugu, Nigeria, between the year 2006 and 2015. Only cases with conclusive histology following surgery were analyzed. Results: Glioma was 60 (23.8%) of 252 histology confirmed brain tumors. HGG represented 53.8% of gliomas with male:female ratio of 2.2:1.0 and peaked from fifth decade of life. Glioblastoma multiforme accounted for 69% of HGG. At 1-year postsurgery, 53% of HGGs were dead and 88% of these deaths were in the World Health Organization Grade IV group. Only 40% of cases could receive adjuvant treatment with only 15% mortality at 1 year in this subgroup that received adjuvant therapy. In addition, 19% of cases had surgery at Karnofsky score (Ks) of ≤70%. However, 94% of mortality at 1 year was related to surgery at Ks of ≤60%. Only four patients had a tumor volume of ≤50 cm3, and among these cases, three patients were independent at 1 year. Patients with tumor volume above 50 cm3 accounted for 94% of mortality. Conclusion: The peak age incidence for HGG seems to be lower than in Caucasians. Most cases present late with poor Ks and big tumor volume. The proportion with access to adjuvant treatment is still poor. Preoperative Karnofsky, extent of resection, duration of hospital, and Intensive Care Unit stay have impact on outcome.

scholarly journals Survival and low-grade glioma: the emergence of genetic information

2015 ◽  
Vol 38 (1) ◽  
pp. E6 ◽  
Author(s):  
Elizabeth B. Claus ◽  
Kyle M. Walsh ◽  
John K. Wiencke ◽  
Annette M. Molinaro ◽  
Joseph L. Wiemels ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Young Patients ◽  
High Grade Glioma ◽  
The United States ◽  
Low Grade Glioma ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Who Grade ◽  
Health Organization

Significant gaps exist in our understanding of the causes and clinical management of glioma. One of the biggest gaps is how best to manage low-grade (World Health Organization [WHO] Grade II) glioma. Low-grade glioma (LGG) is a uniformly fatal disease of young adults (mean age 41 years), with survival averaging approximately 7 years. Although LGG patients have better survival than patients with high-grade (WHO Grade III or IV) glioma, all LGGs eventually progress to high-grade glioma and death. Data from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute suggest that for the majority of LGG patients, overall survival has not significantly improved over the past 3 decades, highlighting the need for intensified study of this tumor. Recently published research suggests that historically used clinical variables are not sufficient (and are likely inferior) prognostic and predictive indicators relative to information provided by recently discovered tumor markers (e.g., 1p/19q deletion and IDH1 or IDH2 mutation status), tumor expression profiles (e.g., the proneural profile) and/or constitutive genotype (e.g., rs55705857 on 8q24.21). Discovery of such tumor and constitutive variation may identify variables needed to improve randomization in clinical trials as well as identify patients more sensitive to current treatments and targets for improved treatment in the future. This article reports on survival trends for patients diagnosed with LGG within the United States from 1973 through 2011 and reviews the emerging role of tumor and constitutive genetics in refining risk stratification, defining targeted therapy, and improving survival for this group of relatively young patients.

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