Immunohistochemical Analysis of p18INK4C and p14ARF Protein Expression in 117 Oligodendrogliomas

2002 ◽  
Vol 126 (1) ◽  
pp. 42-48
Author(s):  
Andrey Korshunov ◽  
Andrey Golanov
Keyword(s):  
Clinical Outcome ◽  
Protein Expression ◽  
Color Image ◽  
Tumor Grade ◽  
World Health ◽  
Low Grade ◽  
Image Analyzer ◽  
Survival Times ◽  
Who Grade ◽  
Risk Of Death

Abstract Objective.—To investigate immunoexpression of 2 cyclin-dependent kinase inhibitors, p18INK4C (p18) and p14ARF (p14), in oligodendrogliomas and to evaluate the possible association with tumor grade and clinical outcome. Design.—One hundred seventeen specially selected cases of cerebral oligodendrogliomas were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to p18INK4C (118.2) and p14ARF (FL-132) proteins. A computerized color image analyzer was used to count immunostained nuclei. Results.—p18 nuclear immunoexpression was found in 57 (49%) of the oligodendrogliomas we studied. p18 immunoreactivity exhibited a clear tendency to elevate with increasing tumor grade, and the mean p18 labeling index was 9.7% for low-grade (World Health Organization [WHO] grade II) and 19.2% for high-grade (WHO III) tumors. p14-immunopositive nuclei were found in 87 (74%) tumors, and p14 immunoreactivity showed no correlation with oligodendroglioma histological malignancy. Survival times were significantly reduced for p18-positive tumors, and risk of death was independently associated with p18 expression (hazard ratio = 2.48; P = .01). There was no difference in survival times in patients with or without p14 immunoreactivity. Conclusions.—p18 protein expression is closely associated with malignant oligodendrogliomas and worse clinical outcome. It seems unlikely that p14 immunohistochemistry will be of value in assessing individual prognosis for these tumors.

The Prognostic Significance of DNA Topoisomerase II-alpha (Ki-S1), p21/Cip-1, and p27/Kip-1 Protein Immunoexpression in Oligodendrogliomas

2001 ◽  
Vol 125 (7) ◽  
pp. 892-898 ◽  
Author(s):  
Andrey Korshunov ◽  
Andrey Golanov
Keyword(s):  
Topoisomerase Ii ◽  
World Health ◽  
Low Grade ◽  
Image Analyzer ◽  
High Grade ◽  
Dna Topoisomerase Ii ◽  
Survival Times ◽  
Topoisomerase Ii Alpha ◽  
Dna Topoisomerase ◽  
The Mean

Abstract Objective.—To evaluate a possible association between clinical outcome of patients with oligodendroglioma and expression of 2 cyclin-dependent kinase inhibitors, p21/Cip-1 (p21) and p27/Kip-1 (p27), and of DNA topoisomerase II-alpha (Ki-S1), which has been recently used as a marker of cellular proliferation. Design.—Ninety-one specially selected patients with cerebral oligodendrogliomas treated with surgery and radiotherapy were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to p21, p27, and Ki-S1. A computerized color image analyzer was used to count immunostained nuclei. Results.—The mean Ki-S1 labeling index (LI) was found to be significantly prominent for World Health Organization (WHO) high-grade tumors (9.5% vs 3.2% for WHO low-grade tumors). In contrast, the mean p27 LI was significantly higher for low-grade tumors (43.3% vs 25.7% for high-grade tumors). The number of p21-positive cases and the mean p21 LI were found to be relatively equal for low- and high-grade tumors. For low-grade oligodendrogliomas, the progression-free and overall survival times were found to be significantly shorter for tumors with p27 LIs less than 20%. For high-grade oligodendrogliomas, survival times were significantly reduced for tumors with Ki-S1 LIs greater than 10%. Regression-tree analysis identified 4 groups of oligodendrogliomas with distinctly different outcomes: (1) 32 patients with low-grade tumors and p27 LIs greater than 20%; (2) 14 patients with low-grade tumors and p27 LIs less than 20%; (3) 25 patients with high-grade tumors and Ki-S1 LIs less than 10%; and (4) 20 patients with high-grade tumors and Ki-S1 LIs greater than 10%. Conclusions.—Immunoreactivity for Ki-S1 and p27 was found to be useful for further subdividing oligodendroglioma prognoses among low-grade and high-grade tumors. It seems unlikely that p21 immunohistochemistry will be of value for determining clinical outcomes for patients with oligodendrogliomas.

scholarly journals Homotopic functional connectivity disruptions in glioma patients are associated with tumor malignancy and overall survival

2021 ◽  
Author(s):  
Andy G S Daniel ◽  
Carl D Hacker ◽  
John J Lee ◽  
Donna Dierker ◽  
Joseph B Humphries ◽  
...  
Keyword(s):  
Overall Survival ◽  
Functional Connectivity ◽  
Healthy Subjects ◽  
High Grade Glioma ◽  
Tumor Grade ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Healthy Controls ◽  
Who Grade

Abstract Background Gliomas exhibit widespread bilateral functional connectivity (FC) alterations that may be associated with tumor grade. Limited studies have examined the connection-level mechanisms responsible for these effects. Given the typically strong FC observed between mirroring/homotopic brain regions in healthy subjects, we hypothesized that homotopic connectivity (HC) is altered in low-grade and high-grade glioma patients and the extent of disruption is associated with tumor grade and predictive of overall survival (OS) in a cohort of de novo high-grade glioma (World Health Organization [WHO] grade 4) patients. Methods We used a mirrored FC-derived cortical parcellation to extract blood-oxygen-level-dependent (BOLD) signals and to quantify FC differences between homotopic pairs in normal-appearing brain in a retrospective cohort of glioma patients and healthy controls. Results Fifty-nine glioma patients (WHO grade 2, n = 9; grade 4 = 50; mean age, 57.5 years) and thirty healthy subjects (mean age, 65.9 years) were analyzed. High-grade glioma patients showed lower HC compared to low-grade glioma patients and healthy controls across several cortical locations and resting-state networks. Connectivity disruptions were also strongly correlated with hemodynamic lags between homotopic regions. Finally, in high-grade glioma patients with known survival times (n = 42), HC in somatomotor and dorsal attention networks were significantly correlated with OS. Conclusions These findings demonstrate an association between tumor grade and HC alterations that may underlie global FC changes and provide prognostic information.

scholarly journals The Role of Extent of Resection in IDH1 Wild-Type or Mutant Low-Grade Gliomas

Neurosurgery ◽  
2017 ◽  
Vol 82 (6) ◽  
pp. 808-814 ◽  
Author(s):  
Toral Patel ◽  
Evan D Bander ◽  
Rachael A Venn ◽  
Tiffany Powell ◽  
Gustav Young-Min Cederquist ◽  
...  
Keyword(s):  
Cox Regression ◽  
Extent Of Resection ◽  
World Health ◽  
Low Grade ◽  
Wild Type ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Low Grade Gliomas ◽  
Grade Ii ◽  
The Impact

Abstract BACKGROUND Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. OBJECTIVE To assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS) in mtIDH and wtIDH LGGs. METHODS We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing resection at a single institution. EOR was assessed with quantitative 3-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan–Meier method. RESULTS Fifty-two (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median preoperative tumor volume was 37.4 cm3; median EOR of 57.6% was achieved. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, stratifying by IDH status demonstrates that greater EOR independently prolonged MPFS and OS for wtIDH patients (hazard ratio [HR] = 0.002 [95% confidence interval {CI} 0.000-0.074] and HR = 0.001 [95% CI 0.00-0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17-4.13] and HR = 2.99 [95% CI 0.15-61.66], respectively). CONCLUSION Increasing EOR confers oncologic and survival benefits in IDH1 wtLGGs, but the impact on IDH1 mtLGGs requires further study.

miR-9-1 Is a New Circulating Biomarker for Higher-grade Meningioma Regulated via the EGFR-FOS Network

2020 ◽  
Author(s):  
Daniele Baiz ◽  
Caterina Negroni ◽  
Sara Ferluga ◽  
Emanuela Ercolano ◽  
Claire L Adams ◽  
...  
Keyword(s):  
Tumor Grade ◽  
World Health ◽  
Tumor Growth Rate ◽  
Low Grade ◽  
Serum Samples ◽  
Circulating Biomarker ◽  
Mirna Array ◽  
Malignant Grade ◽  
Health Organization

Abstract Background: Meningiomas are the most common primary CNS tumors. According to the World Health Organization Classification (WHO), they are classified as benign (grade I), atypical (grade II), and anaplastic/malignant (grade III). Chemotherapy has proven ineffective in treating these tumors, which are primarily managed by surgery, radiotherapy, or a combination of them. Morbidity and mortality correlate with meningioma grade. Currently, risk assessment for treatment is based on the radiological assessment of tumor size, tumor growth rate, and/or clinical progression of symptoms. Methods: We performed a cancer miRNA array in an in vitro model of meningioma in order to identify circulating biomarkers in meningioma patients. We validated the miRNA biomarker candidate in cells and tissues and analyzed its regulation. We then investigated expression in tissues and blood. Results: We identified miR-9-1 as significantly overexpressed in atypical and anaplastic cells compared to benign. We further demonstrated that miR-9-1 overexpression is due to increased levels of FOS via upregulation of the EGFR receptor, and showed that miR-9-1 and FOS are upregulated in a cohort of higher-grade meningioma biopsies. Next, we isolated circulating exosomes from meningioma patients’ serum samples, and found higher levels of miR-9-1 in higher-grade compared to low-grade meningiomas patients. Conclusions: Overall, our study shows overexpression and the mechanism of miR-9-1 regulation and suggests miR-9-1 as a novel circulating biomarker candidate to identify tumor grade in meningioma.

scholarly journals Resting-state fMRI detects alterations in whole brain connectivity related to tumor biology in glioma patients

2020 ◽  
Vol 22 (9) ◽  
pp. 1388-1398 ◽  
Author(s):  
Veit M Stoecklein ◽  
Sophia Stoecklein ◽  
Franziska Galiè ◽  
Jianxun Ren ◽  
Michael Schmutzer ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Brain Area ◽  
Tumor Biology ◽  
Resting State Fmri ◽  
World Health ◽  
Low Grade ◽  
Clinical Value ◽  
Isocitrate Dehydrogenase 1 ◽  
Who Grade

Abstract Background Systemic infiltration of the brain by tumor cells is a hallmark of glioma pathogenesis which may cause disturbances in functional connectivity. We hypothesized that aggressive high-grade tumors cause more damage to functional connectivity than low-grade tumors. Methods We designed an imaging tool based on resting-state functional (f)MRI to individually quantify abnormality of functional connectivity and tested it in a prospective cohort of patients with newly diagnosed glioma. Results Thirty-four patients were analyzed (World Health Organization [WHO] grade II, n = 13; grade III, n = 6; grade IV, n = 15; mean age, 48.7 y). Connectivity abnormality could be observed not only in the lesioned brain area but also in the contralateral hemisphere with a close correlation between connectivity abnormality and aggressiveness of the tumor as indicated by WHO grade. Isocitrate dehydrogenase 1 (IDH1) mutation status was also associated with abnormal connectivity, with more alterations in IDH1 wildtype tumors independent of tumor size. Finally, deficits in neuropsychological performance were correlated with connectivity abnormality. Conclusion Here, we suggested an individually applicable resting-state fMRI marker in glioma patients. Analysis of the functional connectome using this marker revealed that abnormalities of functional connectivity could be detected not only adjacent to the visible lesion but also in distant brain tissue, even in the contralesional hemisphere. These changes were associated with tumor biology and cognitive function. The ability of our novel method to capture tumor effects in nonlesional brain suggests a potential clinical value for both individualizing and monitoring glioma therapy.

scholarly journals PATH-65. MOLECULAR SIGNATURE OF FAT1 RELATED MOLECULES IN GLIOMAS IN THE CONTEXT OF THE WHO 2016 CLASSIFICATION

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi158-vi158
Author(s):  
Kunzang Chosdol ◽  
Manvi Arora ◽  
Nargis Malik ◽  
Prerana Jha ◽  
Jyotsna Singh ◽  
...  
Keyword(s):  
Molecular Markers ◽  
In Silico Analysis ◽  
Molecular Signature ◽  
World Health ◽  
Low Grade ◽  
Who Grade ◽  
Inflammatory Microenvironment ◽  
Molecular Features

Abstract Glioblastoma (GBM, WHO grade-IV) being the most malignant and aggressive form of glioma remains a major clinical challenge, with an overall 5-year survival rate of only 9.8%. Till recently, glioma diagnosis and grading were solely dependent on the phenotypic and histological features. However, with the advancement in the understanding of the molecular biology of glioma several molecules have been identified. The importance of these molecular/genotypic features of the tumor became evident by the inclusion of these molecular features by World Health Organization (WHO) in 2016 in glioma sub-grouping. Our lab is focused on studying the role of FAT1 gene (human ortholog of Drosophila tumor suppressor gene, fat) in glioma biology and aggressiveness. We observed FAT1 gene to have an oncogenic role in glioma where it has been found to upregulate migration/invasion, inflammatory microenvironment of the tumors, HIF1α expression/activity in the tumor-cells under severe hypoxia and in regulating EMT/stemness properties of GBM-cells under hypoxia. Here, we have characterized the molecular relationship between FAT1 related molecules and known- molecular markers of glioma with the hope of identifying glioma subgroup with a molecular signature of clinical significance by (i) analyzing the expression correlation of FAT1 and FAT1 regulated pro-inflammatroy molecules like COX2, IL1b and IL6 with the known- molecular markers of glioma like p53, IDH1, MGMT, EGFR, TERT in low-grade (grade-II) and high-grade (grade-III/IV) gliomas (n=50) by real-time PCR, sequencing, immunohistochemistry and in-silico analysis of TCGA-GBM-data (ii) Analyzed the regulatory role of FAT1 on the above known markers by siRNA mediated knockdown of FAT1 in in-vitro cell-culture system and (iii) further analyzed the identified molecular signature for their correlation with the patients prognosis/survival in the follow up patients. We observed a novel molecular signature with significant correlation with patients’ clinical outcome. Therapeutic targetting of FAT1 may benefit patients with high FAT1 expressing tumors.

scholarly journals Analysis of Prognostic Factors of World Health Organization Grade Ⅲ Meningiomas

2020 ◽  
Vol 10 ◽  
Author(s):  
Weidong Tian ◽  
Jingdian Liu ◽  
Kai Zhao ◽  
Junwen Wang ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Postoperative Radiotherapy ◽  
World Health ◽  
Low Grade ◽  
Ki 67 ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

ObjectiveWHO grade III meningiomas are highly aggressive and lethal. However, there is a paucity of clinical information because of a low incidence rate, and little is known for prognostic factors. The aim of this work is to analyze clinical characteristics and prognosis in patients diagnosed as WHO grade III meningiomas.Methods36 patients with WHO grade III meningiomas were enrolled in this study. Data on gender, age, clinical presentation, preoperative Karnofsky Performance Status (KPS), histopathologic features, tumor size, location, radiologic findings, postoperative radiotherapy (RT), surgical treatment, and prognosis were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were conducted by the Cox regression model.ResultsMedian PFS is 20 months and median OS is 36 months in 36 patients with WHO grade III meningiomas. Patients with secondary tumors which transformed from low grade meningomas had lower PFS (p=0.0014) compared with primary group. Multivariate analysis revealed that tumors location (PFS, p=0.016; OS, p=0.013), Ki-67 index (PFS, p=0.004; OS, p<0.001) and postoperative radiotherapy (PFS, p=0.006; OS, p<0.001) were associated with prognosis.ConclusionWHO grade III meningiomas which progressed from low grade meningiomas were more prone to have recurrences or progression. Tumors location and Ki-67 index can be employed to predict patient outcomes. Adjuvant radiotherapy after surgery can significantly improve patient prognosis.

scholarly journals Grade Diagnosis of Human Glioma Based on Fingerprint and Artificial Neural Network

2021 ◽  
Author(s):  
Wenyu Peng ◽  
Shuo Chen ◽  
Dongsheng Kong ◽  
Xiaojie Zhou ◽  
Xiaoyun Lu ◽  
...  
Keyword(s):  
Neural Network ◽  
Artificial Neural Network ◽  
Prediction Accuracy ◽  
Pathological Diagnosis ◽  
World Health ◽  
Low Grade ◽  
Human Glioma ◽  
Who Grade ◽  
Specificity And Sensitivity ◽  
Artificial Neural

Abstract BackgroundThe World Health Organization (WHO) grade diagnosis of cancer is essential for surgical outcomes and patient treatment. Traditional pathological grading diagnosis depends on dyes or other histological approaches, which are time-consuming (usually 1-2 days), resource-wasting, and labor-intensive. Fourier transform infrared (FTIR) spectroscopy is a rapid and nondestructive technique that has been widely used for detecting the molecular component changes, which relies on the resonant frequencies absorbance of the molecular bonds.MethodsTo overcome the disadvantages of traditional pathological diagnosis, this paper proposed a novel diagnostic method based on FTIR and artificial neural network (ANN). Firstly, the spectra of high- and low-grade human glioma that without dye were collected by FTIR spectrometer, then the raw data preprocessed with baseline correction and amide I (1649 cm-1) normalization before input into the input-layer of the ANN, after the nonlinear conversion of the neurons in the hidden-layers, the categories were presented in the output-layer. Corresponding to the decrease of the loss function, the weights of the net updated continuously, and finally, the optimized model has the power of prediction for new samples. ResultsAfter training on 6225 spectra sourced from 77 glioma patients, the ANN model reached the prediction accuracy, specificity and sensitivity evaluation metrics above 99%, which was much superior to the common classification method of principal component analysis-linear discriminate analysis (PCA-LDA) (the prediction accuracy, specificity and sensitivity are only 87%, 89% and 86%, respectively). Moreover, rather than the lipid range of 2800-3000 cm-1, the ANN learned the fingerprint characteristics of the infrared spectrum to classify the major histopathologic classes of human glioma. Especially, the diagnosis process of the novel method only requires several minutes. Compared to the traditional pathological diagnosis, the efficiency raises almost 500 times.ConclusionsThe infrared range of fingerprint is the major indicator for cancer progression, and the ANN-based diagnosis method can be streamlined, and create a complementary pathway that is independent of the traditional pathology laboratory.

scholarly journals FXYD2 mRNA Expression Represents a New Independent Factor That Affects Survival of Glioma Patients and Predicts Chemosensitivity of Patients to Temozolomide

2021 ◽  
Author(s):  
Fang Wang ◽  
Kaijia Zhou ◽  
Tao Jiang ◽  
Hui Liang ◽  
Ming Zhang
Keyword(s):  
Mrna Expression ◽  
Survival Data ◽  
Expression Patterns ◽  
Prognostic Indicator ◽  
World Health ◽  
Independent Factor ◽  
Survival Times ◽  
Who Grade ◽  
Expression Levels ◽  
Mrna Expression Levels

Abstract Glioma is the most common primary intracranial tumor. Owing to the poor prognosis associated with high-grade gliomas, there is an urgent need to identify biomarkers related to prognosis and treatment sensitivity. Clinical features, FXYD2 mRNA expression levels, and survival data were analyzed for 1265 glioma samples from the Chinese Glioma Genome Map Project and two independent databases. The expression patterns for FXYD2 mRNA were compared using the chi-square test, and overall survival (OS) of glioma patients was evaluated according to FXYD2 mRNA expression levels. The factors affecting glioma survival were evaluated by Cox univariate and multivariate regression analysis. We found patients with primary oligodendroglioma, low World Health Organization (WHO) grade, low WHO molecular grade, isocitrate dehydrogenase (IDH) mutation, and combined deletion of 1p19q showed higher FXYD2 mRNA expression and longer survival times. Moreover, temozolomide (TMZ) chemotherapy was found to be an independent factor affecting survival in patients with high FXYD2 mRNA expression, but not in patients with low expression. So FXYD2 mRNA expression represents a new independent factor affecting the survival of glioma patients and may serve as an independent prognostic indicator to predict the sensitivity of gliomas to TMZ.

scholarly journals Prognostic Role of FGFR3 Expression Status and Tumor-Related MicroRNAs Level in Association with PD-L1 Expression in Primary Luminal Non-Muscular Invasive Bladder Carcinoma

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 305
Author(s):  
Ekaterina Blinova ◽  
Anton Buzdin ◽  
Dmitry Enikeev ◽  
Dmitry Roshchin ◽  
Maria Suntsova ◽  
...  
Keyword(s):  
Bladder Carcinoma ◽  
Molecular Subtype ◽  
Tumor Grade ◽  
World Health ◽  
Risk Level ◽  
Low Grade ◽  
European Organization ◽  
Fgfr3 Gene ◽  
Health Organization ◽  
Tissue Specimens

Background: bladder cancer is one of the most common urinary tract malignancies. Establishment of robust predictors of disease progression and outcome is important for personalizing treatment of non-muscular invasive bladder carcinoma (NMIBC). In this study we evaluated association of PD-L1 expression with other prognostic biomarkers, such as expression of miRNA-145 and miRNA-200a, FGFR3 gene expression, and mutation status in tissue specimens of the luminal subtype of newly diagnosed high and low grade NMIBC. Methods: twenty patients with primary luminal NMIBC were enrolled in the study. Tumor grade and risk level were determined in accordance with European Organization for Research and Treatment of Cancer (EORTC) guidelines and World Health Organization (WHO) classification. Neoplasm molecular subtype and PD-L1 expression level were assessed by immunohistochemistry. We used real-time PCR to evaluate the expression of microRNAs and FGFR3. We detected FGFR3 hotspot mutations in codons 248 and 249 by Sanger sequencing. Results: high grade primary luminal NMIBC showed comparatively higher expression of PD-L1 and microRNA-145 than a low grade tumor, whereas the latter had a higher FGFR3 expression and hotspot mutation rate. The tumor grade (HR = 571.72 [11.03–2.96] p = 0.002), PD-L1 expression (HR = 2.33 [0.92–1.92] p = 0.012), and FGFR3 expression (HR = 0.08 [0.17–0.42] p = 0.003) were associated with relapse-free survival. Conclusions: tumor grade in association with PD-L1 and FGFR3 expression can be considered as a complex predictor for primary luminal NMIBC progression.

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