Ki-67 immunostaining in astrocytomas: Association with histopathological grade – A South Indian study

ABSTRACT Background: Astrocytomas are the most common primary tumor of the central nervous system. The distinction between different tumor grades can be tested despite criteria given by the World Health Organization (WHO). Ki-67 is a potent biological marker used in grading of astrocytomas, which estimates growth of the neoplasm quantitatively and will help in predicting prognosis accurately. Objectives: The aim of this was to study the proliferative activity using Ki-67 immunostaining and to assess the relationship of Ki-67 staining with the histopathological grading of astrocytomas. Patients and Methods: Thirty cases of histologically proven astrocytomas were studied. The histopathological grade was assessed using the 2007 WHO criteria. Immunohistochemistry for Ki-67 was done on paraffin-embedded wax sections. P < 0.05 was considered statistically significant. Results: Thirty cases of astrocytomas studied showed a male preponderance (M:F = 1.72:1) with a mean age of 48.1 years. Of these, Grade I, (n = 1, 3.33%), Grade II, (n = 7, 23.3%), Grade III (n = 6, 20%), and Grade IV (n = 16, 53.3%) astrocytomas were analyzed. The mean Ki-67 labeling index (LI) in Grades I, II, III, and IV was 0.02, 0.81, 9.14, and 17.81, respectively. Statistically significant difference was seen in the Ki-67 LI of low-grade (Grade II) and high-grade astrocytomas (Grades III and IV). There was concordance between histopathological grading and Ki-67 LI in 27 (90%) and discordance in 3 (10%) cases. Conclusion: Ki-67 LI varies considerably in different grades of astrocytomas and considerable overlaps can be observed between them. It can be of great help in situations where there is a lack of correlation between clinical parameters and histopathological diagnosis. Determination of Ki-67 LI should constitute a part of routine investigations in patients with astrocytomas.

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5-Aminolevulinic Acid Fluorescence-Guided Resection of Intramedullary Ependymoma: Report of 9 Cases

Operative Neurosurgery ◽

10.1227/neu.0b013e31827bc7a3 ◽

2012 ◽

Vol 72 (2) ◽

pp. ons159-ons168 ◽

Cited By ~ 12

Author(s):

Tomoo Inoue ◽

Toshiki Endo ◽

Kenichi Nagamatsu ◽

Mika Watanabe ◽

Teiji Tominaga

Keyword(s):

Spinal Cord ◽

Aminolevulinic Acid ◽

Tumor Resection ◽

Extent Of Resection ◽

Labeling Index ◽

World Health ◽

Histopathological Diagnosis ◽

Glioma Surgery ◽

Ki 67 ◽

Grade Ii

Abstract BACKGROUND: Resection guided by 5-aminolevulinic acid (5-ALA) fluorescence has proved to be useful in intracranial glioma surgery. However, the effects of 5-ALA on spinal cord tumors remain unknown. OBJECTIVE: To evaluate the usefulness of 5-ALA fluorescence-guided resection of intramedullary ependymoma for achieving maximum tumor resection. METHODS: This study included 10 patients who underwent surgical resection of an intramedullary ependymoma. Nine patients were orally administered 5-ALA (20 mg/kg) 2 hours before the induction of anesthesia. 5-ALA fluorescence was visualized with an operating microscope. Tumors were removed in a standardized manner with electro-physiological monitoring. The extent of resection was evaluated on the basis of intra-operative findings and postoperative magnetic resonance imaging. Histopathological diagnosis was established according to World Health Organization 2007 criteria. Cell proliferation was assessed by Ki-67 labeling index. RESULTS: 5-ALA fluorescence was positive in 7 patients (6 grade II and 1 grade III) and negative in 2 patients (grade II). Intraoperative findings were dichotomized: Tumors covered by the cyst were easily separated from the normal parenchyma, whereas tumors without the cyst appeared to be continuous to the spinal cord. In these cases, 5-ALA fluorescence was especially valuable in delineating the ventral and cranial and caudal margins. Ki-67 labeling index was significantly higher in 5-ALA-positive cases compared with 5-ALA-negative cases. All patients improved neurologically or stabilized after surgery. CONCLUSION: 5-ALA fluorescence was useful for detecting tumor margins during surgery for intramedullary ependymoma. When combined with electrophysiological monitoring, fluorescence-guided resection could help to achieve maximum tumor resection safely.

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Analysis of Minichromosome Maintenance-2 (MCM-2) and Cyclin D1 Expression in Meningioma

Folia Medica Indonesiana ◽

10.20473/fmi.v54i3.10016 ◽

2018 ◽

Vol 54 (3) ◽

pp. 207

Author(s):

Yuliana Kurniawati ◽

Dyah Fauziah

Keyword(s):

Cell Cycle ◽

Cyclin D1 ◽

Malignant Tumors ◽

World Health ◽

Minichromosome Maintenance ◽

Significant Difference ◽

Grade Ii ◽

Health Organization ◽

Anatomical Pathology ◽

Histopathological Grading

World Health Organization histopathological grading of meningioma is associated with recurrence and clinical outcome. Grade II meningioma can be difficult to distinguish with grade I especially in case in which mitosis is not easily identified. MCM-2 and Cyclin D1 play crucial role in cell cycle and have been reported overexpressed in many malignant tumors. The aim of this observational analytic study was to analyze the differences and correlation between MCM-2 and Cyclin D1 in various meningioma grading. Immunohistochemystry with MCM-2 and Cyclin D1 was performed on 25 paraffin blocks of grade I, II and III meningiomas at the Laboratory of Anatomical Pathology, Dr. Soetomo Hospital. The immunoexpression are evaluated using Labelling Index, then analyzed statistically. The results showed significant difference in expression of MCM-2 within various meningioma grading (p=0.000) and significant difference in expression of Cyclin D1 within grade I and II also within grade I and III (p<0.050), but not in grade II and III (p>0.050). There was also positive correlation between MCM-2 and Cyclin D1 expression in various meningioma grading (rs=0.683, p=0.000). MCM-2 may play role in distinguishing various meningioma grading. Cyclin D1 can distinguish grade I and II also grade I and III, but not grade II and III. Overexpression MCM-2 was along with Cyclin D1 in various meningioma gradings.

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Investigation of the Relationship Between the Degree of Peritumoral Brain Edema and Pathological Features of Glioma Before Surgery

Iranian Journal of Radiology ◽

10.5812/iranjradiol.109181 ◽

2021 ◽

Vol 18 (3) ◽

Author(s):

Zhenhua Wang ◽

Xinlan Xiao

Keyword(s):

Brain Edema ◽

Malignant Tumors ◽

Multivariate Logistic Regression Analysis ◽

Expression Level ◽

World Health ◽

Low Grade ◽

Ki 67 ◽

Mutation Status ◽

Significant Difference ◽

Peritumoral Brain Edema

Background: Gliomas are the most common malignant tumors of the central nervous system (CNS). Preoperative prediction of the malignancy grade of gliomas are of particular importance. These tumors are often accompanied by peritumoral brain edema (PTBE). Previous studies have suggested that the degree of PTBE is an independent indicator of the prognosis of gliomas. Objectives: This study aimed to investigate the relationships between the degree of PTBE and the grade of glioma, isocitrate dehydrogenase 1 (IDH1) mutation status, and Ki-67 expression level in gliomas. Patients and Methods: In this retrospective cross-sectional study, a total of 82 patients were enrolled, according to the 2016 World Health Organization (WHO) classification of CNS tumors. Overall, 29 tumors were pathologically confirmed as low-grade gliomas (LGGs , grade I-II), whereas the remaining 53 tumors were classified as high-grade gliomas (HGGs, grade III-IV). The IDH1 mutations, Ki-67 expression, and magnetic resonance imaging (MRI) findings were retrospectively analyzed. The tumor and tumor + PTBE volumes were also measured, and the tumor edema index (EI) was calculated for each patient. Edema was then graded and correlated with the pathological parameters. Results: The degree of EI was higher in the HGG group compared to the LGG group, and the difference was statistically significant (z = -7.018, P < 0.05). Besides, the degree of EI was higher in the IDH1 wild-type compared with mutant groups (z = -4.116, P < 0.05). The degree of EI significantly associated with Ki-67 expression and patient’s age (P < 0.05), whereas there was no significant association between the degree of EI and gender (z = -0.497, P = 0.619). The Spearman’s correlation test revealed that the EI degree was positively correlated with the Ki-67 expression level and age, with correlation coefficients of 0.740 and 0.466, respectively. Moreover, the multivariate logistic regression analysis indicated that EI and IDH1 had significant effects on differentiating LGGs from HGGs (P < 0.05 for both). The receiver operating characteristic (ROC) curve analysis showed that EI was an optimal index for differentiating LGGs from HGGs, with an area under curve (AUC) of 0.822 (cutoff value: 1.722, sensitivity: 95.8%, specificity: 70.0%, 95% CI: 0.718 - 0.899). Conclusion: The degree of PTBE was found to be a valuable index for the differential diagnosis of LGGs from HGGs. It has a significant difference between IDH1 wild and mutation status, furthermore, it was positively correlated with the age and Ki-67 level.

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

Neurosurgery ◽

10.1093/neuros/nyx265 ◽

2017 ◽

Vol 82 (6) ◽

pp. 808-814 ◽

Cited By ~ 20

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.

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Characteristics and Histopathological Grading of Malignant Spiculated Mass in regards to Histopathological Grading of Breast Cancer Based on The Nottingham Grading System

Biomolecular and Health Science Journal ◽

10.20473/bhsj.v3i1.19134 ◽

2020 ◽

Vol 3 (1) ◽

pp. 33

Author(s):

Andi Syarti ◽

Ulinta Pasaribu ◽

Dyah Fauziah ◽

Lies Mardiyana ◽

Tri Wulanhandarini

Keyword(s):

Breast Cancer ◽

Mitotic Index ◽

Proliferation Index ◽

Grading System ◽

Nuclear Pleomorphism ◽

Histopathological Grade ◽

Grade Ii ◽

Tubular Formation ◽

Histopathological Grading ◽

Grade Iii

Introduction: Spiculation in mammography is a typical finding for invading breast cancer and is an important criterion in diagnosis and in predicting prognostic and plays an important role in management. The purpose of this research is to determine the characteristics of malignant spiculating mass in mammography in regards to histopathological grading using The Nottingham Grading System.Methods: Patients whom had spiculation in mammography was reviewed using medical record data by two breast imaging consultants and then combined with The Nottingham Grading System criteria obtained from histopathological examination results of core biopsy and surgery specimen. There was 29 cases that met the inclusion criteria.Results: Of the 29 patients that met the inclusion, the spiculated masses grade I, II has mitotic index of 0-12, grade III has mitotic index of 13-25. Histopathologic grade II, III has the most tubular formation of <10%, grade I has 10-75%. Grade I, II has moderate nuclear pleomorphism, grade III has severe nuclear pleomorphism. Most were grade III (44.8%), followed by grade II (37.9%), and minimally grade I (17.2%). Most patients are in stage 3 breast cancer.Conclusion: Malignant spiculated mass with grade I, II has low proliferation index (mitotic index 0-12), histopathological grade II, III had worse cellular differentiation (tubular formation <10%), histopathological grade II, III has moderate to severe nuclear pleomorphism.

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Accuracy of Intraoperative Examination in Central Nervous System Lesions: A Study of 133 Cases

Acta Cytologica ◽

10.1159/000495175 ◽

2019 ◽

Vol 63 (3) ◽

pp. 224-232

Author(s):

Ludmila Barbosa de Souza Balsimelli ◽

Jamille Costa de Oliveira ◽

Flora Ávila Adorno ◽

Clarissa Almeida Brites ◽

Giuliano Stefanello Bublitz ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Frozen Section ◽

Final Diagnosis ◽

World Health ◽

Histopathological Diagnosis ◽

Low Grade ◽

Predictive Values ◽

Health Organization ◽

Cns Lesions

Objective: Intraoperative examination is a highly valuable tool for the evaluation of central nervous system (CNS) lesions, helping the neurosurgeon to determine the best surgical management. This study aimed to evaluate the accuracy and to analyze the diagnostic disagreements and pitfalls of the intraoperative examinations through correlation with the final histopathological diagnosis in CNS lesions. Study Design: Retrospective analysis of intraoperative examination of CNS lesions and their final diagnosis obtained during 16 consecutive years. All diagnoses were reviewed and classified according to World Health Organization (WHO) grading for CNS tumors. Squash was performed in 119 cases, while frozen section and both methods were done in 7 cases each. Results: Among the 133 intraoperative examinations considered, 114 (85.7%) presented concordance and 19 (14.3%) diagnostic disagreement when compared with subsequent histopathological examinations. The sensitivity and specificity for the detection of neoplasia in intraoperative examination was 98 and 94%, respectively. The positive and negative predictive values were 99 and 88%, respectively. The accuracy for neoplastic and nonneoplastic disease was 85.7%. Disagreements were more frequent among low-grade (WHO grades I and II) neoplasms and nonmalignant cases. Conclusions: Our results showed good accuracy of the intraoperative assessments for diagnosis of CNS lesions, particularly in high-grade (grades III and IV) lesions and metastatic neoplasms.

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Analysis of Prognostic Factors of World Health Organization Grade Ⅲ Meningiomas

Frontiers in Oncology ◽

10.3389/fonc.2020.593073 ◽

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.

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The Expressions of Wnt/β-catenin Pathway-Related Components in Brainstem Gliomas

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s031716710001430x ◽

2013 ◽

Vol 40 (3) ◽

pp. 355-360 ◽

Cited By ~ 14

Author(s):

Wenhao Wu ◽

Yongji Tian ◽

Hong Wan ◽

Yongmei Song ◽

Junhua Li ◽

...

Keyword(s):

Signaling Pathway ◽

Clinicopathological Characteristics ◽

Current Treatment ◽

Brainstem Glioma ◽

Low Grade ◽

Normal Brain ◽

Ki 67 ◽

Significant Difference ◽

The Relationship ◽

Brain Tissues

Background:The overall prognosis of brainstem gliomas is very poor, and the current treatment cannot significantly prolong the overall survival of these patients; therefore, studying the molecular biological mechanisms of the occurrence and development of brainstem gliomas has important significance for their treatment. The Wnt/β-catenin signaling pathway is closely associated with the occurrence and development of tumors, but its relationship with brainstem gliomas remains unclear.Methods:This study used Western blot and immunohistochemistry methods to detect the expressions of Wnt/β-catenin signaling pathway-related components such as Wnt-1, Wnt-2, β-catenin and C-myc in six cases of normal brain tissues and 24 cases of brainstem gliomas and analyzed the relationship between their expressions and clinicopathological characteristics.Results:Wnt-1 had no obvious expression in normal brain tissues and did not show any significant difference between high- and low-grade brainstem gliomas; the expressions of Wnt-2, β-catenin and C-myc in high-grade brainstem gliomas were significantly higher than that in low-grade brainstem gliomas and normal brain tissues and were positively correlated with the expression of Ki-67. Moreover, the expressions of Wnt-2 and C-myc were significantly associated with the prognosis of brainstem glioma patients; additionally, there was a trend toward increased β-catenin expression with shorter survival, but there was no statistical difference.Conclusions:Wnt/β-catenin signaling pathway might be abnormally activated and plays an important role in the occurrence and development of brainstem gliomas. Wnt-2, β-catenin and C-myc may be potential targets for brainstem glioma treatment.

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Clinicohistopathological study of astrocytomas along with Ki-67 proliferative index

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20180317 ◽

2018 ◽

Vol 6 (2) ◽

pp. 665 ◽

Cited By ~ 1

Author(s):

Basumitra Das ◽

Kurimella Vamsya Raj ◽

Bhagyalakshmi Atla

Keyword(s):

Histological Grade ◽

Research Work ◽

Low Grade ◽

Proliferative Index ◽

Ki 67 ◽

Biologic Marker ◽

Grade Ii ◽

The Mean ◽

The Difference ◽

Grade Iii

Background: Astrocytomas form the largest group of gliomas (>75%) and diffusely infiltrating accounting for more than 60% of all the primary brain tumors. The ki67 proliferative index is a potent biologic marker that estimates the growth of neoplasms quantitatively and thus will aid in identifying the prognosis for patients with neoplasms. The aim of the research work was to study various histopathological and clinical features of Astrocytomas in detail, to evaluate Ki-67 proliferative index in patients of Astrocytomas and to compare the results of Immunohistochemistry with histological grade of Astrocytomas.Methods: A total number of 40 cases of Astrocytomas were included in the study. Ki-67 immunostaining was done on all cases and compared with WHO histological grading of astrocytomas.Results: The mean Ki‑67 LI in Grade I astrocytomas was 4.66, range 4-5 , in Grade II astrocytomas mean was 8.07, range 5-12 ,in Grade III astrocytomas mean was 13.5 , range 8-20, in Grade IV astrocytomas mean was 22.93, range 15-50. There was a highly significant correlation between the histopathological grade of astrocytomas and Ki-67 LI (p<0.05).Conclusions: The monoclonal antibody Ki-67 has proven its prognostic and diagnostic power in astrocytic tumors. Ki-67 LI is the simplest and the most reliable method for evaluating cell proliferation. Ki-67 LI increased with histological grade and the difference between low grade (I and II astrocytomas) and high grade (grade III and IV) is significant. In the present study Ki-67 LI is not dependent on factors like age and sex and is solely dependent on histological grade.

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RADIOMICS BASED SINGLE AND MULTI-CLASS GLIOMA CLASSIFICATION USING SUPPORT VECTOR MACHINE VARIANTS

Biomedical Sciences Instrumentation ◽

10.34107/yhpn9422.04265 ◽

2021 ◽

Vol 57 (2) ◽

pp. 265-273

Author(s):

P.D. Seema ◽

◽

T. Bobby Christy ◽

K.R. Anandh ◽

◽

...

Keyword(s):

Support Vector Machine ◽

Classification Accuracy ◽

Clinical Decision Making ◽

World Health ◽

Support Vector ◽

Low Grade ◽

Whole Brain ◽

Grade Ii ◽

Linear Svm ◽

Grade Iii

The common type of primary brain tumor is glioma. The mortality rate of glioma patients is high due to delayed diagnosis, incorrect grading and treatment planning. Traditionally, gliomas were classified into Low Grade (grade-I and grade-II) and High Grade (grade-III and grade-IV). However, World Health Organization has insisted to classify the grades into grade-I(G-I), grade II(G-II), grade III(G-III) and grade IV(G-IV) individually to aid the physicians in clinical decision-making. Although there are limited number of studies reported to differentiate individual grades, the classification accuracy was low. Consequently, in this work single-class (G-II vs. G-III, G-II vs. G-IV and G-III vs. G-IV) and multi-class (G-II vs. G-III+IV, G-III vs. G-II+IV and G-IV vs. G-II+III) analysis was performed using specific region of tumor and whole brain as Regions of Interest(ROI) by extracting radiomic features. The images for this study (N=75) were obtained from The Cancer Imaging Archive. Further, the statistically significant features were used in the classification of individual grades by implementing variants of Support Vector Machine (SVM) algorithm: SVM, Linear-SVM and Least-Squared SVM. Among these, Linear-SVM resulted in the highest classification accuracy (>80%) with average sensitivity, specificity and AUC values of >70%. The comparative analysis of whole brain versus tumor ROI showed that the latter yielded better classification accuracy.

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