Correlation of PD-L1 with VEGF and KI-67 index in patients with primary glioma.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 94-94
Author(s):  
Song Xue ◽  
Man Hu ◽  
Jinming Yu ◽  
Bingjie Fan ◽  
Ji Ma
Keyword(s):  
Immune Escape ◽  
Treatment Strategies ◽  
High Grade Glioma ◽  
Continuous Variable ◽  
Low Grade ◽  
High Grade ◽  
Grade Group ◽  
Ki 67 ◽  
Primary Glioma ◽  
The Mean

94 Background: The treatment strategies for glioma, especially glioblastoma multiforme, are not effective. The programmed death ligand 1 (PD-L1) immune escape and increased angiogenesis may be two of the underlying sources of treatment resistance. However, the relationship between these pathways in human glioma is still unknown. Methods: Data for 64 patients with primary glioma recorded from June 2007 to December 2013 in Shan Dong Cancer Hospital were immunohistochemically evaluated for the expressions of PD-L1, VEGF, MMP-9 and KI-67 index. Image ProPlus software was used to quantify the mean optical density (MOD) of the immunohistochemical image. Results: PD-L1 expression was observed in 65.22% of low-grade glioma and 90.24% of high-grade glioma, respectively. The whole expression rate of PD-L1 in glioma was 81.25%. The expression of PD-L1 is significantly related to pathological grade ( p <0.001), VEGF ( p= 0.017) and KI-67 index ( p= 0.009). The mean of PD-L1 MOD in High-grade group was 0.1144±0.02754, higher than that in low-grade group, 0.005129±0.001441 ( p= 0.004). In addition, Expression of VEGF, MMP-9 and KI-67 was significantly different between low-grade and high-grade gliomas ( p= 0.008, 0.04, 0.004 for VEGF, MMP-9 and KI-67, respectively). When analyzed as a continuous variable, the expressions of PD-L1 was positively correlated with VEGF (r = 0.392, p= 0.001) and KI-67 (r = 0.388, p= 0.001). Conclusions: These data suggest, for the first time, that PD-L1 play an important role in glioma angiogenesis and proliferation potential, providing the possibility for considering additional combinations of targeted VEGF therapies and anti-PD-L1 immunotherapy for the treatment of human brain glioma.

scholarly journals Ki-67 expression in anal intraepithelial neoplasia in AIDS

2001 ◽  
Vol 119 (3) ◽  
pp. 119-121 ◽  
Author(s):  
Edenilson Eduardo Calore ◽  
Carmen Ruth Manzione ◽  
Sidney Roberto Nadal ◽  
Maria José Cavalieri ◽  
Nilda Maria Perez Calore ◽  
...  
Keyword(s):  
Lower Layer ◽  
Intraepithelial Neoplasia ◽  
Cell Counting ◽  
Biological Behavior ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Staining Techniques ◽  
The Mean ◽  
Group 2

CONTEXT: AIDS is one of the most important risk factors for progression and recurrence of anogenital condyloma. In a previous work, we observed that patients with warts and high-grade AIN (HAIN) had recurrences more frequently than did patients with warts without AIN. The mechanisms of this increased incidence of high-grade lesions in AIDS are not known. OBJECTIVE: We studied the expression of the proliferative marker Ki-67 by immunohistochemical methods, in specimens of anal condyloma from HIV+ patients to clarify whether its expression can be associated to the grade of AIN. DESIGN: A retrospective study of hiltological specimens. SETTING: University referral unit. SAMPLE: 34 patients were divided into two groups: (1) condylomas with low grade AIN (LAIN), with 25 patients; and (2) condylomas with HAIN, with 9 patients. In this latter group we examined two areas: 2A (HAIN area) and 2B (LAIN area). MAIN MEASUREMENTS: The immunohistochemical reaction for Ki-67 was done on histological sections. Slices were lightly stained with hematoxylin, to help us in Ki-67 positive cell counting. The percentage of Ki-67 marked nuclei was calculated. We applied one-way variance analysis for statistics. RESULTS: The mean number of Ki-67 positive cells in group 1 was 19.68 ± 10.99; in group 2 (area A) it was 46.73 ± 10.409; and in area B it was 36.43 ± 14.731. There were statistical differences between groups 1 and 2A and between groups 1 and 2B. Ki-67 positive cells predominated in the lower layer in LAIN. Positive Ki-67 cells were found in all layers in group 2A, and in group 2B they predominated in the two lower or in all layers of the epithelium. CONCLUSIONS: Our results suggest that LAIN areas (using routine staining techniques) in HAIN can have a biological behavior more similar to HAIN.

Diffusion Weighted Imaging of Brain Gliomas in the Differential Diagnosis Value

2020 ◽  
Author(s):  
Jian JIANG ◽  
Liangcai BAI ◽  
Xueling ZHANG ◽  
Jianli LIU ◽  
Junlin ZHOU
Keyword(s):  
Brain Metastases ◽  
Diffusion Weighted Imaging ◽  
High Grade Glioma ◽  
Low Grade Glioma ◽  
Control Group ◽  
Low Grade ◽  
High Grade ◽  
Imaging Data ◽  
Grade Group ◽  
Diffusion Weighted

Background: To evaluate the diagnostic value of diffusion weighted imaging (DWI) and apparent diffusion coefficient measurement (ADC) in glioma. cient measurement (ADC) in glioma. Methods: Thirty two low-grade glioma patients and 31 high-grade glioma patients who were confirmed by pathology in Lanzhou University Second Hospital, Lanzhou, China from February 2016 to January 2019 were selected. The other 30 patients with brain metastases were selected as a control group. DWI imaging data of the three groups were collected, and ADC, relative ADC (rADC) values in tumor parenchyma, peritumor edema area, and contralateral normal white matter area were measured, and the levels of n-acetyl aspartic acid (NAA), choline (Cho), creatine (Cr) of tumor metabolites were analyzed. Results: rADC values in the peri-tumor edema areas of the high-grade glioma group were significantly lower than those in the low-grade group and the metastatic group （P=0.011）, and the low-grade group was significantly lower than that in the metastatic group (P < 0.05). NAA/Cho and NAA/Cr in parenchymal and peritumor edema areas of patients in the advanced group were significantly lower than those in the metastatic group (P < 0.05), and Cho /Cr was significantly higher than those in the metastatic group (P < 0.05). Conclusion: the rADC value, NAA/Cho, NAA/Cr and Cho/Cr in parenchymal and peritumor edema areas of the tumor can help to distinguish high-grade glioma, low-grade glioma and brain metastases.

Survivin as a Useful Adjunct Marker for the Grading of Papillary Urothelial Carcinoma

2008 ◽  
Vol 132 (2) ◽  
pp. 224-231
Author(s):  
Ying-bei Chen ◽  
Jiangling J. Tu ◽  
Jean Kao ◽  
Xi K. Zhou ◽  
Yao-Tseng Chen
Keyword(s):  
Urothelial Carcinoma ◽  
Messenger Rna ◽  
Interobserver Variability ◽  
World Health ◽  
Low Grade ◽  
Nuclear Staining ◽  
High Grade ◽  
Grade Group ◽  
Ki 67 ◽  
Papillary Urothelial Carcinoma

Abstract Context.—Distinguishing low-grade and high-grade noninvasive papillary urothelial carcinoma based on morphologic criteria can be challenging and adjunct markers are highly desirable. Survivin, presumably an antiapoptotic protein, was previously proposed as a prognostic marker for urothelial carcinoma. Objective.—To assess interobserver variability by 2004 World Health Organization classification and the value of survivin and Ki-67 as potential markers for grading noninvasive papillary urothelial carcinoma. Design.—Fifty-one bladder biopsies were graded blindly by 5 experienced general surgical pathologists. The protein and messenger RNA expression of survivin and Ki-67 was evaluated by immunohistochemistry and quantitative reverse transcription–polymerase chain reaction using paraffin-embedded tissue. The immunohistochemistry result was quantitatively analyzed using a computer-based color deconvolution module. Results.—The diagnostic agreement among 5 pathologists was fair to poor, with 32% of the cases graded differently by at least 2 raters. All cases were divided into 3 groups: consensus low-grade, consensus high-grade, and indeterminate. The percentage of urothelial cells with positive survivin nuclear staining (survivin score) was significantly higher in the high-grade than in the low-grade group (P &lt; .001). Survivin score outperformed Ki-67 in separating the high-grade group from the low-grade group and showed a significantly higher predictive accuracy for high-grade recurrence than the histologic grade. The disagreement of grading for the indeterminate group could be resolved by their survivin scores in most cases. Survivin messenger RNA level correlated well with survivin score by immunohistochemistry but was not a more discriminating marker. Conclusions—Significant interobserver variability exists in grading low-grade versus high-grade papillary urothelial carcinoma. Survivin immunohistochemical staining can be a useful adjunct tool for the grading of challenging cases.

scholarly journals Clinicopathological evaluation of immunohistochemical Ki-67 and endothelial nitric oxide synthase expression in intracranial ependymoma

2008 ◽  
Vol 31 (4) ◽  
pp. 206 ◽  
Author(s):  
Xuetao Yan ◽  
Xiaoli Cheng ◽  
Juyin Liu ◽  
Dongqin Luo ◽  
Xianghu He ◽  
...  
Keyword(s):  
Tumour Resection ◽  
Low Grade ◽  
High Grade ◽  
Enos Expression ◽  
Grade Group ◽  
Ki 67 ◽  
Tissue Samples ◽  
Cell Counts ◽  
Positive Expression ◽  
Intracranial Ependymoma

Purpose: To analyze the association between Ki-67 and eNOS expression with the pathological grades of patients with intracranial ependymomas, and to determine its value in distinguishing the progression of the disease. Methods: A clinicopathological study was undertaken in 82 patients with intracranial ependymomas. Tissue samples, obtained by tumour resection, were divided into three groups: low-grade, mid-grade and high-grade ependymomas. Tissue samples obtained from 15 patients with brain contusion were used as control. Immuno-histochemical staining was performed to analyze the association between Ki-67 and eNOS expression with various tumour grades. The cell proliferating marker Ki-67 was assessed by positive cell count. The levels of eNOS positive expression were evaluated as slight, moderate and intense. Results: 48 of 82 cases (58.54%) expressed Ki-67 protein. Expression of Ki-67 and eNOS was negative in all control samples. Positive cell rates were 2.65±0.83 % in the low-grade, 9.63±0.08 % in the mid-grade, and 28.41±0.71 % in the high-grade ependymoma groups. In low-grade ependymomas there were 8 and 12 cases that expressed eNOS slightly or moderately. In the mid-grade ependymoma group eNOS was expressed moderately in 10 cases and intensely in 15. In the high-grade group 20 cases showed intense positive expression of eNOS. The Ki-67 positive cell counts for slight, moderate and intense eNOS expression were 2.20, 6.07 and 22.25, respectively. Conclusion: Ki-67 and eNOS expression in intracranial ependymoma tissue was associated with the histopathological grade and malignant degree.

Apparent diffusion coefficient values and non-homogeneity of diffusion in brain tumors in diffusion-weighted MRI

2019 ◽  
Vol 61 (2) ◽  
pp. 244-252
Author(s):  
Sedigheh Basirjafari ◽  
Masoud Poureisa ◽  
Babak Shahhoseini ◽  
Mohammad Zarei ◽  
Saeideh Aghayari Sheikh Neshin ◽  
...  
Keyword(s):  
Diffusion Coefficient ◽  
Standard Deviation ◽  
Brain Tumors ◽  
Region Of Interest ◽  
Low Grade ◽  
High Grade ◽  
Ki 67 ◽  
Apparent Diffusion ◽  
Adc Values ◽  
The Mean

Background The values that have been received from apparent diffusion coefficient (ADC) maps of diffusion-weighted magnetic resonance imaging (DW-MRI) might play a vital role in evaluating tumors and their grading scale. Purpose To investigate the predictive role of this heterogeneity in brain tumor pathologies and its correlation with Ki-67. Material and Methods A total of 124 patients with brain tumors underwent brain MRI with gadolinium injection. ADC and standard deviation of each lesion have been obtained from manual localization of the region of interest on the ADC map. A receiver operating characteristic analysis was conducted to determine the minimum cut-off values of the mean ADC and mean standard deviation of ADC maps having the highest sensitivity and specificity to differentiate high-grade and low-grade tumors. Results Mean ADC values in the region of interest were significantly lower for malignant tumors (grade IV and metastasis) than grade I brain tumors, while a higher mean standard deviation was observed. In a more detailed comparison of tumor groups, the mean standard deviation of the ADC for glioblastoma multiform was significantly higher than meningioma grade I ( P < 0.001) and metastasis was significantly higher than grade III and IV astrocytic tumors ( P = 0.004). The analysis of Ki-67 proliferation index and mean ADC values in gliomas showed a significant inverse correlation between the parameters (r = –0.0429, P < 0.001) and direct correlation between Ki-67 and mean standard deviation of the ADC (r = 0.551, P < 0.001). As an index for the ADC to differentiate high-grade and low-grade tumors, the cut-off values of 1.40*10−3 mm2/s for mean ADC and 45*10−3 mm2/s for mean standard deviation have the highest combination of sensitivity, specificity, and area under the curve. Conclusion The mean value and standard deviation of the ADC could be considered for differentiating between low-grade and high-grade brain tumors, as two available non-invasive methods.

Correlation among magnetic resonance imaging findings, prognostic factors for survival, and histological diagnosis of intrinsic brainstem lesions in children

2011 ◽  
Vol 8 (6) ◽  
pp. 539-543 ◽  
Author(s):  
Marcos Dellaretti ◽  
Gustavo Touzet ◽  
Nicolas Reyns ◽  
François Dubois ◽  
Sebastião Gusmão ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Mr Imaging ◽  
High Grade Glioma ◽  
Brainstem Glioma ◽  
Low Grade ◽  
Diffuse Glioma ◽  
High Grade ◽  
Brainstem Lesion ◽  
Brainstem Lesions ◽  
The Mean

Object The aim of this study was to compare MR imaging characteristics with histopathological findings of intrinsic brainstem lesions and also to show the prognostic factors in patients with diffuse brainstem glioma. Methods Between February 1988 and August 2007, 44 brainstem biopsies were performed at the Roger Salengro Hospital in Lille, France, in children with intrinsic brainstem lesions not amenable to excision. Twenty-six were female and 18 male, and the mean age was 6 years. Results Histological evaluation revealed diffuse brainstem glioma in all patients with diffuse nonenhancing brainstem lesions. Diffuse brainstem glioma was found in 18 patients (90%) with diffuse enhancing brainstem lesions. Pathological entities different from diffuse glioma were verified in 2 patients (10%)—1 with ependymoma and 1 with ganglioglioma. In 4 of 5 patients with a focal nonenhancing brainstem lesion, the histopathological diagnosis was diffuse low-grade glioma. In 6 of 10 patients with focal enhancing brainstem lesion, the diagnosis was diffuse brainstem glioma, and pathological entities different from diffuse brainstem glioma were verified in 2 (20%), both with pilocytic astrocytoma. The mean 1-year actuarial survival rates for patients classified with low-grade and high-grade glioma were 80.4% ± 0.08% and 48.6% ± 0.14%, respectively. Conclusions The impact of stereotactic biopsy on intrinsic brainstem lesions was greater in patients with MR imaging–documented enhancing lesions in whom the diagnosis of diffuse glioma was less frequent. Patients with low-grade glioma seem to have longer survival than those with high-grade glioma.

scholarly journals Against the Resilience of High-Grade Gliomas: The Immunotherapeutic Approach (Part I)

2021 ◽  
Vol 11 (3) ◽  
pp. 386
Author(s):  
Alice Giotta Lucifero ◽  
Sabino Luzzi
Keyword(s):  
Monoclonal Antibodies ◽  
Natural Killer ◽  
Immune Escape ◽  
Meta Analysis ◽  
Treatment Options ◽  
High Grade Glioma ◽  
High Grade ◽  
Future Challenges ◽  
Genetic Landscape ◽  
High Grade Gliomas

The resilience of high-grade gliomas (HGGs) against conventional chemotherapies is due to their heterogeneous genetic landscape, adaptive phenotypic changes, and immune escape mechanisms. Innovative immunotherapies have been developed to counteract the immunosuppressive capability of gliomas. Nevertheless, further research is needed to assess the efficacy of the immuno-based approach. The aim of this study is to review the newest immunotherapeutic approaches for glioma, focusing on the drug types, mechanisms of action, clinical pieces of evidence, and future challenges. A PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis)-based literature search was performed on PubMed/Medline and ClinicalTrials.gov databases using the keywords “active/adoptive immunotherapy,” “monoclonal antibodies,” “vaccine,” and “engineered T cell.”, combined with “malignant brain tumor”, “high-grade glioma.” Only articles written in English published in the last 10 years were selected, filtered based on best relevance. Active immunotherapies include systemic temozolomide, monoclonal antibodies, and vaccines. In several preclinical and clinical trials, adoptive immunotherapies, including T, natural killer, and natural killer T engineered cells, have been shown to be potential treatment options for relapsing gliomas. Systemic temozolomide is considered the backbone for newly diagnosed HGGs. Bevacizumab and rindopepimut are promising second-line treatments. Adoptive immunotherapies have been proven for relapsing tumors, but further evidence is needed.

scholarly journals Pancreatic Cancers with High Grade Tumor Budding Exhibit Hallmarks of Diminished Anti-Tumor Immunity

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1090
Author(s):  
Hassan Sadozai ◽  
Animesh Acharjee ◽  
Thomas Gruber ◽  
Beat Gloor ◽  
Eva Karamitopoulou
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Disease Progression ◽  
Immune Escape ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Budding ◽  
Ductal Adenocarcinoma ◽  
Low Grade ◽  
High Grade ◽  
Mesenchymal Transition

Tumor budding is associated with epithelial-mesenchymal transition and diminished survival in a number of cancer types including pancreatic ductal adenocarcinoma (PDAC). In this study, we dissect the immune landscapes of patients with high grade versus low grade tumor budding to determine the features associated with immune escape and disease progression in pancreatic cancer. We performed immunohistochemistry-based quantification of tumor-infiltrating leukocytes and tumor bud assessment in a cohort of n = 111 PDAC patients in a tissue microarray (TMA) format. Patients were divided based on the ITBCC categories of tumor budding as Low Grade (LG: categories 1 and 2) and High Grade (HG: category 3). Tumor budding numbers and tumor budding grade demonstrated a significant association with diminished overall survival (OS). HG cases exhibit notably reduced densities of stromal (S) and intratumoral (IT) T cells. HG cases also display lower M1 macrophages (S) and increased M2 macrophages (IT). These findings were validated using gene expression data from TCGA. A published tumor budding gene signature demonstrated a significant association with diminished survival in PDAC patients in TCGA. Immune-related gene expression revealed an immunosuppressive TME in PDAC cases with high expression of the budding signature. Our findings highlight a number of immune features that permit an improved understanding of disease progression and EMT in pancreatic cancer.

scholarly journals HGG-12. A CASE OF PEDIATRIC SPINAL HIGH-GRADE GLIOMA WITH NTRK1 GENE FUSION

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii346-iii346
Author(s):  
Tamaki Morisako ◽  
Daisuke Umebayashi ◽  
Kazuaki Kamata ◽  
Hiroyuki Yamamoto ◽  
Takumi Yamanaka ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mr Imaging ◽  
Tumor Progression ◽  
Gene Fusion ◽  
High Grade Glioma ◽  
Gene Panel ◽  
Partial Resection ◽  
Low Grade ◽  
High Grade ◽  
Surgical Specimen

Abstract INTRODUCTION Tumors arising from the spinal cord are uncommon, especially high-grade tumors in pediatric patients. We report a case of high-grade glioma in the spinal cord harboring NTRK1 gene fusion, who received effective entrectinib therapy. CASE REPORT: A 5-year-old boy presented right hemiparesis and MR imaging revealed an intramedullary enhancing mass at the vertebral body level between C3 and Th1. He underwent microsurgical partial resection and the histological diagnosis was low-grade astrocytoma. After the first-line chemotherapy with vincristine and carboplatin, his right hemiparesis deteriorated and recurrent MR imaging showed growth of the tumor. He underwent microsurgical partial resection again and the histological examination was high-grade glioma with endothelial proliferation and necrosis. The chemoradiotherapy with temozolomide and focal irradiation of 50.4 Gy were given, and his neurological symptom slightly improved. One month later, he presented respiratory disturbance and required assisted ventilation with tracheostomy. MR imaging showed tumor progression invading upward to medulla oblongata. NTRK1 gene fusion was detected in the previous surgical specimen by a gene panel testing, and he received entrectinib, a potent inhibitor of tropomyosin receptor kinase (TRK). Since then, no tumor progression has been demonstrated for several months by MRI and he has been stable neurologically. CONCLUSION High-grade spinal cord tumors are rare and effective treatment strategies have not been addressed. Although the frequency of the gene fusion is very low in pediatric gliomas, identification of the driver gene aberration like in this case by a gene panel can provide potential targeted therapies for selected patients.

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