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

Author(s):  
Wenhao Wu ◽  
Yongji Tian ◽  
Hong Wan ◽  
Yongmei Song ◽  
Junhua Li ◽  
...  

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.

2020 ◽  
Vol 7 (6) ◽  
pp. 656-667
Author(s):  
Maria R Ponisio ◽  
Jonathan E McConathy ◽  
Sonika M Dahiya ◽  
Michelle M Miller-Thomas ◽  
Keith M Rich ◽  
...  

Abstract Background MRI alone has limited accuracy for delineating tumor margins and poorly predicts the aggressiveness of gliomas, especially when tumors do not enhance. This study evaluated simultaneous 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (FDOPA)-PET/MRI to define tumor volumes compared to MRI alone more accurately, assessed its role in patient management, and correlated PET findings with histopathology. Methods Ten patients with known or suspected gliomas underwent standard of care surgical resection and/or stereotactic biopsy. FDOPA-PET/MRI was performed prior to surgery, allowing for precise co-registration of PET, MR, and biopsies. The biopsy sites were modeled as 5-mm spheres, and the local FDOPA uptake at each site was determined. Correlations were performed between measures of tumor histopathology, and static and dynamic PET values: standardized uptake values (SUVs), tumor to brain ratios, metabolic tumor volumes, and tracer kinetics at volumes of interest (VOIs) and biopsy sites. Results Tumor FDOPA-PET uptake was visualized in 8 patients. In 2 patients, tracer uptake was similar to normal brain reference with no histological findings of malignancy. Eight biopsy sites confirmed for glioma had FDOPA uptake without T1 contrast enhancement. The PET parameters were highly correlated only with the cell proliferation marker, Ki-67 (SUVmax: r = 0.985, P = .002). In this study, no statistically significant difference between high-grade and low-grade tumors was demonstrated. The dynamic PET analysis of VOIs and biopsy sites showed decreasing time-activity curves patterns. FDOPA-PET imaging directly influenced patient management. Conclusions Simultaneous FDOPA-PET/MRI allowed for more accurate visualization and delineation of gliomas, enabling more appropriate patient management and simplified validation of PET findings with histopathology.


2020 ◽  
pp. jclinpath-2020-206868
Author(s):  
Wei Sang ◽  
Jing Xue ◽  
Li-Ping Su ◽  
Abulajiang Gulinar ◽  
Qian Wang ◽  
...  

AimsA growing research demonstrated that YAP1 played important roles in gliomagenesis. We explored the expression of YAP1 and STAT3, the relationship between them and the effect of YAP1, STAT3 on prognosis in glioma.MethodsExpression of YAP1, p-YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 in 141 cases of low-grade gliomas (LGG) and 74 cases of high-grade gliomas (HGG) of surgical specimens were measured by immunohistochemistry. Pearson’s X2 test was used to determine the correlation between immunohistochemical expressions and clinicopathological parameters. Pearson’s or Spearman correlation test was used to determine the association between these proteins expression. Survival analysis was used to investigate the effect of these proteins on prognosis.ResultsHigh expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in HGG compared with LGG (p=0.000). High expressions of YAP1, STAT3, pSTAT3-S727 and pSTAT3-Y705 were found in 63.5%, 59.5%, 66.2% and 31.1% cases of HGG, respectively. YAP1 expression was associated to tumour location, Ki-67 and P53, STAT3 expression was related with Ki-67 and P53, and the expression of pSTAT3-S727 was associated with Ki-67. There was a significantly positive correlation between YAP1 and pSTAT3-S727 (p<0.0001; r=0.5663). Survival analysis revealed that patients with YAP1 and pSTAT3-S727 coexpression had worse overall survival (OS) and progression-free survival (PFS) (p<0.0001). Tumour grade, age, Ki-67 and YAP1 expression were independent prognostic factors for OS. In LGG group, both YAP1 and pSTAT3-S727 expressions were negative correlation with IDH1 mutation, YAP1 and pSTAT3-S727 coexpression showed worse OS and PFS of glioma patients.ConclusionOur research showed that YAP1 and STAT3 were significantly activated in HGG compared with LGG. YAP1 significantly correlated with pSTAT3-S727 in glioma, YAP1 and pSTAT3-S727 coexpression may serve as a reliable prognostic biomarker and therapeutic target for glioma.


2011 ◽  
Vol 115 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Pablo A. Valdés ◽  
Frederic Leblond ◽  
Anthony Kim ◽  
Brent T. Harris ◽  
Brian C. Wilson ◽  
...  

Object Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following δ-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies. Methods The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board–approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo. Results A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon's visual perception were classified correctly in an analysis of all tumors. Conclusions These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of intracranial tumors.


2020 ◽  
Author(s):  
Jing Zhang ◽  
Yan Xiao Chen ◽  
Jun Zi Qian ◽  
Ping Yue ◽  
Jialei Wang ◽  
...  

Abstract Background: Pulmonary mucoepidermoid carcinoma is a rare tumor of the lung. The clinicopathological characteristics of pulmonary mucoepidermoid carcinoma are not well defined due to the low incidence. This study was performed to provide more supplementary clues for the identification and understanding of pulmonary mucoepidermoid carcinoma. Methods: We reviewed the medical records since January 1, 2000 to December 31, 2018. The patients’ medical records,including age at the time of diagnosis , gender, smoking history, preoperative evaluations, operative procedures, tumor location, tumor size, tumor stage, lymph node metastasis, pathological markers, prognosis and survival information were extracted and reviewed. Categorical variables were presented as parameters and percentages. A comparison was performed between patients with high and low grade of pulmonary mucoepidermoid carcinoma. Results: 20 patients were identified and the age span is from 18 to 67 year-old with the average age is 45. Mucoepidermoid carcinomas were commonly found in men(60%). 80% patients had clinical presentations and the positive rate of tumor markers was 78%, although no specific tumor markers were found. TTF-1 were negative in all cases. ALK rearrangement was identified in a non-smoking woman with high grade pulmonary mucoepidermoid carcinoma. Surgery is the main procedure. 3-year survival rate is 72% and 80% patients achieved disease-free alive. High-grade patients tend to harbor older age (p=0.035), larger tumor volume (p=0.026) and higher index of ki-67(p=0.0005). Conclusions: Pulmonary mucoepidermoid carcinoma could occur in a wide age span. Early diagnosis and complete surgical resection may promise a good prognosis. Grading is a key factor to predict the overall survival time. Combined TTF-1 and MAML2 will benefit the identification of pulmonary mucoepidermoid carcinoma from other lung tumors. Future prospective randomized controlled trials and larger, multi-centric series are needed.


2013 ◽  
Vol 50 (2) ◽  
pp. 141-147
Author(s):  
Adriana Vaz SAFATLE-RIBEIRO ◽  
Kátia Adriana Tessima FRANCO ◽  
Carlos Eduardo Pereira CORBETT ◽  
Kiyoshi IRIYA ◽  
Bruno ZILBERSTEIN ◽  
...  

Context Gastric adenoma is a precursor lesion of the adenocarcinoma. Objective To characterize gastric adenomas according to the mucin immunoexpression and to evaluate the immunoexpression of p53, p16ink4a, BCL-2, cyclin D, Ki-67, in the adenoma and in the gastric mucosa harboring adenoma. Methods Forty gastric specimens from 20 patients were classified as intestinal (MUC2 - goblet cell mucin) or foveolar (MUC5AC - gastric-foveolar mucin) adenomas. Immunohistochemistry was performed using streptavidin-biotin-complex method. Results Twelve (60%) patients were men. The mean age was 67.9 ± 12.9 years-old. Intestinal adenomas were detected in 13 (65%) patients and gastric type in 7 (35%). Low-grade dysplasia was present in 13 (65%) of the adenomas, high-grade in 3 (15%), and adenocarcinoma within the polyp in 4 (20%). Six (30%) patients had synchronous adenocarcinoma. p53 immunoexpression was observed in 6/20 (30%) of adenomas, and in 2/6 (33.3%) of synchronous tumors. There was an association between p53 immunoexpression and intestinal type of adenoma/tumor, P = 0.04. There was no association between p16ink4a, Bcl-2, cyclin D and Ki-67 and adenoma clinicopathological characteristics. Conclusion Immunohistochemistry may be useful to classify the adenomas subtypes and may define the pathway of adenoma to carcinoma sequence.


2020 ◽  
Author(s):  
S.-Y. JING ◽  
L. CHEN ◽  
S. HAN ◽  
N. LIU ◽  
M.-Y. HAN ◽  
...  

Abstract Background: TCF7L2 gene is known as transcription factor 7-like 2 which has been identified as a novel transcription factor epithelial-mesenchymal transition (EMT) in tumor cells at 10q25.3. TCF7L2 may affect cancer progression and plays a central role in cancer proliferation, migration and invasion. However, its clinical and prognostic value have not been researched in glioma. The purpose of our study was to research TCF7L2 expression and evaluate the clinical value of prognosis.Method: We collected glioma specimens including low-grade glioma (n=46)and glioblastoma (n=51) from September 2015 to September 2017.Expression of TCF7L2 in 97 specimens were detected by quantitative real-time PCR (qRT-PCR).The chi-square test was applied to analyze the relationship between TCF7L2 expression and clinicopathological characteristics. The overall survival (OS) was analyzed by binary logistic regression analysis, the survival curves were drew by Kaplan-Meier. Univariate and multivariate analysis were utilized to analyze the relationship between prognosis and clinicopathological characteristics including TCF7L2 expression.RESULTS: Compared with low-grade glioma group, the expression of TCF7L2 was significantly increased (p<0.05). TCF7L2 overexpression was associated with large tumor volume (p=0.03), higher WHO grade (p=0.001), and recurrence (p=0.001). Moreover, Kaplan-Meier analysis proved that overexpressed TCF7L2 was related with poor OS (p< 0.05).The multivariate analysis suggested that TCF7L2 expression was an independent prognostic factor.CONCLUSIONS: Our research proved that TCF7L2 was over- expressed in glioblastoma, and, related with tumor prognosis, which, therefore, could be an independent prognostic factor for glioma patients.


2021 ◽  
pp. 34-48
Author(s):  
T. Yu. Skvortsova ◽  
Zh. I. Savintceva ◽  
D. V. Zakhs ◽  
A. F. Gurchin ◽  
A. I. Kholyavin ◽  
...  

The purpose of the study was to explore the correlation between 11С-methionine (Met) uptake measured by combined positron emission and computed tomography (PET/CT) in newly diagnosed cerebral gliomas and tumor proliferative activity as measured by Ki-67 labeling index (Ki-67 LI).The results of PET/CT with 11С-methionine (PET-Met) of 236 adult patients with pretreated glial brain tumors were included in retrospective analysis. The final diagnosis of glioma according to WHO classification of CNS tumors (2007) was based on both histology and immunohistochemistry using Ki-67 antibodies. On PET-Met tumor-to normal brain uptake ratio (TBR) was calculated by dividing maximum Met uptake in the tumor (hot spot 10 mm in diameter) to activity concentration in the contralateral cortex. The Spearmen rank correlation test was used to analyze the relationships between TBR and Ki-67 LI.PET-Met analysis showed that TBR increases with an increase in the aggressiveness of the glial tumor. The differences of TBR values between gliomas grade II vs III and grade III vs IV were significant (p < 0,001). Among grades II-III gliomas Met uptake was significantly higher in oligodendroglial and mixed gliomas than in astrocytomas (p < 0,001), but the differences did not depend on Ki-67 LI.Correlation analysis demonstrated significant correlation between Ki-67 LI and TBR values (r = 0,49, p < 0,05, Spearman rank test). With analyzing glioma subgroups TBR values correlated with Ki-67 LI in diffuse astrocytomas (r = 0,52, p < 0,05), oligodendrogliomas (r = 0,40, p < 0,05), oligoastrocytomas (r = 0,47, p < 0,05) and in high-grade gliomas (r = 0,45, p < 0,05) but not in low-grade gliomas. Comparison between TBR value and Ki-67 LI in each glioma showed a lack of coincidence in 22 % of cases (high Met uptake but low Ki-67 LI and vice versa). The main reasons for such discrepancies were tumor molecular biology or incorrect biopsy target.Met uptake in diffuse gliomas correlates with proliferative activity which justifies the use of PET-Met for glioma grading. In case of mismatch between two biomarkers one should rely on the indicator that implies a higher aggressiveness of the glioma.


Author(s):  
T. Yu. Pogorеlaya ◽  
N. F. Shchurov

Current treatment regimens for patients with breast cancer should consider molecular genetic type of tumor. To identify aggressive tumors in medical practice assess the proliferation marker Ki-67 and apoptosis marker p53, but there are no data about its prognostic value in patients BLBC living in the south-east ofUkraine. For low-grade tumors, which include BLBC, characterized by a high degree of mitotic activity. In patients with BLBC in more than 50 % cases there was detected infiltrating ductal carcinoma. The high degree of aggression BLBC in the south-east ofUkraineputs its study on a par with the major problems in oncoecology.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shiyuan Jing ◽  
Lei Chen ◽  
Song Han ◽  
Ning Liu ◽  
MingYang Han ◽  
...  

Background: The TCF7L2 gene is known as transcription factor 7-like 2 which has been identified as a novel transcription factor epithelial-mesenchymal transition (EMT) in tumor cells at 10q25.3. TCF7L2 may affect cancer progression and plays a central role in cancer proliferation, migration, and invasion. However, its clinical and prognostic value have not been researched in glioma. The purpose of our study was to research TCF7L2 expression and evaluate the clinical value of prognosis.Method: We collected glioma specimens including low-grade glioma (n = 46) and glioblastoma (n = 51) from September 2015 to September 2017. Expression of TCF7L2 in 97 specimens was detected by quantitative real-time PCR (qRT-PCR). The chi-square test was applied to analyze the relationship between TCF7L2 expression and clinicopathological characteristics. The overall survival (OS) was estimated by log-rank tests among strata, and the survival curves were drawn by Kaplan-Meier. Univariate and multivariate analysis were utilized to analyze the relationship between prognosis and clinicopathological characteristics including TCF7L2 expression.Results: Compared with the low-grade glioma group, the expression of TCF7L2 was significantly increased in the glioblastoma group (p = 0.001). TCF7L2 overexpression was associated with higher WHO grade (p = 0.001), isocitrate dehydrogenase (IDH) wild-type (p = 0.001), and lack of O(6)-methylguanine-DNA methyltransferase (MGMT) methylation (p = 0.001). Moreover, Kaplan-Meier analysis proved that overexpressed TCF7L2 was associated with poor OS (p = 0.010). The multivariate analysis suggested that TCF7L2 expression was an independent prognostic factor (p = 0.020).Conclusions: Our research proved that TCF7L2 was overexpressed in glioblastoma, and related with tumor long-term prognosis, which, therefore, could be an independent prognostic factor for glioma patients.


2021 ◽  
Vol 8 (1) ◽  
pp. 39-44
Author(s):  
Hacer Demir ◽  
İsmail Beypınar

Objective: Systemic immune inflammation index, which is one of the systemic inflammatory markers obtained by using peripheral blood cells, neutrophils, lymphocyte and platelet counts, has been previously shown to be prognostic in many types of cancer, and it has been also shown in previous studies that SII was associated with prognosis in patients who received adjuvant and neoadjuvant therapy in breast cancer. In our study, the evaluation of the potential prognostic importance of SII in patients with breast cancer diagnosed before the age of 40 was aimed. Material and method: For the study, demographic, histopathological, clinical and file data of 129 patients who were diagnosed with breast cancer in the tertiary medical oncology outpatient clinic and were 40 years old and younger at the time of diagnosis were recorded retrospectively. SII was calculated according to the neutrophil count x platelet number/lymphocyte (NxP / L) formula, and those below the optimal cut-off value obtained by ROC analysis were classified as low SII, and those above it as High SII. The relationship between breast cancer clinicopathological variables and SII was evaluated by Chi-Square test. While the effect of SII on survival was evaluated by Kaplan Meiermethod, the Logrank test was used to evaluate survival in low and high groups. Results: For the study, 1400 patients diagnosed with breast cancer were reviewed and 129 patients who were under the age of 40 at the time of diagnosis were included. Patients who had insufficient follow-up or whose pre-treatment hemogram values could not be reached, who had medication use that could affect their hemogram parameters, and those with inflammatory diseases were not included. The median age in the study was 35, and the youngest patient was 21 years old. In the study group, based on the SII cut-off value of 720 calculated according to the roc analysis, 73 patients were in the low SII group and 56 patients were in the high SII group. When the relationship between prognostic factors of the patients and SII was examined, no statistically significant relationship was observed between age, hormone receptor status, Her-2 status, histological subtype, clinical stage, grade, Ki 67 status, lymph node involvement and SII. However, in the survival analysis, although the median value could not be reached between the two groups, there was a significant difference in overall survival with SII (p = 0.051) and it was observed that survival was worse in the high SII group, and the 3 and 5-year survival rates were worse in the high group compared to the low ones. Conclusion: In our study, we reached the conclusion that SII can be an independent prognostic factor for survival in patients with breast cancer diagnosed at 40 years of age or younger. Considering the SII status together with other prognostic factors in diagnosis, a more intensive treatment plan can be made for the patients. However, well-designed prospective studies including more patients are needed for the routine use of SII.


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