Immunohistochemical expression of HGF and cMET in meningiomas

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Thanaa E Helal ◽  
Faten W Ragheb ◽  
Iman H Hewedi ◽  
Nermine M Abd Raboh ◽  
Mariam I Halim

Abstract Background Meningiomas are the most common intracranial neoplasm together with gliomas; but unlike gliomas they are still graded according to their histopathological picture. Many growth factors and tyrosine kinase receptors have been studied in meningiomas in an attempt for prognostic stratification of patients, also to find a suitable targeted therapy for meningiomas. Aim of the study To correlate the immunohistochemical expression of HGF and cMET with the different WHO grades of meningioma in addition to brain invasion. Materials and methods This study included 60 cases of meningiomas (WHO grade I, n = 30 and WHO grade II & III, n = 30), brain invasion was present in 14 cases. Results HGF, cMET & HGF/cMET co-expression were positive in 60.0%, 65.0% and 58.3% respectively of the cases; WHO grade I meningioma showed positivity in 30.0%, 33.3% and 30.0% of the cases respectively in contrast with 90.0%, 96.7% and 86.7% of the cases of WHO grades II & III meningiomas respectively. The relation was statistically highly significant (p- value: <0.001). As regards cases with brain invasion the expression of HGF, cMET and HGF/cMET co-expression was found in 92.9%, 100.0% and 92.9% respectively in comparison with 50.0%, 54.3% and 47.8% in the rest of the cases of meningiomas respectively; the relation was statistically significant (p- value: 0.004). Conclusion The results suggest that HGF/cMET pathway may play a role in the progression of meningiomas from WHO grade I to higher grades II & III.

2020 ◽  
Author(s):  
Giulia Berzero ◽  
Anna Luisa Di Stefano ◽  
Susanna Ronchi ◽  
Franck Bielle ◽  
Chiara Villa ◽  
...  

Abstract Background IDH-wildtype (IDHwt) grade II gliomas are a rare and heterogeneous entity. Survival and prognostic factors are poorly defined. Methods We searched retrospectively all patients diagnosed with diffuse WHO grade II and III gliomas at our center (1989-2020). Results Out of 517 grade II gliomas, 47 were “diffuse astrocytomas, IDHwt”. Tumors frequently had fronto-temporo-insular location (28/47, 60%) and infiltrative behavior. We found TERT promoter mutations (23/45, 51%), whole chromosome 7 gains (10/37, 27%), whole chromosome 10 losses (10/41, 24%), and EGFR amplifications (4/43, 9%) but no TP53 mutations (0/22, 0%). Median overall survival (OS) was 59 months (vs. 19 months for IDHwt grade III gliomas (p< 0.0001). Twenty-nine patients (29/43, 67%) met the definition of molecular glioblastoma according to cIMPACT-NOW update3. Median OS in this subset was 42 months, which was shorter compared to patients with IDHwt grade II gliomas not meeting this definition (median OS: 57 months), but substantially longer compared to IDHwt grade III gliomas meeting the definition for molecular glioblastoma (median OS: 17 months, p<0.0001). Most patients with IDHwt grade II gliomas met cIMPACT criteria because of isolated TERT promoter mutations (16/26, 62%), which were not predictive of poor outcome (median OS: 88 months). Actionable targets, including 5 gene fusions involving FGFR3, were found in 7 patients (24%). Conclusions Our findings highlight the importance of histological grading and molecular profiling for the prognostic stratification of IDHwt gliomas and suggest some caution when assimilating IDHwt grade II gliomas to molecular glioblastomas, especially those with isolated TERT promoter mutation.


2010 ◽  
Vol 134 (5) ◽  
pp. 766-770 ◽  
Author(s):  
Deepali Jain ◽  
Katayoon B. Ebrahimi ◽  
Neil R. Miller ◽  
Charles G. Eberhart

Abstract Context.—Meningiomas represent approximately 4% of all intraorbital tumors and can arise from the optic nerve or extend into the orbit from adjacent structures. Objective.—To examine a cohort of intraorbital meningiomas and use the current World Health Organization (WHO) scheme to assess the effect of changes to the classification of tumors at this site. Design.—The histopathology and clinical findings of intraorbital meningiomas resected between 1968 and 2008 at our institution were reviewed according to the WHO 2007 classification scheme. Results.—A total of 51 intraorbital meningiomas were reviewed. The mean age at presentation was 45 years, but 5 tumors arose in children. Two patients were known to have neurofibromatosis type 2, and 1 had inherited retinoblastoma. Orbital meningiomas were more frequently encountered in women (30 cases) than in men (21 cases). In 21 patients, the tumor was associated with the optic nerve. The most common (25 of 51 tumors; 49%) histopathologic subtype was meningothelial. Most (47 of 51; 92%) of the tumors were WHO grade I. Four tumors (8%) were WHO grade II, with 4 or more mitotic figures per 10 high-power fields, brain invasion, chordoid histology, or a combination of these features. Conclusions.—Intraorbital meningiomas were most frequently of the meningothelial or transitional subtypes and were WHO grade I. One relatively common intracranial subtype, fibrous meningioma, was not encountered. The percentage of WHO grade II tumors in the orbit (8%) is similar to that reported for intracranial tumors using the current grading scheme.


2021 ◽  
Vol 42 (06) ◽  
pp. 569-576
Author(s):  
Ramya Lakshmi Veduruvada ◽  
Megha S. Uppin ◽  
Meher Lakshmi Konatam ◽  
Rajesh Alugolu ◽  
Vamsi Krishna Yeramneni ◽  
...  

Abstract Introduction Astrocytomas are the most common gliomas, classified on the basis of grade and IDH mutation status according to the World Health Organization (WHO) 2016 update. IDH mutations are seen in 70 to 80% of diffuse grade II and III astrocytomas and are associated with better outcome. They serve as predictive biomarker in IDH-targeted therapies such as small-molecule inhibitors or vaccines. Objective The aim of this study was to analyze the clinical, morphological, immunohistochemical, and molecular genetic characteristics of diffuse astrocytoma (DA: grades II and III). The IDH mutant and wild-type tumors are compared and contrasted with survival analysis on follow-up. Materials and Methods This was a retrospective study conducted on surgically resected tumor specimens. The hematoxylin and eosin-stained slides were examined for histologic features. Immunohistochemistry (IHC) was performed using IDH1R132H, ATRX, p53, and Ki67. All cases of negative immunohistochemical expression of IDH1R132H were subjected to IDH1 mutation analysis by Sanger sequencing. Overall survival was estimated by the Kaplan-Meier method using the log-rank (Mantel–Cox) test. Results The study included 51 cases of DA in the age of 17 to 66 years, mean ± standard deviation was 35.5 ± 9.7 years, and male:female ratio was 2:1.The IDH1R132H cytoplasmic immunopositivity was seen in 36 cases (70.5%), of which 63.6% were of grade II and 72.5% were of grade III. ATRX showed loss of expression in 50 cases (98%), and p53 showed diffuse strong immunohistochemical expression in all the cases of IDH mutant tumors. The difference in the age at presentation for IDH mutant (32.5 years) and wild type tumors (38 years) was statistically significant. Median survival was 55.3 months and 22.2 months in of IDH mutant and wild type cases, respectively. Conclusion IHC and sequencing for IDH mutations is helpful in making an integrated diagnosis and classifying definite molecular subgroups of astrocytic tumors. Mutations in IDH core-elate with survival. IDH mutant tumors showed longer survival duration and are good prognostic indicators.


2002 ◽  
Vol 43 (5) ◽  
pp. 474-482 ◽  
Author(s):  
W. Reiche ◽  
I. Grunwald ◽  
K. Hermann ◽  
M. Deinzer ◽  
W. Reith

Purpose: To study the pattern of contrast enhancement in MR and CT of oligodendrogliomas and to compare this with other imaging findings and with histopathological grading criteria. Material and Methods: 20 patients with oligodendrogliomas (12 low-grade WHO II and 8 anaplastic WHO III) were reviewed. 20 complete MR investigations, 20 non-enhanced CT studies and 16 CTs after contrast enhancement were estimated blindly without knowledge of the tumour histological grades. Results: All anaplastic oligodendrogliomas showed tumour contrast enhancement on MR and CT images. Also in 6/12 low-grade oligodendrogliomas the contrast was enhanced on MR imaging. In 5 of these, tumour calcifications were detected by CT. The remaining 6/12 WHO grade II cases showed no significant MR contrast enhancement. Of the oligodendrogliomas grade II, CT showed contrast uptake in 3 cases and no enhancement in 6, while in 3 cases postcontrast CT was not available. A comparison of contrast enhancement with tumour grade resulted in a p-value of 0.042 for MR and of 0.011 for CT. A combined statistical test of tumour grade and calcifications detected by CT compared with MR contrast enhancement showed a significant correlation ( p=0.014). Conclusion: These data demonstrated that a clear grading of oligodendrogliomas based on the image criterion MR contrast enhancement was not possible. We suppose that, besides tumour neovascularisation, additional factors such as calcifications may disturb the blood-brain barrier.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ning Li ◽  
Yan Mo ◽  
Chencui Huang ◽  
Kai Han ◽  
Mengna He ◽  
...  

BackgroundBrain invasion in meningioma has independent associations with increased risks of tumor progression, lesion recurrence, and poor prognosis. Therefore, this study aimed to construct a model for predicting brain invasion in WHO grade II meningioma by using preoperative MRI.MethodsOne hundred seventy-three patients with brain invasion and 111 patients without brain invasion were included. Three mainstream features, namely, traditional semantic features and radiomics features from tumor and tumor-to-brain interface regions, were acquired. Predictive models correspondingly constructed on each feature set or joint feature set were constructed.ResultsTraditional semantic findings, e.g., peritumoral edema and other four features, had comparable performance in predicting brain invasion with each radiomics feature set. By taking advantage of semantic features and radiomics features from tumoral and tumor-to-brain interface regions, an integrated nomogram that quantifies the risk factor of each selected feature was constructed and had the best performance in predicting brain invasion (area under the curve values were 0.905 in the training set and 0.895 in the test set).ConclusionsThis study provided a clinically available and promising approach to predict brain invasion in WHO grade II meningiomas by using preoperative MRI.


2020 ◽  
Vol 10 (1) ◽  
pp. 3-5
Author(s):  
Parometa Barma ◽  
Ibrahim Khalil ◽  
Tanzima Yeasmin

Developing country like Bangladesh among 90% of oral malignant neoplasm are arising from squamous layer of oral epithelium which are third leading of this country with severe disfiguration, functiolaesa, psychological impairments and socio-economic hardship. In this study we found the prevalence of OSCC was 6.5% among total cancer patients in the two tertiary level hospitals of Bogura. Male (70%) are affected more than in females (30%). In response to male and female parameter, sex distribution ratio was 2.3:1. The prevalent average age was 55.40 years. About 80% of ulcer site was buccal mucosa then 10 % were lip mucosa. About 80% people were habituated by betel nut, leaf with tobacco chewers. Moreover 46.7% of them were maltreated by quack doctors before. Majority of the patient was in Grade II (56.7%). Correlation between variable in respect of age and cancer grading was explained. According to these study OSCC patients in north bangle region like Bogura was quite high on ( significant p-value ≤ 0.05). Description of oral squamous cell carcinoma on the basis of demographic and clinical profile was the major aim . Most of the cases report with intermediate grade of the disease which often leads to decrease the chance of survival of a patient. So new strategies should be considered to overcome the present situation must be undertaken by oral health programs for the early diagnosis and prevention, build up awareness and management and follow up of oral cancer. Update Dent. Coll. j: 2020; 10 (1): 3-5


2021 ◽  
Vol 52 (2) ◽  
pp. 233-243
Author(s):  
Simon Bernatz ◽  
Daniel Monden ◽  
Florian Gessler ◽  
Tijana Radic ◽  
Elke Hattingen ◽  
...  

AbstractHigher grade meningiomas tend to recur. We aimed to evaluate protein levels of vascular endothelial growth factor (VEGF)-A with the VEGF-receptors 1-3 and the co-receptors Neuropilin (NRP)-1 and -2 in WHO grade II and III meningiomas to elucidate the rationale for targeted treatments. We investigated 232 specimens of 147 patients suffering from cranial meningioma, including recurrent tumors. Immunohistochemistry for VEGF-A, VEGFR-1-3, and NRP-1/-2 was performed on tissue micro arrays. We applied a semiquantitative score (staining intensity x frequency). VEGF-A, VEGFR-1-3, and NRP-1 were heterogeneously expressed. NRP-2 was mainly absent. We demonstrated a significant increase of VEGF-A levels on tumor cells in WHO grade III meningiomas (p = 0.0098). We found a positive correlation between expression levels of VEGF-A and VEGFR-1 on tumor cells and vessels (p < 0.0001). In addition, there was a positive correlation of VEGF-A and VEGFR-3 expression on tumor vessels (p = 0.0034). VEGFR-2 expression was positively associated with progression-free survival (p = 0.0340). VEGF-A on tumor cells was negatively correlated with overall survival (p = 0.0084). The VEGF-A-driven system of tumor angiogenesis might still present a suitable target for adjuvant therapy in malignant meningioma disease. However, its role in malignant tumor progression may not be as crucial as expected. The value of comprehensive testing of the ligand and all receptors prior to administration of anti-angiogenic therapy needs to be evaluated in clinical trials.


Author(s):  
Pranay Soni ◽  
Jianning Shao ◽  
Arbaz Momin ◽  
Diana Lopez ◽  
Lilyana Angelov ◽  
...  

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 342 ◽  
Author(s):  
Enrico Franceschi ◽  
Dario De Biase ◽  
Vincenzo Di Nunno ◽  
Annalisa Pession ◽  
Alicia Tosoni ◽  
...  

Background: Non-canonical mutations of the isocitrate dehydrogenase (IDH) genes have been described in about 20–25% and 5–12% of patients with WHO grade II and III gliomas, respectively. To date, the prognostic value of these rare mutations is still a topic of debate. Methods: We selected patients with WHO grade II and III gliomas and IDH1 mutations with available tissue samples for next-generation sequencing. The clinical outcomes and baseline behaviors of patients with canonical IDH1 R132H and non-canonical IDH1 mutations were compared. Results: We evaluated 433 patients harboring IDH1 mutations. Three hundred and ninety patients (90.1%) had a canonical IDH1 R132H mutation while 43 patients (9.9%) had a non-canonical IDH1 mutation. Compared to those with the IDH1 canonical mutation, patients with non-canonical mutations were younger (p < 0.001) and less frequently presented the 1p19q codeletion (p = 0.017). Multivariate analysis confirmed that the extension of surgery (p = 0.003), the presence of the 1p19q codeletion (p = 0.001), and the presence of a non-canonical mutation (p = 0.041) were variables correlated with improved overall survival. Conclusion: the presence of non-canonical IDH1 mutations could be associated with improved survival among patients with IDH1 mutated grade II–III glioma.


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