CBIO-18. TP53-MUTANT OLIGODENDROGLIOMA: A SINGLE INSTITUTION CASE SERIES

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi30-vi31
Author(s):  
Mason Webb ◽  
Sani Kizilbash ◽  
Thomas Kollmeyer ◽  
Robert Jenkins ◽  
Sarah Sung ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Tp53 Mutation ◽  
Case Series ◽  
Molecular Testing ◽  
Diffuse Glioma ◽  
Who Grade ◽  
Tp53 Mutations ◽  
Grade Ii ◽  
Who Grade Iii ◽  
Grade Iii

Abstract TP53 mutations are frequent in IDH-mutant astrocytomas but unusual in oligodendroglioma and the clinical significance of TP53 mutations in oligodendroglioma are not well characterized. We reviewed genetically defined oligodendroglioma (i.e., IDH-mutant, whole-arm 1p/19q-codeleted diffuse glioma) cases that were molecularly profiled (2017-2020) at our institution and identified 7 cases with TP53 mutation (9%; n=76). Molecular testing was performed using targeted neuro-oncology NGS panel (50-gene mutation and/or 187-gene mutation/rearrangement) and OncoScan™ microarray. Four (of 7) patients were female. Median age at diagnosis was 43 years (range, 23-63). Most common presenting symptom was seizures (3 of 7). All tumors were supratentorial. Histologically, 3 tumors were WHO grade II and 4 were WHO grade III. Two (of 3) patients with a WHO grade II tumor underwent biopsy and radiotherapy at diagnosis followed by temozolomide at recurrence (progression at 67 and 157 months after diagnosis; overall survival of 124 and 201 months). Three (of 4) patients with a WHO grade III tumor were diagnosed within the last two years and are currently progression-free after standard therapy. Molecularly, in addition to TP53 mutation(s), all cases had an IDH1 and TERT promoter mutation as well as other gene mutation(s) including FUBP1 (n=5), SETD2 (n=4), PIK3R1 (n=4), PIK3CA (n=3), NF1 (n=3) and CIC (n=3). In 3 (of 7) cases, the mutational profile with high mutation count enriched for C >T/G >A transitions was highly suggestive of a hypermutation phenotype (2 cases were recurrent tumors treated with temozolomide; a recurrent and a treatment-naïve tumor had mismatch repair gene mutation). Five (of 7) cases, including the 3 hypermutant cases, lacked functional TP53 (1 case with 2 mutations, 2 cases with 1 mutation plus loss of other copy, 2 cases with 1 mutation plus copy neutral loss-of-heterozygosity). TP53 mutations are uncommon in oligodendroglioma and appear enriched in hypermutant tumors.

scholarly journals The Expression of Progesterone Receptors in Meningiomas of Different Grades

2019 ◽  
Vol 8 (2) ◽  
pp. 65-69
Author(s):  
Mohammad Tahir ◽  
Tehreem Atif ◽  
Summaya Sohail ◽  
Arfa Nawazish ◽  
Huma Mushtaq
Keyword(s):  
Progesterone Receptor ◽  
Treatment Options ◽  
Progesterone Receptors ◽  
Lower Grade ◽  
Immunoperoxidase Method ◽  
Nuclear Staining ◽  
Who Grade ◽  
Grade Ii ◽  
Who Grade Iii ◽  
Grade Iii

Background: Meningiomas are slow growing intracranial and intraspinal neoplasms with a tendency to recur locally. WHO grades them as I (benign), II (atypical) and III (anaplastic) in order of their increasing aggressiveness, based on histological parameters and brain parenchymal invasion. Progesterone receptors (PR) are more prevalent amongst the lower grade meningiomas. The objective of this study was to determine the immunohistochemical expression of progesterone receptors in meningiomas of different grades.Material and Methods: A total of 100 cases were selected over a period of 2.5 years. Three to five microns’ thick sections stained with Hematoxylin and Eosin were examined microscopically by a team of two Histopathologists and graded into grades I, II and III, according to 2016 WHO classification criteria. Another section of the original tumor was stained with progesterone receptor antibody using the conventional immunoperoxidase method. Stained slides were than examined by the same team of Histopathologists and declared positive (if nuclear staining was observed in more than 10% of tumor cells) or negative. Statistical analysis was done using SPSS version 21.Results: Out of a total of 100 cases of meningioma, there were 79 cases of benign/typical WHO grade I, 15 cases of atypical/ WHO grade II and 6 cases of anaplastic/ WHO grade III tumor. PR status was positive in 89.8 % (71/79) of grade I meningiomas and 46.6 % (7/15) of grade II/Atypical meningiomas. The 06 cases of Anaplastic/WHO grade III tumors were negative for PR. There was a higher prevalence of Progesterone receptors in female patients (89.8%; 53/59) as compared to male meningioma patients (60.9%; 25/41).Conclusion: We observed a decreased expression of progesterone receptor in higher grades of meningioma in this study. It is an effort to explore conservative treatment options for inoperable lesions, as anti-progesterone therapy may hold a promise as a new treatment option in the near future.

The role of radiosurgery in the management of WHO Grade II and III intracranial meningiomas

2013 ◽  
Vol 35 (6) ◽  
pp. E16 ◽  
Author(s):  
Dale Ding ◽  
Robert M. Starke ◽  
John Hantzmon ◽  
Chun-Po Yen ◽  
Brian J. Williams ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Stereotactic Radiosurgery ◽  
Case Reports ◽  
Case Series ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Who Grade ◽  
Intracranial Meningiomas ◽  
Grade Ii ◽  
Grade Iii

Object WHO Grade II and III intracranial meningiomas are uncommon, but they portend a significantly worse prognosis than their benign Grade I counterparts. The mainstay of current management is resection to obtain cytoreduction and histological tissue diagnosis. The timing and benefit of postoperative fractionated external beam radiation therapy and stereotactic radiosurgery remain controversial. The authors review the stereotactic radiosurgery outcomes for Grade II and III meningiomas. Methods A comprehensive literature search was performed using PubMed to identify all radiosurgery series reporting the treatment outcomes for Grade II and III meningiomas. Case reports and case series involving fewer than 10 patients were excluded. Results From 1998 to 2013, 19 radiosurgery series were published in which 647 Grade II and III meningiomas were treated. Median tumor volumes were 2.2–14.6 cm3. The median margin doses were 14–21 Gy, although generally the margin doses for Grade II meningiomas were 16–20 Gy and the margin doses for Grade III meningiomas were 18–22 Gy. The median 5-year PFS was 59% for Grade II tumors and 13% for Grade III tumors, which may have been affected by patient age, prior radiation therapy, tumor volume, and radiosurgical dose and timing. The median complication rate following radiosurgery was 8%. Conclusions The current data for radiosurgery suggest that it has a role in the management of residual or recurrent Grade II and III meningiomas. However, better studies are needed to fully define this role. Due to the relatively low prevalence of these tumors, it is unlikely that prospective studies will be feasible. As such, well-designed retrospective analyses may improve our understanding of the effect of radiosurgery on tumor recurrence and patient survival and the incidence and impact of treatment-induced complications.

The concept of the “Hexahedron” in the supratotal resection of the frontal gliomas: A technical note

2021 ◽  
Author(s):  
Pu Cai ◽  
Gang Bai ◽  
Jun Peng ◽  
Yun Li ◽  
Shanli Che ◽  
...  
Keyword(s):  
Tumour Volume ◽  
Extent Of Resection ◽  
Technical Note ◽  
Subtotal Resection ◽  
Diffuse Astrocytoma ◽  
Who Grade ◽  
Grade Ii ◽  
Supratotal Resection ◽  
Who Grade Iii ◽  
Grade Iii

Abstract OBJECTIVE To evaluate the value of the concept of the “Hexahedron” in the supratotal resection (SPTR) of frontal gliomas in both dominant and nondominant hemispheres . METHODS All consecutive patients who underwent SPTR for frontal gliomas under the guidance from the concept of the “Hexahedron” were retrospectively analysed for lesion location, pathology, extent of resection (EOR), and complications from May 2020 to June 2021. Volumetric EOR was measured and classified as SPTR, (in which the volume of the postoperative cavity was larger than the preoperative tumour volume), gross total resection (GTR, > 95% by volume) or subtotal resection (STR, ≤ 95% by volume) after independent radiological review. RESULTS Six men and two women (mean age: 47.13 years; range: 26–69 years) were included. All eight patients underwent frontal craniotomy combined frontotemporal craniotomy for resection of frontal gliomas. Neuropathological examination confirmed a diagnosis of glioblastoma WHO Grade IV in 4 patients, anaplastic oligodendroglioma WHO Grade III in 1, anaplastic astrocytoma WHO Grade III in 2 and diffuse astrocytoma WHO Grade II in 1. SPTR was achieved in six patients and STR was achieved in two. The main postoperative complications were contralateral paresis in 2 patients and memory disturbances in 1 patient. There were no cases of rebleeding or secondary operation during hospitalization. CONCLUSIONS In the presented eight cases the concept of the “Hexahedron” allowed for safe surgical supratotal resection of frontal gliomas.

P14.36 Characterising Meningiomas in young patients under 40

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii45-ii46
Author(s):  
M Attia ◽  
Y Mirkin ◽  
R Hershkovitch ◽  
Z R Cohen ◽  
Z Zibly ◽  
...  
Keyword(s):  
Skull Base ◽  
Medical Center ◽  
Young Patients ◽  
Case Series ◽  
Population Level ◽  
Who Grade ◽  
Younger Patients ◽  
Grade Ii ◽  
Grade Iii

Abstract BACKGROUND Meningiomas are the most common primary CNS tumor in adults, with a median age at diagnosis of 65 years and a female to male ratio of 2–3:1 (except in grade II, III meningiomas). Younger patients usually have a genetic background or history of prior radiation exposure. Based on population-level studies, approximately 80–85% of meningiomas are WHO grade I (benign), 15–18% grade II (atypical), and 1–3% grade III (anaplastic). This case series describes a single center experience of the presentation and pathology of meningiomas in patients under the age of 40. MATERIALS AND METHODS We reviewed the Sheba Medical Center Neurosurgery and radiotherapy databases containing patients who were operated on for meningioma between the years 2011–2020. Patients under 40 were selected and information from digital medical records was gathered on these patients, including pathology reports, surgical reports, clinical and radiological data, and the use of radiotherapy or medical treatments. RESULTS Of 600 patients in the database, 49 patients under 40 (8.3%) were identified and 54 tumors were reviewed (five patients were operated on for multiple meningiomas). 31 patients were female (63%); 2 were under 20 years old, 15 were age 20–29 and 32 were age 30–39 at first presentation. Seven patients had received prior radiation therapy for a childhood malignancy. 28 meningiomas were histology confirmed grade I (52%), 22 were grade II (41%), 2 were grade III (4%), and 2 (4%) were grade undetermined. 22 tumors were located in the skull base (41%) and 32 (59%) in the brain convexity. Of the skull base tumors, 16 were grade I, 5 were grade II, and one was grade III. Of the convexity tumors, 12 were grade I, 16 were grade II, and 2 were grade III. Median follow-up was 35 months, and longest follow-up time was 98 months. Six patients were treated with additional radiotherapy after surgery. CONCLUSION Our experience with meningioma patients under 40 revealed a different grade segregation than the older population, with younger patients showing a higher incidence of grade II tumors. These tumors are generally more aggressive, and require careful resection and consideration for post-surgical radiotherapy. Further validation with population based databases is required.

PATH-32. EXTENT, PATTERN, AND PROGNOSTIC VALUE OF MGMT PROMOTOR METHYLATION: DOES IT DIFFER BETWEEN GLIOBLASTOMA AND IDH-WILDTYPE/TERT-MUTATED ASTROCYTOMA?

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi122-vi122
Author(s):  
Nico Teske ◽  
Philipp Karschnia ◽  
Jonathan Weller ◽  
Sebastian Siller ◽  
Mario M Dorostkar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Sanger Sequencing ◽  
Favourable Outcome ◽  
Who Grade ◽  
Cpg Sites ◽  
Specific Pcr ◽  
Grade Ii ◽  
Radio Chemotherapy ◽  
Who Grade Iii ◽  
Grade Iii

Abstract INTRODUCTION The cIMPACT-NOW update 6 introduced glioblastoma diagnosis based on the combination of IDH-wildtype (IDHwt) status and TERT promotor mutation (pTERTmut). In glioblastoma as defined by histopathology according to the WHO 2016 classification, MGMT promotor status is associated with outcome. Whether this is also true in glioblastoma defined by molecular markers is yet unclear. METHODS We searched the institutional database for patients with: 1.) glioblastoma defined by histopathology; and 2.) IDHwt astrocytoma with pTERTmut. MGMT promotor methylation was analysed using methylation-specific PCR and Sanger sequencing of CpG sites within the MGMT promotor region. RESULTS We identified 224 patients with glioblastoma diagnosed based on histopathology, and 71 patients with IDHwt astrocytoma with pTERTmut (32 astrocytomas WHO grade II and 39 astrocytomas WHO grade III). There was no difference in the number of MGMT methylated tumors between the two groups as determined per PCR, and also neither the number nor the pattern of methylated CpG sites differed as determined per Sanger sequencing. Progression-free (PFS) and overall survival (OS) was similar between the two groups. Surgery was associated with improved overall survival in IDHwt astrocytoma with pTERTmut. In patients treated with radiochemotherapy or radiotherapy, higher numbers of methylated CpG sites were associated with favourable outcome in both groups. CONCLUSION Extent and pattern of methylated CpG sites are similar in glioblastoma and IDHwt astrocytoma with pTERTmut. In both groups, higher numbers of methylated CpG sites are associated with favourable outcome when radio/chemotherapy is administered. Surgery may form the basis for favourable outcome.

Lack of prognostic relevance of alterations in the epidermal growth factor receptor—transforming growth factor-α pathway in human astrocytic gliomas

1996 ◽  
Vol 85 (4) ◽  
pp. 634-641 ◽  
Author(s):  
Andreas Waha ◽  
Axel Baumann ◽  
Helmut K. Wolf ◽  
Rolf Fimmers ◽  
Jürgen Neumann ◽  
...  
Keyword(s):  
Growth Factor ◽  
Gene Amplification ◽  
Transforming Growth Factor ◽  
Growth Factor Receptor ◽  
Who Grade ◽  
Transforming Growth Factor Α ◽  
Grade Ii ◽  
Astrocytic Gliomas ◽  
Who Grade Iii ◽  
Grade Iii

✓ Alterations in the epidermal growth factor receptor (EGFR) and its main ligand, transforming growth factor-α (TGFα), were investigated for a possible prognostic relevance in 125 astrocytic gliomas (44 World Health Organization (WHO) Grade II, 19 WHO Grade III, and 62 WHO Grade IV tumors). The TGFα and EGFR proteins were detected immunohistochemically using monoclonal antibodies. A positive immunoreaction to TGFa was detected in 33 (75%) of 44 WHO Grade II astrocytomas, 18 (95%) of 19 WHO Grade III astrocytoma, and 50 (81%) of 62 WHO Grade IV glioblastomas. No correlation between TGFα immunoreaction and duration of survival could be found. A positive EGFR immunoreaction was detected in seven (16%) of 44 WHO Grade II astrocytomas, five (26%) of 19 WHO Grade III astrocytomas, and 32 (52%) of 62 WHO Grade IV glioblastomas. Of these gliomas, 97 (26 WHO Grade II, 17 WHO Grade III, and 54 WHO Grade IV gliomas) were examined for EGFR gene amplification using a differential polymerase chain reaction assay. Amplification of the EGFR gene was detected in none of the WHO Grade II astrocytomas, one (6%) of 17 WHO Grade III astrocytomas, and 18 (33%) of 54 WHO Grade IV glioblastomas. Twenty-two of the tumors investigated showed a positive EGFR immunoreaction without detectable gene amplification (five WHO Grade II, four WHO Grade III, and 13 WHO Grade IV tumors). Gene amplification was invariably associated with a positive EGFR immunoreaction. For the entire study group, a strong correlation between EGFR alterations (gene amplification and positive immunoreaction) and survival could be found. However, this correlation only reflected the higher percentages of cases with EGFR alterations in malignant gliomas and was not an independent prognostic factor as determined by multifactorial analysis. These data demonstrate that EGFR alterations are frequent events in astrocytic gliomas and are largely restricted to glioblastomas. However, within one tumor grade they do not provide prognostic information.

scholarly journals Indications of 5-Aminolevulinic Acid and Intraoperative MRI in Glioma Surgery: First Cases in Latin America in a Single Reference Center

2018 ◽  
Vol 37 (02) ◽  
pp. 088-094
Author(s):  
Ricardo Ramina ◽  
Erasmo Silva Júnior ◽  
Felipe Constanzo ◽  
Maurício Coelho Neto
Keyword(s):  
Aminolevulinic Acid ◽  
Complete Resection ◽  
World Health ◽  
Awake Surgery ◽  
Glioma Surgery ◽  
Who Grade ◽  
Combined Use ◽  
Grade Ii ◽  
Who Grade Iii ◽  
Grade Iii

Introduction The improvement on the extent of resection (EOR) of gliomas with the combination of 5-aminolevulinic acid (5-ALA) and intraoperative magnetic resonance imaging (iMRI) has been demonstrated in previous studies. We present our results with the combined use of 5-ALA and (iMRI) in the surgery of glial lesions. Methods A total of 64 cases of patients with intracranial gliomas who underwent image-guided surgery using 5-ALA with and without (iMRI) were reviewed. All patients underwent an early postoperative MRI to evaluate the EOR. Other intra-operative techniques (awake surgery, electrophysiological stimulation and monitoring) were also performed according to the location of the tumor. Results A total of 18 tumors did not show intraoperative 5-ALA fluorescence (according to the World Health Organization [WHO] classification of tumors, 2 WHO-grade I, 14 WHO-grade II, 1 WHO-grade III and 1 WHO-grade IV), and 46 tumors showed intraoperative 5-ALA fluorescence (3 WHO-grade II, 3 WHO-grade III, 40 WHO-grade IV). In 28 of the 46 5-ALA positive cases, a safe 5-ALA free resection was achieved. In the 5-ALA negative cases, the (iMRI) findings guided the EOR, and complete resection was achieved in 11 cases. Complete resection was opted out in gliomas infiltrating eloquent areas. Conclusions The combined use of 5-ALA and IMRI showed improved results in glioma surgery, offering the safest maximal EOR. In the 5-ALA positive cases (mostly high-grade), fluorescence was a more useful tool. In the 5- ALA negative cases (mostly low-grade), the (iMRI) was decisive to guide the EOR of the tumor.

scholarly journals Gene Expression Profiling in Human High-Grade Astrocytomas

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Zhongyu Liu ◽  
Zhiqiang Yao ◽  
Chao Li ◽  
Yicheng Lu ◽  
Chunfang Gao
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Anaplastic Astrocytoma ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Who Grade ◽  
Grade Ii ◽  
Who Grade Iii ◽  
Grade Iii

Diffuse astrocytoma of (WHO grade II) has a tendency to progress spontaneously to anaplastic astrocytoma (WHO grade III) and/or glioblastoma (WHO grade IV). However, the molecular basis of astrocytoma progression is still poorly understood. In current study, an essential initial step toward this goal is the establishment of the taxonomy of tumors on the basis of their gene expression profiles. We have used gene expression profiling, unsupervised (hierarchal cluster (HCL) and principal component analysis (PCA)) and supervised (prediction analysis for microarrays (PAM)) learning methods, to demonstrate the presence of three distinct gene expression signatures of astrocytomas (ACMs), which correspond to diffuse or low-grade astrocytoma (WHO grade II), Anaplastic astrocytoma (WHO grade III) and Glioblastoma multiforme (WHO grade IV). We also demonstrate a 171 gene-based classifier that characterize the distinction between these pathologic/molecular subsets of astrocytomas. These results further define molecular subtypes of astrocytomas and may potentially be used to define potential targets and further refine stratification approaches for therapy. In addition, this study demonstrates that combining gene expression analysis with detailed annotated pathway and gene ontology (GO) category resources was applied to highly enriched normal and tumor population; it can yield an understanding of the critical biological mechanism of astrocytomas.

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