scholarly journals Mutation Status and Epithelial Differentiation Stratify Recurrence Risk in Chordoid Meningioma—A Multicenter Study with High Prognostic Relevance

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 225 ◽  
Author(s):  
Maria-Magdalena Georgescu ◽  
Anil Nanda ◽  
Yan Li ◽  
Bret C. Mobley ◽  
Phyllis L. Faust ◽  
...  

Chordoid meningioma is a rare WHO grade II histologic variant. Its molecular alterations or their impact on patient risk stratification have not been fully explored. We performed a multicenter, clinical, histological, and genomic analysis of chordoid meningiomas from 30 patients (34 tumors), representing the largest integrated study to date. By NHERF1 microlumen immunohistochemical detection, three epithelial differentiation (ED) groups emerged: #1/fibroblastic-like, #2/epithelial-poorly-differentiated and #3/epithelial-well-differentiated. These ED groups correlated with tumor location and genetic profiling, with NF2 and chromatin remodeling gene mutations clustering in ED group #2, and TRAF7 mutations segregating in ED group #3. Mutations in LRP1B were found in the largest number of cases (36%) across ED groups #2 and #3. Pathogenic ATM and VHL germline mutations occurred in ED group #3 patients, conferring an aggressive or benign course, respectively. The recurrence rate significantly correlated with mutations in NF2, as single gene, and with mutations in chromatin remodeling and DNA damage response genes, as groups. The recurrence rate was very high in ED group #2, moderate in ED group #3, and absent in ED group #1. This study proposes guidelines for tumor recurrence risk stratification and practical considerations for patient management.

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii16-iii16
Author(s):  
M M Georgescu ◽  
Y Li ◽  
A Olar ◽  
B Mobley ◽  
P Faust ◽  
...  

Abstract BACKGROUND Meningiomas are heterogenous tumors and their pathologic classification in the WHO Classification of Tumors of the CNS comprises 13 recognized histologic variants. Chordoid meningioma is a rare and more aggressive histologic variant of meningioma. Due to paucity of cases, the molecular profiling and patient risk stratification were not addressed in this variant. MATERIAL AND METHODS We performed an integrated clinical, NHERF1 immunohistochemical (IHC) and next generation sequencing (NGS) analysis of WHO grade II chordoid meningiomas from 30 patients (35 cases), representing the largest study to date. The NGS was performed by using a custom Agilent-generated 295-gene library containing genes with recurrent mutations in adult and pediatric, primary and metastatic brain cancer. Five of these cases cases were confirmed by performing NGS at Tempus on the xT panel containing 596 genes, and an additional 10 atypical (non-chordoid) meningioma, WHO grade II, cases were sequenced at Tempus, for comparison. RESULTS The patients with chordoid meningioma have demographic characteristics different from the general population: younger age of onset (45 vs 65), skull base (SB) location for the female patients (6:1), and increased recurrence rate (25% at 5 years). NHERF1 microlumen extent directly correlated with skull base location (p=0.0002), and segregated tumors into three cell differentiation categories -fibroblastic (13.3%), epithelial/poorly-differentiated (26.7%) and epithelial/well-differentiated (60%). NGS identified NF2 and TRAF7, as the most common mutated genes, correlating with the location and epithelial differentiation of the tumors. Mutations in AKT1, KLF4 and MN1 were found in isolated well-differentiated skull base tumors. Mutations in genes not previously involved in meningioma pathogenesis were also found. CONCLUSION The integrated tumor analysis stratified the patients into: (1) HIGH RECURRENCE RISK , characterized by tumors harboring NF2 mutations and low epithelial differentiation and (2) LOW RECURRENCE RISK , characterized by tumors exhibiting either epithelial differentiation, skull base location and TRAF7/AKT1/KLF4 mutations, or fibroblastic differentiation, non-skull base location and other mutations. This is the first study of the integrated mutational landscape of chordoid meningioma with important implications for patient risk stratification and management.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4731-4731 ◽  
Author(s):  
Jeffrey Paul Liles ◽  
Christopher Wanderling ◽  
Jordan Lee Liles ◽  
Debra Hoppensteadt ◽  
Jawed Fareed ◽  
...  

Abstract Background: Oral anticoagulants such as warfarin (W) have been conventionally used for the management of atrial fibrillation (AF). Despite the effectiveness of W, its use in AF patients requiring anticoagulation is suboptimal with an even greater underuse seen in elderly patients who are at higher risk of stroke. New oral anticoagulants such as rivaroxaban (R) and apixaban (A) have been approved to manage thrombotic and cardiovascular disorders including AF. The newer anticoagulants do not require continuous monitoring like W does and are much more convenient for patients with AF. Objective: To profile the baseline level of circulating thrombogenic biomarkers von Willebrand Factor (vWF), prothrombin fragment 1.2 (F1+2), microparticle bound tissue factor (MP-TF) and plasminogen activator inhibitor (PAI-1) in patients with AF. Additionally, the effect of both newer (R and A) and traditional (W) anticoagulants on the levels of thrombogenic biomarkers in patients with AF will be assessed. Materials: Citrated blood was drawn from thirty AF patients prior to ablation surgery and spun at 3000 rpm to obtain platelet poor plasma. Normal plasma samples from healthy controls were purchased from a commercial source (George King Biomedical, Overland Park, KS). The plasma samples were analyzed using a biochip array (Randox, London, UK) for metabolic syndrome biomarkers including PAI-1 and ELISA kits for vWF, MP-TF (Hyphen BioMed, Nueville-Sur-Oise, France) and prothrombin F1+2 (Siemens, Newark, DE). Results: Circulating levels of vWF, MP-TF and PAI-1 were statistically increased in patients with AF compared to normal (P<0.0001, P<0.0001, and P=0.0014, respectively). Circulating levels of prothrombin F1+2 showed no difference between the AF and normal group (P=0.2696). AF patients (n=30) were divided into two groups based on their usage (Group 1, n=21) and non-usage (Group 2, n=9) of any anticoagulant. Furthermore, those on anticoagulants were divided based on their use of newer (R and A, Group 3, n=16) or traditional (W, Group 4, n=4) anticoagulants. A statistical increase in vWF (P<0.0001), MP-TF (P<0.0001) and PAI-1 (P=0.011) remained in Group 1 compared to normal while a statistical increase in prothrombin F1+2 (P=0.0343) and PAI-1 (P=0.0040) were noted in Group 2 compared to normal. vWF (P=0.0036) and MP-TF (P=0.0059) were elevated in Group 1 compared to Group 2 while prothrombin F1+2 (P=0.0697) and PAI-1 (P=0.4548) showed no difference between the two groups. Furthermore, there was no statistical difference in the level of any thrombogenic biomarker in AF patients between Group 3 (R and A) and Group 4 (W). (Table 1) Discussion: Elevated levels of vWF, MP-TF and PAI-1 seen in AF patients compared to normal provide insight into an additional risk of thrombogenesis associated with AF which is not targeted by current anticoagulant medications. Most patients are assessed using a stroke risk stratification scale (CHA2DS2VASc, CHADS2, CHADS-VASC, or CHADS) to determine if anti-coagulants should be used to prevent stroke associated with AF. Of the 30 patients examined in this study, 8/9 (89%) patients who were not on anticoagulants had a stroke risk stratification score of 0 while 20/21(95%) patients who were on anticoagulants had a score of >1. This data supports studies which suggest that adding levels of prothrombotic biomarkers to current risk stratification scales could be more effective in assessing the risk of stroke of patients with AF. This data also suggests that although very effective in lowering prothrombin F1+2 levels in AF, the newer anticoagulants, R and A, and the traditional anticoagulant, W, still leave additional prothrombotic biomarkers unaffected. These unaffected biomarkers could be the potential target of future drug therapies which could lower the risk of stroke in patients with AF even more than the use of newer/traditional anticoagulants alone.Table 1.Biomarkers of Thrombogenesis in AF and Normal GroupsGroupvWF (concentration %)Prothrombin F1+2 (pmol/L)MP-TF (pg/mL)PAI-1 (ng/mL)Normal4140 ± 919 n=46106.1 ± 52.7 n=500.38 ± 0.25 n=483.21 ± 4.13 n=25AF Group 1 Anticoagulant n=216616 ± 1173107.9 ± 61.20.93 ± 0.715.69 ± 4.15Group 2 Non-Anticoagulant n=94788 ± 1338162.5 ± 93.30.51 ± 0.136.49 ± 3.14Group 3 New Anticoagulants (R and A) n=166721 ± 1127103.5 ± 37.60.76 ± 0.345.68 ± 4.53Group 4 Traditional Anticoagulants (W) n=46387 ± 158075.2 ± 52.60.94 ± 0.335.63 ± 3.52 Disclosures No relevant conflicts of interest to declare.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Avetis Azizyan ◽  
Paula Eboli ◽  
Doniel Drazin ◽  
James Mirocha ◽  
Marcel M. Maya ◽  
...  

Objective. To determine whether angiomatous and microcystic meningiomas which mimic high grade meningiomas based on extent of peritumoral edema can be reliably differentiated as low grade tumors using normalized apparent diffusion coefficient (ADC) values.Methods. Preoperative magnetic resonance imaging (MRI) of seventy patients with meningiomas was reviewed. Morphologically, the tumors were divided into 3 groups. Group 1 contained 12 pure microcystic, 3 pure angiomatoid and 7 mixed angiomatoid and microcystic tumors. Group 2 included World Health Organization (WHO) grade II and WHO grade III tumors, of which 28 were atypical and 9 were anaplastic meningiomas. Group 3 included WHO grade I tumors of morphology different than angiomatoid and microcystic. Peritumoral edema, normalized ADC, and cerebral blood volume (CBV) were obtained for all meningiomas.Results. Edema index of tumors in group 1 and group 2 was significantly higher than in group 3. Normalized ADC value in group 1 was higher than in group 2, but not statistically significant between groups 1 and 3. CBV values showed no significant group differences.Conclusion. A combination of peritumoral edema index and normalized ADC value is a novel approach to preoperative differentiation between true aggressive meningiomas and mimickers such as angiomatous and microcystic meningiomas.


1970 ◽  
Vol 48 (8) ◽  
pp. 1439-1443 ◽  
Author(s):  
P. Bartoš ◽  
G. J. Green ◽  
P. L. Dyck

Thirty-four European wheat cultivars were classified into eight groups according to their reactions to seven North American races of Puccinia graminis f. sp. tritici. Cultivars of seven groups were crossed with a variety or single gene line having similar rust reactions. These crosses indicated that the resistance of Hybrid 80-3, Stabil, and Vrakuňská (group 1) was conferred by stem rust resistance gene Sr5; Admonter Früh (group 2) carries Sr5 and an unidentified gene; Flevina (group 4) carries Sr11; Erythrospermum 974 (group 5) carries Sr5 and Sr8; Étoile de Choisy (group 6) carries an unidentified gene for moderate resistance to all the races used; and Mironovskaja 808 (group 7) and Belocerkovskaja 198 (group 8) each carry an unidentified gene. The five cultivars in group 3 were not studied genetically but they react like Marquis and may carry Sr7b.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2468-2468 ◽  
Author(s):  
Christian Steidl ◽  
Julie Schanz ◽  
Michelle M. Le Beau ◽  
John M. Bennett ◽  
Ulrich Germing ◽  
...  

Abstract Introduction The International Prognostic Scoring System (IPSS) for evaluating prognosis in myelodysplastic syndromes (MDS) has been the standard for risk assessment in this disease for the past ten years. Based on a patient cohort comprising 816 primary MDS patients from the IMRAW, a refined bone marrow cytogenetic classification system was introduced. Recently, the GACMSG published cytogenetic data including 1155 primary MDS patients treated with supportive care only. Coalescence of these two large databases offered the opportunity to analyze the cytogenetic data jointly and to propose a modified cytogenetic risk stratification system. Patients and Methods 1971 patients with karyotype and survival data originating from the IMRAW and the GACMSG cohorts were included in this study. The collectives comprised patients with primary MDS treated with supportive care, only allowing short courses of low dose oral chemotherapy or hemopoietic growth factors. By reviewing the ISCN karyotypes, the patients were grouped into cytogenetic categories defined by median survival (MS) (Haase et al, Blood in press). The categories comprised karyotypes with the respective abnormality alone or in combination with one additional anomaly. Karyotypes with 3, or more than 3 abnormalities were considered separate categories. Results We found 15 cytogenetic categories each comprising 10 or more patients. These categories could be combined into 4 prognostic groups according to the MS: Group 1 (MS&gt;3 years): normal karyotype, del(5q), del(12p), del(20q), +21, −Y, −X; Group 2 (1.5–3 years): +1/+1q/t(1q), add(3q)/inv(3q)/del(3q)/t(3q), +8, del(11q); Group 3 (1–1.5 years): 3 anomalies, −7, del(7q); Group 4 (MS&lt;1 year): &gt;3 anomalies. Further stratification of these categories led to a system with 4 distinct risk strata (number of patients): good (1374), int-1 (160), int-2 (99), and poor (166). Only 172 patients (9% of all patients) could not be classified according to this system. Survival analysis of these 4 groups showed distinct MS (Log-rank test: p&lt;0.0001): good, 50 months; int-1, 24 months; int-2, 15 months; poor, 6 months. When combining the non-classified patients into one group MS was 31 months. When comparing this new classification system with the original system defined by the IPSS, 66 formerly intermediate risk patients shifted into the good risk group and 114 poor risk patients into the intermediate risk group. Discussion Combined examination of the two databases introduces 7 new cytogenetic categories with distinct survival times as compared to the IPSS; Group 1: del(12p), +21, −X; Group 2: +1/+1q/t(1q), add(3q)/inv(3q)/del(3q)/t(3q), del(11q); Group 3: 3 anomalies. Based on previously published data, the proposed system combines non-complex karyotypes in one category and distinguishes karyotypes with 3 or more than 3 abnormalities. With respect to future refined integrative scoring in MDS we present an approach that distinguishes groups of intermediate risk and a heterogeneous group of as yet unclassified rare cases harboring uncertain prognoses. In the latter cases, risk assessment should be based on other prognostic parameters rather than assigning an intermediate risk to this group. This new cytogenetic risk stratification system needs to be validated and tested using multivariate approaches.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Puymirat ◽  
V Tea ◽  
F Schiele ◽  
C Baixas ◽  
X Lamit ◽  
...  

Abstract Background High dose statins prescription are strongly recommended in patients after acute myocardial infarction (AMI) in current guidelines. Aim We aimed to assess the clinical impact on major cardiovascular events (MACE) of high dose statins prescription at discharge according to the atherothrombotic risk stratification in a routine-practice population of AMI patients, and to determine the relative efficacy of currently recommended high dose statins according to risk level. Methods We used data from the 2005, and 2010 FAST-MI nationwide registries, including 7,839 patients with AMI (54% STEMI) admitted to cardiac intensive care units in France. Atherothrombotic risk stratification was performed using the TIMI Risk Score for Secondary Prevention (TRS-2P). Patients were defined in 3 categories: Group 1 (Low-risk; TRS-2P=0/1); Group 2 (Intermediate-risk; TRS-2P=2); and, Group 3 (High-risk; TRS-2P≥3). Baseline characteristics and the rate of MACE (defined as death, stroke or re-MI) at 5-years were analyzed according to TRS-2P categories, and the impact of high dose statins (i.e. atorvastatin 80mg/day or rosuvastatin 20mg/day) at discharge was compared using Cox multivariate analysis among the different risk groups. Results A total of 7,348 patients discharge alive and in whom TRS-2P was available. Prevalence of Groups 1, 2, and Group 3 was 41.5%, 25% and 33.5% respectively. Over the 5-year period, the overall risk of patients admitted for AMI decreased in Group 3 from 41% to 27% (P<0.001). Optimal medical therapy at discharge (defined by the use of dual antiplatelets therapy, statins for all; and, beta-blocker, ACE-I or ARB when appropriate) was 53% in Group 3, 67% in Group 2, and 80% in Group 1 (P<0.001). High dose statins prescription at discharge was 18.5% (Group 3), 31.3% (Group 2), and 41.3%% (Group 1). High dose statins prescription was associated with lower MACE at five-year in the overall population compared to patients with intermediate/low dose statins or without statin prescription (14.3% vs. 29.6%; Δ absolute risk= 15.3%; HR adjusted on baseline characteristics and management: 0.86, 0.76–0.97, P=0.018). The decrease in MACE at five-year was observed in all TRS-2P categories (Group 1: 8.1% vs. 10.7%, Δ= 2.6%; Group 2: 14.8% vs. 21.6%, Δ= 6.8%; Group 3: 30.8% vs. 51.6%, Δ= 20.8%). Finally, the benefits of high dose statins in low- and intermediate-risk was lower (HR=0.97; 95% CI, 0.74–1.26; P=0.81 and HR=1.06; 95% CI, 0.81–1.38; P=0.81) compared to high-risk patients (HR=0.78; 95% CI, 0.65–0.94; P=0.008). Five-year events-free survival Conclusions High dose statins prescription at discharge after AMI was associated with lower MACE at five-year regardless of the atherothrombotic risk stratification, although the highest absolute reduction was found in the high risk TRS2P class. Acknowledgement/Funding The FAST-MI 2010 registry is a registry of the French Society of Cardiology, supported by unrestricted grants from: Merck, the Eli-Lilly-Daiichi-Sanky


2018 ◽  
Vol 50 (03) ◽  
pp. 292-297 ◽  
Author(s):  
Hong-Ray Chen ◽  
Chien-Chang Kao ◽  
Chih-Wei Tsao ◽  
Shou-Hung Tang ◽  
Meng En ◽  
...  

Abstract Objective This study was performed to compare the efficacy of intravesical mitomycin C (MMC) instillation for the prophylaxis of Ta or T1 high-risk nonmuscle invasive bladder cancer (NMIBC) using different schedules. Materials and methods This retrospective cohort study was conducted on 152 patients treated with intravesical MMC from April 2009 to September 2016. The mean follow-up time was 32.67 months. All patients underwent a complete transurethral resection of bladder tumor (TURBT) and postoperative instillation of MMC within 24 h. The patients were divided into 4 treatment groups: Group 1 was followed-up without any maintenance MMC dose treatment; Group 2 received an MMC instillation once per week for the first 8 weeks; Group 3 received an MMC instillation once per week for the first 8 weeks, and once per month for the following 6 months; and Group 4 received an MMC instillation once per week for the first 8 weeks, and once per month for the following 12 months. Results The overall recurrence rate was 27.6 %. Group 1 had a significantly high (p < 0.05) recurrence rate of 50 %, while there was no difference in the recurrence rate between the last 3 schedules (Group 2:15 %; Group 3: 24.1 %; group 4: 27.2 %). Moreover, the recurrence rates of Ta or T1 tumors, and low-grade or high-grade tumors were not statistically different among these patient groups. Conclusion Our comparison of the different schedules of intravesical MMC instillation revealed a significantly higher recurrence rate with one MMC instillation post-TURBT than in patients with a maintenance dose of 8 weeks, 6 months, and 12 months. The time of the MMC maintenance schedule exhibited no significant differences between 8 weeks and 12 months. Thus, we conclude that for T1 or Ta high-risk NMIBC, MMC instillation can be performed once after TURBT, followed by a maintenance treatment once per week for 8 weeks.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Arsenos ◽  
K Gatzoulis ◽  
I Doundoulakis ◽  
P Dilaveris ◽  
C.K Antoniou ◽  
...  

Abstract Background Although some post myocardial infarction (post-MI) and dilated cardiomyopathy (DCM) patients with mid-range ejection fraction heart failure (HFmrEF = 40–49%) face an increased risk for arrhythmic Sudden Cardiac Death (SCD), current guidelines do not recommend an implantable cardioverter-defibrillator (ICD). Purpose To assess the accuracy of a novel multifactorial two-step approach, with noninvasive risk factors (NIRFs) leading to programmed ventricular stimulation (PVS), for SCD risk stratification of hospitalized HFmrEF patients. Methods Forty-eight patients (male=83%, age = 64±14 years, LVEF = 45±5%, ischemic coronary disease = 69%) underwent a NIRF presence screening first step with ECG, SAECG, echocardiography and 24 hour ambulatory ECG (Holter). Thirty-two patients with presence of one out of three NIRFs (SAECG ≥2 positive criteria for late potentials, ventricular premature beats ≥240/24 hours, and ≥1 episode of non-sustained ventricular tachycardia on Holter) were further stratified with PVS. Patients were classified as either low (Group 1, n=16, NIRFs−), moderate (Group 2, n=18, NIRFs+ /PVS−) or high risk (Group 3, n=14, NIRFs+/PVS+). All Group 3 patients received an ICD. Results After 41±18 months, 9 out of 48 patients experienced the major arrhythmic event (MAE) endpoint (clinical ventricular tachycardia/fibrillation = 3, appropriate ICD activation = 6). The endpoint occurred more frequently in Group 3 (7/14, 50%) than in Groups 1 & 2 (2/34, 5.8%). A logistic regression model adjusted for PVS, age and LVEF revealed that PVS was an independent MAE predictor (OR: 21.152, 95% CI: 2.618–170.887, p=0.004). Kaplan Meier curves diverged significantly (p logrank &lt;0.001) while PVS negative predictive value was 94%. Conclusion In hospitalized HFmrEF post-MI and DCM patients, a NIRFs leading to PVS two-step approach efficiently detected the subgroup at increased risk for MAEs. Funding Acknowledgement Type of funding source: None


2013 ◽  
Vol 95 (7) ◽  
pp. 523-528 ◽  
Author(s):  
C Rowlands ◽  
A Zyada ◽  
S Zouwail ◽  
H Joshi ◽  
MJ Stechman ◽  
...  

Introduction The effect of parathyroidectomy on the incidence of recurrent stone formation is uncertain. We aimed to compare the biochemistry and recurrence rate of urolithiasis in patients with primary hyperparathyroidism (pHPT) and stone formation (SF) and non-stone formation (NSF) with idiopathic stone formers (ISF). Methods Patients with pHPT and SF (Group 1) were identified from a prospective database. pHPT patients and NSF (Group 2) and ISFs (Group 3) were randomly selected from respective databases to form three equal groups. Preoperative and postoperative biochemical data were analysed and recurrent urolithiasis diagnosed if present on follow-up radiology. Out-of-area patients were asked about recurrence via telephone. Results From July 2002 to October 2011, 640 patients had parathyroidectomy for pHPT. Of these, 66 (10.3%) had a history of renal colic; one was lost to follow-up. Patient demographics were similar across all three groups. Three months post-parathyroidectomy, Groups 1 and 2 had significantly reduced serum calcium concentrations (p<0.01). Group 1 had lower urinary calcium excretion after parathyroidectomy (p<0.01), but estimated glomerular filtration rate did not change following surgery. During median follow-up of 4.33 years (0.25–9 years) in Groups 1 and 2 and 5.08 years (0.810–8 years) in Group 3, one patient (1.5%) in Group 1 and 16 patients (25%) in Group 3 had recurrent urolithiasis (p<0.01). No Group 2 patients developed stones. Conclusion Curative parathyroidectomy confers a low recurrence rate for urolithiasis, but does not prevent recurrence in all patients. Further research should aim to identify the risk factors for continued SF in these patients.


Author(s):  
P. Bagavandoss ◽  
JoAnne S. Richards ◽  
A. Rees Midgley

During follicular development in the mammalian ovary, several functional changes occur in the granulosa cells in response to steroid hormones and gonadotropins (1,2). In particular, marked changes in the content of membrane-associated receptors for the gonadotropins have been observed (1).We report here scanning electron microscope observations of morphological changes that occur on the granulosa cell surface in response to the administration of estradiol, human follicle stimulating hormone (hFSH), and human chorionic gonadotropin (hCG).Immature female rats that were hypophysectcmized on day 24 of age were treated in the following manner. Group 1: control groups were injected once a day with 0.1 ml phosphate buffered saline (PBS) for 3 days; group 2: estradiol (1.5 mg/0.2 ml propylene glycol) once a day for 3 days; group 3: estradiol for 3 days followed by 2 days of hFSH (1 μg/0.1 ml) twice daily, group 4: same as in group 3; group 5: same as in group 3 with a final injection of hCG (5 IU/0.1 ml) on the fifth day.


Sign in / Sign up

Export Citation Format

Share Document