The Epigenetic Regulator Jumonji Domain-Containing Protein 6 (JMJD6) Is Highly Expressed but Not Prognostic in IDH-Wildtype Glioblastoma Patients

2021 ◽  
Author(s):  
Ann Mari Rosager ◽  
Rikke H Dahlrot ◽  
Mia D Sørensen ◽  
Julie A Bangsø ◽  
Steinbjørn Hansen ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Performance Status ◽  
Gender Performance ◽  
Who Grade ◽  
Epigenetic Regulator ◽  
Long Time ◽  
Grade Ii ◽  
Astrocytic Gliomas ◽  
Support Treatment ◽  
Mgmt Promoter Status

Abstract Patients with IDH-wildtype glioblastoma (GBM) generally have a poor prognosis. However, there is an increasing need of novel robust biomarkers in the daily clinico-pathological setting to identify and support treatment in patients who become long-time survivors. Jumonji domain-containing protein 6 (JMJD6) is involved in epigenetic regulation of demethylation of histones and has been associated with GBM aggressiveness. We investigated the expression and prognostic potential of JMJD6 tumor fraction score in 184 IDH-wildtype GBMs. Whole-slides were double-stained with an antibody against JMJD6 and an exclusion-cocktail consisting of 4 antibodies (CD31, SMA, CD45, and Iba-1), enabling evaluation of tumor cells only. Stainings were quantified with a combined software- and scoring-based approach. For comparison, IDH-mutated WHO grade II, III and IV astrocytic gliomas were also stained, and the JMJD6 tumor fraction score increased with increasing WHO grade, although not significantly. In multivariate analysis including age, gender, performance status and post-surgical treatment high JMJD6 tumor fraction score was associated with longer overall survival in IDH-wildtype GBMs (p = 0.03), but the effect disappeared when MGMT promoter status was included (p = 0.34). We conclude that JMJD6 is highly expressed in IDH-wildtype GBM but it has no independent prognostic value.

Clinical, histopathological, and molecular analyses of IDH-wild-type WHO grade II–III gliomas to establish genetic predictors of poor prognosis

2019 ◽  
Vol 36 (4) ◽  
pp. 135-143 ◽  
Author(s):  
Kiyonori Kuwahara ◽  
Shigeo Ohba ◽  
Shunsuke Nakae ◽  
Natsuki Hattori ◽  
Eriel Sandika Pareira ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Wild Type ◽  
Who Grade ◽  
Molecular Analyses ◽  
Genetic Predictors ◽  
Grade Ii

scholarly journals Objective Response to Radiation Therapy and Long-Term Survival of Patients with WHO Grade II Astrocytic Gliomas with Known LOH 1p/19q Status

2007 ◽  
Vol 183 (9) ◽  
pp. 517-522 ◽  
Author(s):  
Ali-Reza Fathi ◽  
Erik Vassella ◽  
Marlene Arnold ◽  
Jürgen Curschmann ◽  
Michael Reinert ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Objective Response ◽  
Who Grade ◽  
Term Survival ◽  
Long Term Survival ◽  
Grade Ii ◽  
Astrocytic Gliomas

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.

Docetaxel, 5-fluorouracil and nedaplatin as second-line chemotherapy for patients with esophageal cancer after esophagectomy: A pilot study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14140-14140 ◽  
Author(s):  
K. Mafune ◽  
K. Yamada ◽  
K. Imamura ◽  
K. Kubota ◽  
M. Kaminishi
Keyword(s):  
Esophageal Cancer ◽  
Pilot Study ◽  
Cell Carcinoma ◽  
Performance Status ◽  
Second Line ◽  
Ecog Performance Status ◽  
Who Grade ◽  
Second Line Chemotherapy ◽  
Grade Ii ◽  
Line Chemotherapy

14140 Background: We investigated the combination of docetaxel, 5-fluorouracil (5FU) and cisplatin analog, nedaplatin (CDGP) as second-line chemotherapy after esophagectomy. Methods: Eight patients with recurrent esophageal cancer who had undergone adjuvant 5FU/cisplatin after esophagectomy were included this study (7 male, 1 female; median ECOG performance status: 1). Histologic type of all esophageal cancer was squamous cell carcinoma. Patients received docetaxel 60 mg/m2 on day 1, 5FU 600 mg/m2 on days 1–5, and CDGP60 mg/m2 on day 4 every 3 weeks. A total of 17 chemotherapy cycles was administered. The median number of cycles was 2 (range 1–5). Results: The overall response rate was 62.5%. The median overall survival was 42 weeks, and the median progression-free survival was 26 weeks. Hematological and non-hematological toxicities were moderate (neutropenia WHO grade III/IV: 62.5%, alopecia grade II/III: 75%, nausea/vomiting grade II/III: 50%, neurotoxicity grade II: 12.5%). Conclusions: The combination of docetaxel, 5FU and CDGP is an active regimen with moderate toxicity in the treatment of patients with recurrent esophageal cancer. This pilot study suggests the feasibility of a combination treatment containing a taxan, 5FU and cisplatin or its analog in esophageal squmaous cell carcinoma. No significant financial relationships to disclose.

scholarly journals 5-hydroxymethylcytosine loss is associated with poor prognosis for patients with WHO grade II diffuse astrocytomas

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Feng Zhang ◽  
Yifan Liu ◽  
Zhiwen Zhang ◽  
Jie Li ◽  
Yi Wan ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Who Grade ◽  
Grade Ii

scholarly journals NCOG-41. FUNCTIONAL OUTCOME FOLLOWING NON-DOMINANT HEMISPHERIC GLIOMA SURGERY FROM THE ASPECT OF INDEPENDENCE LEVEL, COGNITIVE FUNCTION AND RETURN TO SOCIAL LIVES

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii138-ii138
Author(s):  
Riho Nakajima ◽  
Masashi Kinoshita ◽  
Hirokazu Okita ◽  
Mitsutoshi Nakada
Keyword(s):  
Cognitive Function ◽  
Functional Outcome ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Chronic Phase ◽  
University Hospital ◽  
Glioma Surgery ◽  
Who Grade ◽  
Social Lives ◽  
Grade Ii

Abstract BACKGROUND Functional outcome has been paid much attention in surgery for eloquent area or dominant hemisphere. Little is known about functional outcome following surgery for non-dominant hemispheric gliomas, although some resent reports revealed the importance of right cerebral hemisphere on glioma surgery. Here, we investigated functional outcome of right cerebral hemispheric gliomas from the aspect of independence level, cognitive function, and return to social lives. METHODS Totally 82 patients with right cerebral hemispheric gliomas who underwent surgery for resection in Kanazawa university hospital were studied. Patients were divided into two groups, WHO grade II/III and IV. Karnofsky Performance Status (KPS), Mini-mental state examination (MMSE), and whether or not to return to work at pre-operation and chronic phase were evaluated. To reveal responsible region for decline of each index, the voxel-based lesion symptom (VLSM) analyses were performed. RESULTS MMSE; no difference was found through postoperative course in grade II/III, whereas postoperative score of grade IV was declined significantly compared with pre-operation (25.1 and 21.9 point; p=0.048). KPS; preoperative independence level was maintained until chronic phase in grade II/III (94.7 and 89.5). While, in grade IV, postoperative KPS was declined significantly than that of pre-operation (82.0 and 70.0, p=0.007). Results of the VLSM analysis revealed that patients who resected temporo-parietal junction in grade IV showed significantly low KPS score. Return to social lives; Reintegration ratio of working population was 71% and 35% for grade II/III and IV, respectively. Of these, as for grade II/III gliomas, the cingulate cortex and medial orbito-frontal cortex relate to return to social lives. CONCLUSIONS Functional outcome following surgery depends on tumor grade and resected region in right cerebral hemispheric gliomas.

scholarly journals ACTR-14. A PROSPECTIVE RANDOMIZED STUDY OF CONCURRENT CHEMORADIOTHERAPY WITH TEMOZOLOMIDE VERSUS RADIOTHERAPY ALONE IN PATIENTS WITH IDH WILD-TYPE/TERT PROMOTER MUTATION GRADE II/III GLIOMAS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi15-vi15
Author(s):  
Yanwei Liu ◽  
Xia Shan ◽  
Xiaoguang Qiu
Keyword(s):  
Concurrent Chemoradiotherapy ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Univariate Analysis ◽  
Promoter Mutation ◽  
Who Grade ◽  
Adjuvant Temozolomide ◽  
Dismal Prognosis ◽  
Significant Difference ◽  
Grade Ii

Abstract Our previous data showed that WHO grade II/III gliomas with isocitrate dehydrogenase wide-type (IDH-wt) and telomerase reverse transcriptase promoter mutation (TERTp-mut) have dismal prognosis as glioblastoma. This study compared concurrent chemoradiotherapy(CRT) with radiotherapy(RT) alone on the outcome of these patients. Between September 2016 and November 2018, 30 eligible grade II/III glioma patients with IDH-wt and TERTp-mut were randomly assigned to receive either RT (60 Gy in 30 daily fractions for 6 weeks) alone (n=15) or concurrent CRT with daily temozolomide and adjuvant temozolomide (n=15). The median follow-up duration was 15.5 months. The median age was 51 years (range, 24–66 years). The median Karnofsky performance status (KPS) score at randomization was 80 (range, 60–80). Surgery was the primary treatment. The characteristics of the two treatment groups were well balanced at baseline. The 1-year OS rate was significant difference between CRT group (92.3%; 95% CI: 77.8–100) and RT alone group(71.1%; 95% CI: 47.0–95.2) (p = 0.019). Local, distant, and combined tumor recurrence patterns were observed in 4 (26.7%), 1 (6.7%), and 3 patients (20%) in the CRT group and 4 (26.7%), 3 (20%), and 3 patients (20%) in the RT alone group. Those treated with RT alone had shorter median PFS (9 vs 18 months, HR: 0.517; 95% CI: 0.193 to 1.386; p = 0.19). CRT with temozolomide and extent of resection were statistically significant predictors for survival on univariate analysis. Multivariate analysis showed that CRT was associated with a significantly better OS compared with RT alone (OR=0.195; 95% CI, 0.044 to 0.867; p=0.032). Consequently, concurrent CRT with daily temozolomide and adjuvant temozolomide for newly diagnosed IDHwt/TERTp-mut grade II/III gliomas had significantly better OS compared with RT alone. A large multi-center prospective randomized trial is warranted. The trial has been registered at ClinicalTrials.gov (NCT02766270).

scholarly journals Influence of VEGF-A, VEGFR-1-3, and neuropilin 1-2 on progression-free: and overall survival in WHO grade II and III meningioma patients

2021 ◽  
Vol 52 (2) ◽  
pp. 233-243
Author(s):  
Simon Bernatz ◽  
Daniel Monden ◽  
Florian Gessler ◽  
Tijana Radic ◽  
Elke Hattingen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Cells ◽  
Progression Free Survival ◽  
Staining Intensity ◽  
Who Grade ◽  
Positive Correlation ◽  
Protein Levels ◽  
Angiogenic Therapy ◽  
Neuropilin 1 ◽  
Grade Ii

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.

scholarly journals Predictors of Survival in Subtotally Resected WHO Grade I Skull Base Meningiomas

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1451
Author(s):  
Michele Da Broi ◽  
Paola Borrelli ◽  
Torstein R. Meling
Keyword(s):  
Skull Base ◽  
Clinical Outcomes ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Advanced Age ◽  
Final Visit ◽  
Subtotal Resection ◽  
Who Grade ◽  
Skull Base Meningiomas

Background: Although gross total resection (GTR) is the goal in meningioma surgery, this can sometimes be difficult to achieve in skull base meningiomas. We analyzed clinical outcomes and predictors of survival for subtotally resected benign meningiomas. Methods: A total of 212 consecutive patients who underwent subtotal resection (STR) for benign skull base meningioma between 1990–2010 were investigated. Results: Median age was 57.7 [IQR 18.8] years, median preoperative Karnofsky performance status (KPS) was 80.0 [IQR 20.0], 75 patients (35.4%) had posterior fossa meningioma. After a median follow-up of 6.2 [IQR 7.9] years, retreatment (either radiotherapy or repeated surgery) rate was 16% at 1-year, 27% at 3-years, 34% at 5-years, and 38% at 10-years. Ten patients (4.7%) died perioperatively, 9 (3.5%) had postoperative hematomas, and 2 (0.8%) had postoperative infections. Neurological outcome at final visit was improved/stable in 122 patients (70%). Multivariable analysis identified advanced age and preoperative KPS < 70 as negative predictors for overall survival (OS). Patients who underwent retreatment had no significant reduction of OS. Conclusions: Advanced age and preoperative KPS were independent predictors of OS. Retreatments did not prolong nor shorten the OS. Clinical outcomes in STR skull base meningiomas were generally worse compared to cohorts with high rates of GTR.

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