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The prognostic impact of TERT mutations has been controversial in IDH -wild tumors, particularly in glioblastomas (GBM). The controversy may be attributable to presence of potential confounding factors such as MGM T methylation status or patients’ treatment. This study aimed to evaluate the impact of TERT status on patient outcome in association with various factors in a large series of adult diffuse gliomas. We analyzed a total of 951 adult diffuse gliomas from two cohorts (Cohort 1, n  = 758; Cohort 2, n  = 193) for IDH1/2 , 1p/19q, and TERT promoter status. The combined IDH/TERT classification divided Cohort 1 into four molecular groups with distinct outcomes. The overall survival (OS) was the shortest in IDH wild-type/ TERT mutated groups, which mostly consisted of GBMs ( P  < 0.0001). To investigate the association between TERT mutations and MGMT methylation on survival of patients with GBM, samples from a combined cohort of 453 IDH -wild-type GBM cases treated with radiation and temozolomide were analyzed. A multivariate Cox regression model revealed that the interaction between TERT and MGMT was significant for OS ( P  = 0.0064). Compared with TERT mutant- MGMT unmethylated GBMs, the hazard ratio (HR) for OS incorporating the interaction was the lowest in the TERT mutant- MGMT methylated GBM (HR, 0.266), followed by the TERT wild-type- MGMT methylated (HR, 0.317) and the TERT wild-type- MGMT unmethylated GBMs (HR, 0.542). Thus, patients with TERT mutant- MGMT unmethylated GBM have the poorest prognosis. Our findings suggest that a combination of IDH , TERT , and MGMT refines the classification of grade II-IV diffuse gliomas.

Cluster of differentiation (CD) 166 or activated leukocyte cell adhesion molecule (ALCAM) is a transmembrane molecule known to be an intercellular adhesion factor. The expression and function of ALCAM in medulloblastoma (MB), a pediatric brain tumor with highly advanced molecular genetics, remains unclear. Therefore, this study aimed to clarify the significance and functional role of ALCAM expression in MB. ALCAM expression in 45 patients with MB was evaluated by immunohistochemical analysis of formalin-fixed paraffin-embedded clinical specimens and the relationship between ALCAM expression and pathological type/molecular subgroup, such as WNT, SHH, Group 3, and Group 4, was examined. Eight ALCAM positive (18%), seven partially positive (16%), and 30 negative (67%) cases were detected. All seven cases of the WNT molecular subgroup were ALCAM positive and ALCAM expression strongly correlated with this subgroup ( P < 0.0001). In addition, functional studies using MB cell lines revealed ALCAM expression affected proliferation and migration as a positive regulator in vitro . However, ALCAM silencing did not affect survival or the formation of leptomeningeal dissemination in an orthotopic mouse model, but did induce a malignant phenotype with increased tumor cell invasion at the dissemination sites (P = 0.0029). In conclusion, our results revealed that ALCAM exhibited highly specific expression in the WNT subgroup of MB. Furthermore, we demonstrated that the cell kinetics of MB cell lines can be altered by the expression of ALCAM.

•PRESTO grading can predict the growth potential of astrocytic tumors.•No spotty signal on PRESTO is associated with low-grade glioma.•PRESTO grading is associated with the proliferation ability of astrocytic tumors. Changes in brain tissue can be detected sensitively using PRESTO (principles of echo-shifting with a train of observations) magnetic resonance imaging (MRI). The aim of this study was to evaluate the correlation between the proliferative ability of astrocytoma and intratumoral spotty signal voids seen as hypo-intense dots on PRESTO MRI. Fifty-seven astrocytic tumors, comprising 14 astrocytomas, 12 anaplastic astrocytomas, and 31 glioblastomas, were included in this retrospective study. The tumors were classified independently by blinded radiologists according to the number of spotty signal voids detected on PRESTO-MRI as follows: spot-free (grade 0), less than 3 spots (grade 1), or more than 3 spots or a large spot (grade 2). Thirteen patients (92.9%) with astrocytoma were classified as PRESTO grade 0 and 1 patient (7.1%) was classified as grade 1. Seven patients (58.3%) with anaplastic astrocytoma were classified as PRESTO grade 0, 1 (8.3%) as grade 1, and 4 as grade 2 (33.3%). Three patients (9.7%) with glioblastoma were classified as grade 0, 6 (19.4%) as grade 1, and 22 (70.9%) as grade 2. There was a strong correlation between PRESTO tumor grade and the mean MIB-1 index. These results indicate that a grading system based on the number of spotty signal voids detected on PRESTO images would be useful for the diagnosis of astrocytic tumors and predicting their proliferative ability.

IntroductionThis study investigates the current state of clinical practice and molecular analysis for elderly patients with diffuse gliomas and aims to elucidate treatment outcomes and prognostic factors of patients with glioblastomas.MethodsWe collected elderly cases (≥ 70 years) diagnosed with primary diffuse gliomas and enrolled in Kansai Molecular Diagnosis Network for CNS Tumors. Clinical and pathological characteristics were analyzed retrospectively. Various factors were evaluated in univariate and multivariate models to examine their effects on overall survival.ResultsIncluded in the study were 140 elderly patients (WHO grade II: 7, III: 19, IV: 114), median age was 75 years. Sixty-seven patients (47.9%) had preoperative Karnofsky Performance Status score of ≥ 80. All patients underwent resection (gross-total: 20.0%, subtotal: 14.3%, partial: 39.3%, biopsy: 26.4%). Ninety-six of the patients (68.6%) received adjuvant treatment consisting of radiotherapy (RT) with temozolomide (TMZ). Seventy-eight of the patients (75.0%) received radiation dose of ≥ 50 Gy. MGMT promoter was methylated in 68 tumors (48.6%), IDH1/2 was wild-type in 129 tumors (92.1%), and TERT promoter was mutated in 78 of 128 tumors (60.9%). Median progression-free and overall survival of grade IV cases was 8.2 and 13.6 months, respectively. Higher age (≥ 80 years) and TERT promoter mutated were associated with shorter survival. Resection and adjuvant RT + TMZ were identified as independent factors for good prognosis.ConclusionsThis community-based study reveals characteristics and outcomes of elderly glioma patients in a real-world setting. Elderly patients have several potential factors for poor prognosis, but resection followed by RT + TMZ could lengthen duration of survival.

•DTI study of auditory pathway in patients with cerebellopontine angle tumors.•Analysis of FA values in the lateral lemniscus (LL) and the inferior colliculus (IC).•FA values in the both LL showed negative correlations with hearing impairment.•FA values in the ipsilateral IC showed negative correlations with hearing impairment. Recent reports demonstrated that acoustic nerve disorders affect the auditory pathway on diffusion tensor imaging (DTI). The aim was to investigate whether auditory pathway fractional anisotropy (FA) values are associated with audibility in patients with cerebellopontine angle tumors. Patients with cerebellopontine angle tumors were included in this retrospective study. Preoperatively, all patients underwent magnetic resonance imaging (MRI) including DTI. Two regions of interest on the lateral lemniscus (LL) and inferior colliculus (IC) were set bilaterally on DTI. FA values were calculated using software. Correlations between FA values and audibility were evaluated using Spearman’s rank correlation coefficient. Statistical significance was defined as p < 0.05. Seventeen patients with cerebellopontine angle tumors were included in this study. FA values in the bilateral LL showed a significant negative correlation with hearing impairment severity (r = −0.758, −0.600, p < 0.05). FA values on the ipsilateral side of the IC showed a significant negative correlation with hearing impairment severity (r = -0.477, p < 0.05). FA values on the contralateral side of the IC did not correlate with hearing impairment severity (r = -0.201, p > 0.05). One patient with a low FA value on the contralateral side of the IC had postoperative hearing impairment despite good preoperative hearing ability. FA values in the bilateral LL and on the ipsilateral side of the IC reflected hearing impairment severity. Decreased FA values on the contralateral side of the IC might predict hearing impairment postoperatively.