The structural, dielectric and piezoelectric properties of [Bi0.5(Na1-X K X )0.5]TiO3 ceramics were studied for the compositional range, X=0–1.0. The samples were prepared by a conventional sintering technique. From X-ray diffraction results, it was found that the morphotropic phase boundary (MPB) between (Bi0.5Na0.5)TiO3 (rhombohedral) and (Bi0.5K0.5)TiO3 (tetragonal) exists in the range of X=0.16–0.20. Polarization-Electric field hysteresis loops show that the remanent polarization at X=0.20 (BNTK20) is larger than that at X=0.0 (BNT). Peaks of electromechanical coupling factor, dielectric constant, piezoelectric constant and elastic compliance were obtained at X=0.16–0.20 of the MPB region. Dielectric and piezoelectric properties are enhanced in the MPB region for [Bi0.5(Na1-X K X )0.5]TiO3, similar to that observed for Pb(Zr, Ti)O3.

According to the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO), IDH-mutant astrocytic gliomas comprised WHO grade II diffuse astrocytoma, IDH-mutant (AII), WHO grade III anaplastic astrocytoma, IDH-mutant (AAIII), and WHO grade IV glioblastoma, IDH-mutant (GBM). Notably, IDH gene status has been made the major criterion for classification while the manner of grading has remained unchanged: it is based on histological criteria that arose from studies which antedated knowledge of the importance of IDH status in diffuse astrocytic tumor prognostic assessment. Several studies have now demonstrated that the anticipated differences in survival between the newly defined AII and AAIII have lost their significance. In contrast, GBM still exhibits a significantly worse outcome than its lower grade IDH-mutant counterparts. To address the problem of establishing prognostically significant grading for IDH-mutant astrocytic gliomas in the IDH era, we undertook a comprehensive study that included assessment of histological and genetic approaches to prognosis in these tumors. A discovery cohort of 211 IDH-mutant astrocytic gliomas with an extended observation was subjected to histological review, image analysis, and DNA methylation studies. Tumor group-specific methylation profiles and copy number variation (CNV) profiles were established for all gliomas. Algorithms for automated CNV analysis were developed. All tumors exhibiting 1p/19q codeletion were excluded from the series. We developed algorithms for grading, based on molecular, morphological and clinical data. Performance of these algorithms was compared with that of WHO grading. Three independent cohorts of 108, 154 and 224 IDH-mutant astrocytic gliomas were used to validate this approach. In the discovery cohort several molecular and clinical parameters were of prognostic relevance. Most relevant for overall survival (OS) was CDKN2A/B homozygous deletion. Other parameters with major influence were necrosis and the total number of CNV. Proliferation as assessed by mitotic count, which is a key parameter in 2016 CNS WHO grading, was of only minor influence. Employing the parameters most relevant for OS in our discovery set, we developed two models for grading these tumors. These models performed significantly better than WHO grading in both the discovery and the validation sets. Our novel algorithms for grading IDH-mutant astrocytic gliomas overcome the challenges caused by introduction of IDH status into the WHO classification of diffuse astrocytic tumors. We propose that these revised approaches be used for grading of these tumors and incorporated into future WHO criteria.

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Primary central nervous system lymphoma (PCNSL) is a rare malignancy confined to the central nervous system (CNS), and majority of PCNSL is pathologically classified as diffuse large B-cell lymphoma (DLBCL). We have now performed whole-exome sequencing for 41 tumor tissues of DLBCL-type PCNSL and paired normal specimens and also RNA-sequencing for 30 tumors, revealing a very high frequency of nonsynonymous somatic mutations in PIM1 (100 %), BTG2 (92.7 %), and MYD88 (85.4 %). Many genes in the NF-κB pathway are concurrently mutated within the same tumors. Further, focal deletion or somatic mutations in the HLA genes are associated with poor prognosis. Copy number amplification and overexpression of genes at chromosome 7q35 were both found to predict short progression-free survival as well. Oncogenic mutations in GRB2 were also detected, the effects of which in cultured cells were attenuated by inhibitors of the downstream kinases MAP2K1 and MAP2K2. Individuals with tumors positive for MYD88 mutations also harbored the same mutations at a low frequency in peripheral blood mononuclear cells, suggesting that MYD88 mutation-positive precancerous cells originate outside of the CNS and develop into lymphoma after additional genetic hits that confer adaptation to the CNS environment.

Purpose: Assessment of the proliferative ability of cancer cells is necessary not only for the biologic characterization of tumors, but also for the selection of treatment and evaluation of prognosis. Recently, there have been several studies examining the proliferative activity of various malignant tumors using immunohistochemical methods. PCNA is a nuclear protein related to the cell cycle and found with high expression in proliferative tissues, including cancers. Methods: In our study, to evaluate whether PCNA expression was useful as a prognostic factor in patients with pa-pillary thyroid carcinoma, we quantitated the immunohisto-chemical expression of PCNA in the formalin-fixed paraffin embedded tissue from 55 patients with papillary thyroid car-cinoma and correlated the results with established clinico-pathologic parameters. Results: The results were as follows. 1) PCNA expression in papillary thyroid carcinoma did not correlate with the age, sex or metastatic L/N activity of the patient, nor with the size, invasion, or recurrence of the tumor. 2) There was a close relationship between the expression rate of PCNA in thyroid tumor cells and that in metastatic L/N cells (p=0.056, in p0.1). 3) The expression of PCNA in the metastatic L/N (+) group was higher than in the metastatic L/N (-) group (p=0.045). Conclusion: It is suggested that PCNA expression is not an appropriate prognostic factor in papillary thyroid carcino-ma. (Korean J Endocrine Surg 2001;1:61-66)

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Olig2 is a recently identified transcription factor in-

BACKGROUND Intrahepatic disease recurrence is observed frequently after locoregional therapies for patients with hepatocellular carcinoma (HCC). However, the indication for locoregional therapy is still unclear. To clarify the indication for locoregional therapy for small HCC tumors, the authors measured the distance of microsatellites from the main tumor and analyzed the relation between this distance and clinicopathologic factors. METHODS The authors retrospectively analyzed 100 patients with small HCC tumors (≤ 5 cm in dimension) treated by curative hepatectomy. A microsatellite was defined as invasion into the portal vein or intrahepatic metastasis, and the distance from the main tumor to the most distant microsatellite was determined under light microscopy. The current study investigated the relation between microsatellite distance (0 mm if none present, ≤ 5 mm, and > 5 mm) and clinicopathologic factors, as well as overall and disease‐free survival rates after hepatectomy. RESULTS Of the 100 patients, 46 had microsatellites with a mean distance of 9.9 mm (median, 5.0 mm). Of the clinicopathologic factors investigated, tumor grade and preoperative α‐fetoprotein level significantly correlated with the presence of a microsatellite. Tumor size and distance to the microsatellite were significantly correlated. All but 1 tumor associated with a microsatellite distance > 5 mm was a high‐grade tumor > 25 mm in greatest dimension. The overall survival rate of patients with a microsatellite distance of > 5 mm was lower than that of patients with a microsatellite distance < 5 mm. CONCLUSIONS Locoregional therapy, including limited resection and ablation therapies, was appropriate for patients with low‐grade HCC tumors or with tumors < 25 mm in diameter. Cancer 2005. © 2004 American Cancer Society.