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The clinical outcomes of isocitrate dehydrogenase‐wild‐type (IDH‐wt) lower‐grade glioma (LGG) have been the subject of debate for some time. In this meta‐analysis, we aimed to assess the prognostic values of several known genetic markers (e.g. TERT promoter mutation, H3F3A mutation, CDKN2A loss) in this tumor group. Four electronic databases, including PubMed, Scopus, Web of Science and Virtual Health Library, were searched for relevant articles. Pooled hazard ratio (HR) and corresponding 95% confidence interval (CI) for overall survival were calculated using a random‐effect model weighted by an inverse variance method. A total of 11 studies were finally selected from 2274 articles for meta‐analyses. Several genetic alterations were demonstrated to have a negative impact on prognosis of IDH‐wt LGGs, specifically TERT promoter mutation (HR, 1.96; 95% CI, 1.42–2.70), H3F3A mutation (HR, 3.21; 95% CI, 1.86–5.55) and EGFR amplification (HR, 1.67; 95% CI, 1.02–2.74). However, CDKN loss, ATRX mutation and coexisting gain of chromosome 7/loss of chromosome 10 showed no clinical significance in this glioma entity. Our study results demonstrated that IDH‐wt LGGs are heterogeneous in clinical outcome and not all tumors have a poor prognosis. The presence of TERT promoter mutation, H3F3A mutation and EGFR amplification showed negative prognostic impacts in this tumor entity. These genetic events can be used to better stratify patient outcomes. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses four cases of breast schistosomiasis japonica in Japan.

OBJECTIVE: To determine whether thymic stromal lymphopoietin (TSLP) plays a role in the resorption of herniated disc tissue. METHODS: The expression of TSLP messenger RNA (mRNA) and protein in mouse intervertebral disc cells was assessed by quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), and immunohistochemical analysis. The ability of mouse intervertebral disc cells to respond to TSLP stimulation was examined by Western blot analysis, ELISA, and protein array analysis. Intracellular signaling pathways involved in TSLP signaling in mouse intervertebral disc cells were investigated using several chemical inhibitors. The role of TSLP in macrophage migration into the intervertebral disc was assessed by in vitro migration assay. Finally, TSLP expression in clinical specimens derived from patients with a herniated disc was examined by immunohistochemistry. RESULTS: Mouse intervertebral disc cells expressed TSLP mRNA and protein upon stimulation with NF-kappaB-activating ligands such as tumor necrosis factor alpha. In addition, the mouse intervertebral disc cells expressed the TSLP receptor and produced monocyte chemotactic protein 1 (MCP-1; CCL2) and macrophage colony-stimulating factor in response to TSLP stimulation. Both anulus fibrosus and nucleus pulposus intervertebral disc cells expressed MCP-1 upon TSLP stimulation, which was mediated via the phosphatidylinositol 3-kinase/Akt pathway. Consistently, the supernatants of TSLP-activated intervertebral disc cultures had the capacity to induce macrophage migration in an MCP-1-dependent manner. Finally, TSLP and MCP-1 were coexpressed in human herniated disc specimens in which macrophage infiltration into the tissue was observed. CONCLUSION: TSLP induced by NF-kappaB-activating ligands in intervertebral discs may contribute to the recruitment of macrophages to the intervertebral disc by stimulating MCP-1 production and may be involved in the resorption of herniated disc tissue. [ABSTRACT FROM AUTHOR]

Aims: To clarify the clinicopathological significance of breast neuroendocrine ductal carcinoma in situ (NE-DCIS), i.e. DCIS in which >50% of cells immunohistochemically express NE markers (chromogranin A and/or synaptophysin), 20 NE-DCIS were studied and the findings compared with those of 274 non-NE-DCIS. Methods and results: NE-DCIS accounted for 6.8% of all DCIS. Mean patient age was 50.4 years for NE-DCIS and 49.6 years for non-NE-DCIS ( P = 0.66). The main clinical presentation of NE-DCIS was a bloody nipple discharge, seen in 72%, significantly different from the 5% in non-NE-DCIS cases ( P < 0.01). Carcinoma was preoperatively diagnosed in 67% of NE-DCIS and 95% of non-NE-DCIS cases ( P < 0.01). NE-DCIS was histologically characterized by a predominantly solid growth of cancer cells with fine-granular cytoplasm and ovoid, or occasionally spindle-shaped nuclei. A well-developed vascular network was also common. Nuclear grades and Van Nuys classification were significantly lower for NE-DCIS than for non-NE-DCIS ( P < 0.01). The mean MIB-1 labelling index was 4.3% in NE-DCIS and 8.1% in non-NE-DCIS ( P < 0.01). Furthermore, NE-DCIS cases had significantly higher oestrogen and progesterone receptor and lower HER2 scores than non-NE-DCIS cases ( P < 0.01). Conclusions: NE-DCIS has characteristic clinicopathological features and can, therefore, be regarded as a distinct variant of DCIS. [ABSTRACT FROM AUTHOR]

Background Transforming growth factor (TGF)-β plays an important role in the regulation of airway inflammation and remodelling in asthma. Recent studies suggest that TGF-β2 is a predominant isoform expressed in severe asthma and it is also associated with airway remodelling. Objective To determine whether the polymorphisms in TGF-β 2 are associated with childhood atopic bronchial asthma in a Japanese population. Methods We identified a total of eight polymorphisms and characterized the linkage disequilibrium (LD) mapping of the gene. Three variants in the promoter and 3′UTR were genotyped, and we conducted an association study of TGF-β 2 (childhood atopic asthma n=297, normal controls n=555). An association analysis of these variants and an expression and functional analysis were performed. Results 3′UTR 94862T >A was found to be significantly associated with the risk of childhood atopic asthma ( P=0.00041). The −109→ACAA ins promoter variant was also associated with the risk of childhood atopic asthma ( P=0.0037). TGF-β2 expression was observed in both the normal and asthmatic bronchial epithelium, and both real-time PCR and an ELISA showed a significant basal and TGF-β1-induced TGF-β2 expression in the bronchial epithelial cell line BEAS2B. Furthermore, the promoter variant −109→ACAA ins increased the TGF-β2 promoter-reporter activity in BEAS2B cells. Conclusions Our data suggest that TGF-β 2 may therefore be involved in the development of childhood atopic asthma by means of functional genetic polymorphism. The polymorphisms in TGF-β 2 may become important information for asthma susceptibility in children. [ABSTRACT FROM AUTHOR]

Aims: Gastric mucin expression has been demonstrated in a group of endocervical glandular lesions. The aim of this study was to gain further insight into endocervical lesions with a gastric phenotype. Methods and results: Various types of tunnel clusters (TC) were examined for gastric mucin by alcian blue/periodic acid–Schiff staining and immunohistochemistry for HIK1083. Five of 34 cases of TC expressed gastric mucin defined by PAS dominant neutral mucin and immunopositivity for pyloric gland mucin. Histologically, TC expressing gastric mucin showed lobular arrangements of small to medium-sized glands composed of mucin-rich columnar cells and were classified as Flumann's type A TC. Neither type B TC nor normal endocervical glands expressed PAS dominant neutral mucin and none of them was immunopositive for pyloric gland mucin. Five patients with type A TC of gastric phenotype ranged in age from 33 to 79 years (mean 58 years) and were multiparous. Type A TC of gastric phenotype, ranging from 2 to 4 mm in maximum diameter, were incidental findings in hysterectomy specimens. Conclusion: Type A TC of gastric phenotype could be related to lobular endocervical glandular hyperplasia of gastric phenotype. The pathogenesis of gastric metaplasia in TC remains unclear. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article about the elevation of CD73 and nucleotidase activity in papillary thyroid carcinomas.

T. Kawasaki, S. Nakamura, G. Sakamoto, T. Kondo, H. Tsunoda-Shimizu, Y. Ishii, T. Nakazawa, K. Mochizuki, T. Yamane, M. Inoue, S. Inoue and R. Katoh The purpose of this study was to clarify the cytological features of neuroendocrine ductal carcinoma in situ (NE-DCIS) of the breast. We analysed the cytopathological findings in 22 fine needle aspiration (FNA) smears and 17 nipple discharge smears obtained from 32 Japanese patients with NE-DCIS. The background of the FNA smears was clear (59%), mucoid (23%), haemorrhagic (14%) or necrotic (5%). Most of the FNA smears (95%) showed high cellularity. Characteristically, NE-DCIS cells were loosely arranged in three-dimensional solid clusters or singly dispersed. Well-developed vascular cores with or without malignant cells were occasionally recognized. The tumour cells were polygonal or spindle-shaped with a fine granular, abundant cytoplasm. Nuclei with finely granular chromatin were round or oval and often eccentrically located (plasmacytoid appearance). Mitotic figures were infrequent. Nuclear grade was estimated to be low in 86%. Most nipple discharge smears had fairly low cellularity with poorly preserved cell clusters in a markedly haemorrhagic background, although two (12%) were extremely cellular with cytological characteristics similar to those of the FNA smears. Pre-operative cytological malignant diagnoses were made in 42% of FNA smears and 0% of nipple discharge smears. Immunohistochemistry for neuroendocrine markers (chromogranin A and synaptophysin) confirmed the neuroendocrine nature of this tumour in adequate cytological specimens. NE-DCIS has distinctive cytological features and can therefore be diagnosed as a neuroendocrine tumour in most FNAs and some nipple discharge smears by cytological examination employing immunohistochemical techniques. We emphasize that a breast lesion with these features may be in situ and not invasive, and also that there is a risk of under-diagnosis. [ABSTRACT FROM AUTHOR]

To establish the mode of gene expression specified by transposon, we investigated the correlation among the homology of the DNA sequence, the extent of transposon-specific transcription, the specific activity of penicillinase (PCase) per cell, and the transposition frequency by using two ampicillin resistance transposons (TnAs), Tn2601 and Tn2602. Although both the TnAs specify the so-called type I PCase, Tn2602 always conferred 10- to 20-fold higher PCase activity per cell than Tn2601 regardless of the kind of replicon carrying TnA. The transposition freuency of Tn2602 also was 8 to 50 times higher than that of Tn2601 in all combinations of donor and recipients plasmids examined. As a result, the transposability expressed by the TnA was thought to correlate with the productivity of PCase in the cell specified by the corresponding TnA. The level of TnA-specific transcription of Tn2602 was noticeably higher than that of Tn2601, whereas the two TnAs shared a high degree (more than 90%) of DNA sequence homology. These results suggest that the difference in rates of transcription of the two transposons plays a key role in determining the difference in the productivity of PCase and the transposition-protein(s) of Tn2601 and Tn2602.