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Context.--The updated American Society of Clinical Oncology/College of American Pathologists guideline for human epidermal growth factor receptor 2 (HER2) testing in breast cancer requires pathologists to re-evaluate HER2 status. Objective.--To define HER2 status of breast cancer using immunohistochemistry and fluorescence in situ hybridization. Design.--Diagnostic reports of invasive breast cancers made between 2014 and 2018 with HER2 immunohistochemistry and fluorescence in situ hybridization results were retrieved. HER2 status was re-defined using the updated recommendations. Results.--Of 2514 tumors, 89.7% (2254 of 2514) suggested for fluorescence in situ hybridization assay were HER2 immunohistochemistry 2+. Approximately 8.9% (225 of 2514) and 1.4% (35 of 2514) of tumors were of immunohistochemistry 0/1+ and 3+, respectively. Based on the average HER2 copy number and HER2:CEP17 ratio, tumors were assigned into 5 groups, including 13.1% (330 of 2514) group 1 tumors, 2.1% (52 of 2514) group 2 tumors, 1.1% (27 of 2514) group 3 tumors, 7.0% (175 of 2514) group 4 tumors, and 76.8% (1930 of 2514) group 5 tumors. In combination with immunohistochemistry, all tumors in group 2 and group 4 changed HER2 status, from positive and equivocal into negative, respectively, while group 3 tumors remained positive. Comparative analyses of clinicopathologic features of tumors in different groups revealed that group 2 and 4 tumors displayed worse clinicopathologic features than those of group 5, while group 3 tumors shared similar clinicopathologic features to those of group 1. Conclusions.--Following the updated guideline, HER2 status is clearly designated. Significant differences regarding clinical features were observed between tumors in different groups but they share the same HER2 status, suggesting further validation of the accuracy of this diagnostic approach is warranted. (Arch Pathol Lab Med. 2020;144:1097-1107; doi: 10.5858/arpa.2019-0369-OA), Human epidermal growth factor receptor 2 (HER2) status can be revealed by HER2 gene status tested by in situ hybridization (ISH) assay or HER2 protein expression assessed by immunohistochemistry (IHC). [...]

The immune response is highly active in Alzheimer's disease (AD). Identification of genetic risk contributed by immune genes to AD may provide essential insight for the prognosis, diagnosis, and treatment of this neurodegenerative disease. In this study, we performed a genetic screening for AD-related top immune genes identified in Europeans in a Chinese cohort, followed by a multiple-stage study focusing on Complement Factor H (CFH) gene. Effects of the risk SNPs on AD-related neuroimaging endophenotypes were evaluated through magnetic resonance imaging scan, and the effects on AD cerebrospinal fluid biomarkers (CSF) and CFH expression changes were measured in aged and AD brain tissues and AD cellular models. Our results showed that the AD-associated top immune genes reported in Europeans (CR1, CD33, CLU, and TREML2) have weak effects in Chinese, whereas CFH showed strong effects. In particular, rs1061170 (P(meta)=5.0 × 10(-4)) and rs800292 (P(meta)=1.3 × 10(-5)) showed robust associations with AD, which were confirmed in multiple world-wide sample sets (4317 cases and 16 795 controls). Rs1061170 (P=2.5 × 10(-3)) and rs800292 (P=4.7 × 10(-4)) risk-allele carriers have an increased entorhinal thickness in their young age and a higher atrophy rate as the disease progresses. Rs800292 risk-allele carriers have higher CSF tau and Aβ levels and severe cognitive decline. CFH expression level, which was affected by the risk-alleles, was increased in AD brains and cellular models. These comprehensive analyses suggested that CFH is an important immune factor in AD and affects multiple pathological changes in early life and during disease progress.

Non-small cell lung cancer (NSCLC) is one of the causes of cancer mortality worldwide. The role of miR-26 in the development and progression of NSCLC remains largely unknown. In this study we found an abnormal expression of miR-26 in human NSCLC tissues. It was found that miR-26 mimics induced cell apoptosis and promoted caspase-3, 9 activities in human NSCLC cells. The miR-26 inhibitor enhanced the expression of the light chain 3 (LC3) protein and the autophagy related genes in NSCLC cells. Moreover, miR-26 regulated apoptosis and autophagy by inhibiting TGF-β expression in a JNK dependent manner. In addition, miR-26 mimics induced cell apoptosis, was involved in the endoplasmic reticulum stress (ERS) signaling pathway. Down-regulation of the ERS, inhibited apoptosis which was induced by miR-26 mimics in NSCLC cells. In in vivo studies, TUNEL staining revealed that the number of TUNEL positive cells of the tumor tissue in the miR-26 treatment group, were significantly increased in comparison with the control group, while the number of TUNEL positive cells in the tumor tissue were remarkably decreased in the groups treated with miR-26, combined with the TGF-β1 inhibitor or JNK inhibitor. Additionally, the immunoreactivity of TGF-β1 in the cells treated with the miR-26 inhibitor, decreased in comparison to the control group. Our results indicated that miR-26 induced apoptosis and inhibited autophagy in human NSCLC cells through the TGF-β1-JNK signaling pathway, suggesting that miR-26 could be a potential novel target for the treatment of NSCLC.

Wavelet transformation has been widely used in geophysical and geochemical exploration, and the fractal feature of wavelet coefficients has recently stood out from many wavelet threshold methods. We introduced the wavelet–fractal method to analyze the polarizability and resistivity of graphite deposits. Due to the unique nature of graphite-bearing gneiss, characterized by high polarizability and low resistivity, we concluded that the polarizability background mode is better suited to depict the morphology of the graphite-bearing formation, with the resistivity background mode serving as complementary information for verification. Symlets5 is regarded as the optimal mother wavelet to indicate the characteristics of graphite ore by means of comparison and analysis. The polarizability anomalies showed two different linear forms: the direction of the measuring line and the strike of the ore bodies. According to the data of drill holes on the profile, we inferred that the high values of the anomaly mode can be used to delineate the target area where the graphite is enriched. Combining the application of both modes, we used the wavelet–fractal method for the quantitative prediction and effective selection of a potential area with a high grade. The approach used in this current study can be extended to the prospecting of other graphite deposits or sedimentary–metamorphic deposits containing conductive minerals, where geochemical and geophysical data are available. [ABSTRACT FROM AUTHOR]