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Item Meta-Analysis: Contrast-Enhanced Ultrasound Versus Conventional Ultrasound for Differentiation of Benign and Malignant Breast Lesions(Elsevier, 2018-05) Li, Qian; Hu, Min; Chen, Zhikui; Li, Changtian; Zhang, Xi; Song, Yiqing; Xiang, Feixiang; Epidemiology, School of Public HealthThis meta-analysis aimed to compare the diagnostic performance of contrast-enhanced ultrasound (CEUS), conventional ultrasound (US) combined with CEUS (US + CEUS) and US for distinguishing breast lesions. From thorough literature research, studies that compared the diagnostic performance of CEUS versus US or US + CEUS versus US, using pathology results as the gold standard, were included. A total of 10 studies were included, of which 9 compared the diagnostic performance of CEUS and US, and 5 studies compared US + CEUS and US. In those comparing CEUS versus US, the pooled sensitivity was 0.93 (95% CI: 0.91–0.95) versus 0.87 (95% CI: 0.85–0.90) and pooled specificity was 0.86 (95% CI: 0.84–0.88) versus 0.72 (95% CI: 0.69–0.75). In studies comparing US + CEUS versus US, the pooled sensitivity was 0.94 (95% CI: 0.92–0.96) versus 0.87 (95% CI: 0.84–0.90) and pooled specificity was 0.86 (95% CI: 0.82–0.89) versus 0.80 (95% CI: 0.76–0.84). In terms of diagnosing breast malignancy, areas under the curve of the summary receiver operating characteristic (of both CEUS (p = 0.003) and US + CEUS (p = 0.000) were statistically higher than that of US. Both CEUS alone and US + CEUS had better diagnostic performance than US in differentiation of breast lesions, and US + CEUS also had low negative likelihood ratio.Item MYBL1 rearrangements and MYB amplification in breast adenoid cystic carcinomas lacking the MYB–NFIB fusion gene(Wiley, 2017) Kim, Jisun; Geyer, Felipe C.; Martelotto, Luciano G.; Ng, Charlotte K. Y.; Lim, Raymond S.; Selenica, Pier; Li, Anqi; Pareja, Fresia; Fusco, Nicola; Edelweiss, Marcia; Kumar, Rahul; Gularte-Merida, Rodrigo; Forbes, Andre N.; Khurana, Ekta; Mariani, Odette; Badve, Sunil; Vincent-Salomon, Anne; Norton, Larry; Reis-Filho, Jorge S.; Weigelt, Britta; Pathology and Laboratory Medicine, School of MedicineBreast adenoid cystic carcinoma (AdCC), a rare type of triple-negative breast cancer, has been shown to be driven by MYB pathway activation, most often underpinned by the MYB–NFIB fusion gene. Alternative genetic mechanisms, such as MYBL1 rearrangements, have been reported in MYB–NFIB-negative salivary gland AdCCs. Here we report on the molecular characterization by massively parallel sequencing of four breast AdCCs lacking the MYB–NFIB fusion gene. In two cases, we identified MYBL1 rearrangements (MYBL1–ACTN1 and MYBL1–NFIB), which were associated with MYBL1 overexpression. A third AdCC harboured a high-level MYB amplification, which resulted in MYB overexpression at the mRNA and protein levels. RNA-sequencing and whole-genome sequencing revealed no definite alternative driver in the fourth AdCC studied, despite high levels of MYB expression and the activation of pathways similar to those activated in MYB–NFIB-positive AdCCs. In this case, a deletion encompassing the last intron and part of exon 15 of MYB, including the binding site of ERG-1, a transcription factor that may downregulate MYB, and the exon 15 splice site, was detected. In conclusion, we demonstrate that MYBL1 rearrangements and MYB amplification probably constitute alternative genetic drivers of breast AdCCs, functioning through MYBL1 or MYB overexpression. These observations emphasize that breast AdCCs probably constitute a convergent phenotype, whereby activation of MYB and MYBL1 and their downstream targets can be driven by the MYB–NFIB fusion gene, MYBL1 rearrangements, MYB amplification, or other yet to be identified mechanisms. Copyright © 2017 Pathological Society of Great Britain and Ireland.Item Phenotypic plasticity in normal breast derived epithelial cells(Biomed Central, 2014) Sauder, Candice A. M.; Koziel, Jillian E.; Choi, MiRan; Fox, Melanie J.; Grimes, Brenda R.; Badve, Sunil S.; Blosser, Rachel J.; Radovich, Milan; Lam, Christina C.; Vaughan, Melville B.; Herbert, Brittney-Shea; Clare, Susan E.; Pathology and Laboratory Medicine, School of MedicineBackground Normal, healthy human breast tissue from a variety of volunteer donors has become available for research thanks to the establishment of the Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center (KTB). Multiple epithelial (K-HME) and stromal cells (K-HMS) were established from the donated tissue. Explant culture was utilized to isolate the cells from pieces of breast tissue. Selective media and trypsinization were employed to select either epithelial cells or stromal cells. The primary, non-transformed epithelial cells, the focus of this study, were characterized by immunohistochemistry, flow cytometry, and in vitro cell culture. Results All of the primary, non-transformed epithelial cells tested have the ability to differentiate in vitro into a variety of cell types when plated in or on biologic matrices. Cells identified include stratified squamous epithelial, osteoclasts, chondrocytes, adipocytes, neural progenitors/neurons, immature muscle and melanocytes. The cells also express markers of embryonic stem cells. Conclusions The cell culture conditions employed select an epithelial cell that is pluri/multipotent. The plasticity of the epithelial cells developed mimics that seen in metaplastic carcinoma of the breast (MCB), a subtype of triple negative breast cancer; and may provide clues to the origin of this particularly aggressive type of breast cancer. The KTB is a unique biorepository, and the normal breast epithelial cells isolated from donated tissue have significant potential as new research tools.