Aims: Columnar cell lesions (CCLs) are recognised breast cancer precursor lesions. Intraductal papillomas are usually lined by benign (polyclonal) cells. Although papillomas with monoclonal lesions (atypical ductal hyperplasia (ADH)/ductal carcinoma in situ (DCIS)) have been described, CCLs have not been described in papillomas.
Methods: We present two papillary breast lesions lined by a single layer of luminal cells resembling atypical CCL/flat epithelial atypia (FEA). We compared these two lesions with 13 benign intraductal papillomas, and 2 papillomas with ADH/DCIS grade 1 features as controls were immunohistochemically stained for the oestrogen receptor alpha (oestrogen receptor) and progesterone receptors (PR), cytokeratin 5 (CK5) and cyclin D1.
Results: Oestrogen receptor/PR expression was variable, with areas with ≥85% hormone receptor positivity in both morphologically normal papillomas and papillomas with ADH. In ADH areas, CK5 expression was seen in ≤5% of cells while cyclin D1 expression was high (>60%). The two papillary lesions with FEA were 100% oestrogen receptor and 90% cyclin D1 positive, and low on PR/CK5. There was only one morphologically normal papilloma with similar areas of low CK5 (5%) and high cyclin D1 expression; in all other morphologically benign papillomas CK5 expression varied between 10% and 50% and cyclin D1 expression was ≤50%. The papillary lesion with FEA that could be tested showed 16q losses, the hallmark genetic change in low nuclear grade breast neoplasias, in contrast to nine morphologically benign papillomas that could be tested.
Conclusion: We present two papillomatous breast lesions with atypical CCL morphology and 16q loss, for which we propose the term papillary FEA.
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http://dx.doi.org/10.1136/jcp-2022-208389 | DOI Listing |
Nat Protoc
January 2025
Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Premetastatic cancer cells often spread from the primary lesion through the lymphatic vasculature and, clinically, the presence or absence of lymph node metastases impacts treatment decisions. However, little is known about cancer progression via the lymphatic system or of the effect that the lymphatic environment has on cancer progression. This is due, in part, to the technical challenge of studying lymphatic vessels and collecting lymph fluid.
View Article and Find Full Text PDFNature
January 2025
Stanford Cancer Institute, School of Medicine, Stanford University, Stanford, CA, USA.
Breast cancer is a highly heterogeneous disease whose prognosis and treatment as defined by the expression of three receptors-oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 (HER2; encoded by ERBB2)-is insufficient to capture the full spectrum of clinical outcomes and therapeutic vulnerabilities. Previously, we demonstrated that transcriptional and genomic profiles define eleven integrative subtypes with distinct clinical outcomes, including four ER subtypes with increased risk of relapse decades after diagnosis. Here, to determine whether these subtypes reflect distinct evolutionary histories, interactions with the immune system and pathway dependencies, we established a meta-cohort of 1,828 breast tumours spanning pre-invasive, primary invasive and metastatic disease with whole-genome and transcriptome sequencing.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Radiology, The Second Affiliated Hospital of Wannan Medical College, Kangfu Road, Wuhu, 241006, China.
This study aimed to develop a Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression (LR) model using quantitative imaging features from Shear Wave Elastography (SWE) and Contrast-Enhanced Ultrasound (CEUS) to assess the malignancy risk of BI-RADS 4 breast lesions (BLs). The features predictive of malignancy in the LASSO analysis were used to construct a nomogram. Female patients (n = 111) with BI-RADS 4 BLs detected via routine ultrasound at Ma'anshan People's Hospital underwent SWE, CEUS, and histopathological examinations were enrolled in this study.
View Article and Find Full Text PDFClin Oncol (R Coll Radiol)
December 2024
Netherlands Comprehensive Cancer Organisation (IKNL), Department of Research and Development, Godebaldkwartier 419, 3511 DT Utrecht, the Netherlands; University of Twente, Department of Health Technology and Services Research, Technical Medical Center, Hallenweg 5, 7522 NH Enschede, the Netherlands.
Aims: Ductal Carcinoma In Situ (DCIS) treated by breast-conserving surgery followed by radiotherapy aims to decrease the probability of locally recurrent disease. The role of whole breast irradiation, specifically in DCIS having low recurrence risk and low risk of becoming invasive, is increasingly debated. Also, the added value of applying boost irradiation in DCIS has been questioned.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland.
Copper compounds with artificial metallo-nuclease (AMN) activity are mechanistically unique compared to established metallodrugs. Here, we describe the development of a new dinuclear copper AMN, Cu2-BPL-C6 (BPL-C6 = bis-1,10-phenanthroline-carbon-6), prepared using click chemistry that demonstrates site-specific DNA recognition with low micromolar cleavage activity. The BPL-C6 ligand was designed to force two redox-active copper centres-central for enhancing AMN activity-to bind DNA, via two phenanthroline ligands separated by an aliphatic linker.
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