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Purpose Breast hamartomas are rarely associated with epithelial atypia or malignancy. Since the introduction of digital mammography in the UK from 2008, hamartoma detection has increased. The aim of this study was to identify if there are characteristic clinical, radiological or histological features that distinguish hamartomas with intralesional atypia/malignancy (complex hamartomas, CH) or ipsilateral/contralateral atypia/malignancy (non-CH) from those without atypia/malignancy at diagnosis (other benign hamartomas, BH). Methods We performed a retrospective single-institution review of 450 hamartomas reported between 2010 and 2023. Anonymised H&E sections and imaging of CH and non-CH were reviewed to identify distinguishing features. Results 13,441 benign breast lesions were biopsied/resected between 2010 and 2023 including 450 hamartomas (3.3%), 19 of which (4.2%) were associated with atypia or malignancy. 14 were analysed further (7 CH; 7 non-CH). The mean age of CH plus non-CH patients was significantly higher than patients with BH (47.5 vs. 40.6 years; p  = 0.03). The mean size of CH was greater than non-CH (32.1 mm vs.17.6 mm; p  = 0.06). There was a statistically significantly higher incidence of atypical/malignant lobular lesions (ALH/LCIS/ILC) in CH vs. non-CH (42.9% vs 0%; p  = 0.05). MRI was performed in 2 CH and 3 non-CH; in all 5 the associated malignancy was detected. There was no significant difference between the CH and non-CH group in ultrasound/mammographic features, other hamartoma histological features or other associated benign breast changes. Conclusions Ultrasound/mammogram are not sufficiently sensitive to identify hamartomas with associated atypia/malignancy. Certain hamartoma features may preferentially be associated with atypia/malignancy and which merit further radiological and/or detailed histological investigation.

MicroRNAs are a class of small RNAs that are increasingly being recognized as important regulators of gene expression. Although hundreds of microRNAs are present in the mammalian genome, genetic studies addressing their physiological roles are at an early stage. We have shown that mice deficient for bic/microRNA-155 are immunodeficient and display increased lung airway remodeling. We demonstrate a requirement of bic/microRNA-155 for the function of B and T lymphocytes and dendritic cells. Transcriptome analysis of bic/microRNA-155-deficient CD4⁺ T cells identified a wide spectrum of microRNA-155-regulated genes, including cytokines, chemokines, and transcription factors. Our work suggests that bic/microRNA-155 plays a key role in the homeostasis and function of the immune system.

Intravenous administration of a fluorescently labeled c-Met–binding peptide enables visualization of polyps not detected using white light. Colon cancer prevention currently relies on colonoscopy using white light to detect and remove polyps, but small and flat polyps are difficult to detect and frequently missed when using this technique. Fluorescence colonoscopy combined with a fluorescent probe specific for a polyp biomarker may improve polyp detection. Here we describe GE-137, a water-soluble probe consisting of a 26–amino acid cyclic peptide that binds the human tyrosine kinase c-Met conjugated to a fluorescent cyanine dye. Intravenous administration of GE-137 leads to its accumulation specifically in c-Met–expressing tumors in mice, and it is safe and well tolerated in humans. Fluorescence colonoscopy in patients receiving intravenous GE-137 enabled visualization of all neoplastic polyps that were visible with white light (38), as well as an additional nine polyps that were not visible with white light. This first-in-human pilot study shows that molecular imaging using an intravenous fluorescent agent specific for c-Met is feasible and safe, and that it may enable the detection of polyps missed by other techniques.

GNAS/Gnas encodes G(s)α that is mainly biallelically expressed but shows imprinted expression in some tissues. In Albright Hereditary Osteodystrophy (AHO) heterozygous loss of function mutations of GNAS can result in ectopic ossification that tends to be superficial and attributable to haploinsufficiency of biallelically expressed G(s)α. Oed-Sml is a point missense mutation in exon 6 of the orthologous mouse locus Gnas. We report here both the late onset ossification and occurrence of benign cutaneous fibroepithelial polyps in Oed-Sml. These phenotypes are seen on both maternal and paternal inheritance of the mutant allele and are therefore due to an effect on biallelically expressed G(s)α. The ossification is confined to subcutaneous tissues and so resembles the ossification observed with AHO. Our mouse model is the first with both subcutaneous ossification and fibroepithelial polyps related to G(s)α deficiency. It is also the first mouse model described with a clinically relevant phenotype associated with a point mutation in G(s)α and may be useful in investigations of the mechanisms of heterotopic bone formation. Together with earlier results, our findings indicate that G(s)α signalling pathways play a vital role in repressing ectopic bone formation.

There has been increased interest in the analysis of protein biomarkers in clinical tumor tissues in recent years. Tissue-based biomarker assays can add value and aid decision-making at all stages of drug development, as well as being developed for use as predictive biomarkers and for patient stratification and prognostication in the clinic. However, there must be an awareness of the legal and ethical issues related to the sourcing of human tissue samples. This article also discusses the limits of scope and critical aspects on the successful use of the following tissue-based methods: immunohistochemistry, tissue microarrays and automated image analysis. Future advances in standardization of tissue biobanking methods, immunohistochemistry and quantitative image analysis techniques are also discussed.