Novel immunohistochemistry-based signatures to predict metastatic site of triple-negative breast cancers

Background: Although distant metastasis (DM) in breast cancer (BC) is the most lethal form of recurrence and the most commonunderlying cause of cancer related deaths, the outcome following the development of DM is related to the site of metastasis.Triple negative BC (TNBC) is an aggressive form of BC characterised by early recurrences and high mortality. Athough multiplevariables can be used to predict the risk of metastasis, few markers can predict the specific site of metastasis. This study aimed atidentifying a biomarker signature to predict particular sites of DM in TNBC.Methods: A clinically annotated series of 322 TNBC were immunohistochemically stained with 133 biomarkers relevant to BC, todevelop multibiomarker models for predicting metastasis to the bone, liver, lung and brain. Patients who experienced metastasisto each site were compared with those who did not, by gradually filtering the biomarker set via a two-tailed t-test and Coxunivariate analyses. Biomarker combinations were finally ranked based on statistical significance, and evaluated in multivariableanalyses.Results: Our final models were able to stratify TNBC patients into high risk groups that showed over 5, 6, 7 and 8 times higher riskof developing metastasis to the bone, liver, lung and brain, respectively, than low-risk subgroups. These models for predictingsite-specific metastasis retained significance following adjustment for tumour size, patient age and chemotherapy status.Conclusions: Our novel IHC-based biomarkers signatures, when assessed in primary TNBC tumours, enable prediction of specificsites of metastasis, and potentially unravel biomarkers previously unknown in site tropism

lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. Cooperation between DNA, RNA and protein regulates gene expression and controls differentiation through interactions that connect regions of nucleic acids and protein domains and through the assembly of biomolecular condensates. Here, we report that endoderm differentiation is regulated by the interaction between the long non-coding RNA (lncRNA) DIGIT and the bromodomain and extraterminal domain protein BRD3. BRD3 forms phase-separated condensates of which the formation is promoted by DIGIT, occupies enhancers of endoderm transcription factors and is required for endoderm differentiation. BRD3 binds to histone H3 acetylated at lysine 18 (H3K18ac) in vitro and co-occupies the genome with H3K18ac. DIGIT is also enriched in regions of H3K18ac, and the depletion of DIGIT results in decreased recruitment of BRD3 to these regions. Our findings show that cooperation between DIGIT and BRD3 at regions of H3K18ac regulates the transcription factors that drive endoderm differentiation and suggest that protein–lncRNA phase-separated condensates have a broader role as regulators of transcription

Right hepatic arterial pseudoaneurysm with hemobilia following minilaparotomy cholecystectomy: A rare complication

Hepatic arterial pseudoaneurysm with hemobilia occurs less frequently as a complication of minilaparotomy cholecystectomy than laparoscopic cholecystectomy; however, given its severe nature, it needs to be managed promptly. This report presents a case of right hepatic artery pseudoaneurysm with hemobilia in a 36-year-old woman who underwent minilaparotomy cholecystectomy 5 weeks earlier. Angiography with embolization was carried out as definitive treatment