The aberrant hypermethylation of BRCA1 promoter CpG islands induces the decreased expression of BRCA1 (Breast Cancer 1) protein. It can be detected in sporadic breast cancer without BRCA1 pathogenic variants, particularly in triple-negative breast cancers (TNBC). We investigated BRCA1 hypermethylation status (by methylation-specific polymerase chain reaction (MS-PCR) and MassARRAY^® assays), and BRCA1 protein expression using immunohistochemistry (IHC), and their clinicopathological significance in 248 chemotherapy-naïve TNBC samples. Fifty-five tumors (22%) exhibited BRCA1 promoter hypermethylation, with a high concordance rate between MS-PCR and MassARRAY^® results. Promoter hypermethylation was associated with reduced IHC BRCA1 protein expression (p = 0.005), and expression of Programmed death-ligand 1 protein (PD-L1) by tumor and immune cells (p = 0.03 and 0.011, respectively). A trend was found between promoter hypermethylation and basal marker staining (p = 0.058), and between BRCA1 expression and a basal-like phenotype. In multivariate analysis, relapse-free survival was significantly associated with N stage, adjuvant chemotherapy, and histological subtype. Overall survival was significantly associated with T and N stage, histology, and adjuvant chemotherapy. In addition, patients with tumors harboring BRCA1 promoter hypermethylation derived the most benefit from adjuvant chemotherapy. In conclusion, BRCA1 promoter hypermethylation is associated with TNBC sensitivity to adjuvant chemotherapy, basal-like features and PD-L1 expression. BRCA1 IHC expression is not a good surrogate marker for promoter hypermethylation and is not independently associated with prognosis. Association between promoter hypermethylation and sensitivity to Poly(ADP-ribose) polymerase PARP inhibitors needs to be evaluated in a specific series of patients.

Background: Liver transplantation (LT) remains a potentially haemorrhagic procedure whose perioperative bleeding and transfusion could be better monitored using point-of-care devices. Quantra^® is a device based on sonorheometry to assess whole blood clot formation. Our aims were to describe Quantra^® parameters during LT and to study their correlations with standard laboratory parameters, and to determine Quantra^® cut-off values for thrombocytopenia, hypofibrinogenemia and coagulation factors’ deficit. Methods: In 34 patients undergoing LT, blood samples were collected before surgical incision, 15 min after the beginning of the anhepatic phase, and 15 min after arterial revascularization of the graft. Results: Clotting time (CT) was well correlated with prothrombin (PT) ratio and activated partial thromboplastin time (aPTT) ratio. Platelet contribution to clot stiffness (PCS) was correlated with platelets (ρ = 0.82, p < 0.001) and fibrinogen contribution clot stiffness (FCS) with fibrinogen (Fg) (ρ = 0.74, p < 0.001). CT predicted a PT ratio < 30% with an area under the curve (AUC) of 0.93 (95% CI 0.87–0.98; p < 0.001). PCS predicted a platelet count < 50 G/L with an AUC of 0.87 (95% CI 0.76–0.98, p < 0.001). FCS predicted a Fg < 1.0, 1.2 or 1.5 g/L, with an AUC of 0.86 (95% CI 0.77–094, p < 0.001), 0.82 (95% CI 0.74–0.91, p < 0.001) and 0.88 (95% CI 0.82–0.95, p < 0.001), respectively. Conclusion: Quantra^® provides a rapid assessment of haemostasis during LT.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, projected to affect 55% globally by 2040. Up to one-third of NAFLD patients develop non-alcoholic steatohepatitis (NASH), with 40% progressing to fibrosis. However, there are currently few reliable tools to predict disease progression. Impaired mitochondrial dynamics, characterized by dysregulated fission, fusion, and mitophagy, have emerged as key events in NAFLD pathophysiology, contributing to hepatocyte death and inflammation. This study explored the transition from steatosis to NASH through transcriptomic analyses, including data from patients with steatosis and those with NASH at different fibrosis stages. By identifying a transcriptomic signature associated with disease progression, the study revealed increased expression of genes involved in mitochondrial dynamics in NASH compared to steatosis and during NASH-related fibrosis. Histological analyses highlighted the central role of Dynamin-related protein 1 (Drp1), a dynamin GTPase essential for mitochondrial fission and mitophagy. In human liver biopsies, Drp1 expression progressively increased from NAFLD to NASH and NASH-related fibrosis and cirrhosis, predominantly in Kupffer cells. These finding suggest Drp1 is a potential driver of the transition to more severe liver damage, making it a promising biomarker for NASH development and progression and a potential therapeutic target in metabolic disorders.

Liver metastases of breast cancer are frequent and can recur even after “complete/R0” resection in combination with systemic and hormonal treatments. The aim of this study was to analyze throughout repeat hepatectomies for liver metastases the evolution of PI3KCA gene mutational status. All liver metastases nodules (n = 70) from 19 women who underwent at least 2 liver resections were reexamined. DNA extraction from archived tumoral tissue was performed and the major ‘hot spot’ mutations in the helical and catalytic domains of PI3KCA have been analyzed using Massarray platform (Agena Bioscience) based on allelic discrimination PCR amplification followed by sensitive mass spectrometry detection. The two major somatic hot spot PI3KCA mutations were found in 27 (38.6%) nodules corresponding to 8 of the 19 patients (42%). The frequency of women whose breast cancer liver metastases (BCLM) carries PI3KCA mutations increased from the first to the third hepatectomy. Tumors carrying PI3KCA mutations are significantly larger and more frequently observed when resections were R0 compared to patients with no PI3KCA mutation. PI3KCA mutations are frequently observed in BCLM and persist along with the recurrence. Their identification in circulating tumor cells should become a useful biomarker in the routine practice of breast cancer management to prevent tumor recurrence and overcome the problems of intra- and inter-tumoral heterogeneity of the current biomarkers,

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Raphael Saffroy1, 2, Jean-François Morère2, 3, Nelly Bosselut1, 2, Pasquale F. Innominato3, 4, 5, 6, Jocelyne Hamelin1, 2, Jean Trédaniel7, Sophie Masse8, Véronique Dussaule-Duchatelle9, André Balaton9, 10, Pierre Validire11, Catherine Guettier12, Mohamed Bouchahda3, 13 and Antoinette Lemoine1, 2 1AP-HP, GH Paris-Sud, Hôpital Paul Brousse, Department of Biochiemistry and Oncogenetics, Platform Oncomolpath/INCa, Villejuif, France 2INSERM UMR-S 1193, Université Paris-Sud, Université Paris-Saclay, Villejuif, France 3AP-HP, GH Paris-Sud, Hôpital Paul Brousse, Department of Medical Oncology, Villejuif, France 4INSERM UMR-935, Université Paris-Sud, Hôpital Paul Brousse, Villejuif, France 5Cancer Chronotherapy Unit, Cancer Research Centre, Warwick Medical School, University of Warwick, Coventry, United Kingdom 6Department of Oncology, Queen Elizabeth Hospital Birmingham NHS Foundation Trust, Birmingham, United Kingdom 7Hôpital Saint Joseph, Department of Respiratory Medicine, Université Paris 5, Paris, France 8Groupe Hospitalier Nord Essonne, Department of Pathology, Longjumeau, France 9Hôpital Saint Joseph, Department of Pathology, Paris, France 10ACP Bievres-les Ulis, Department of Pathology, Les Ulis, France 11Institut Mutualiste Montsouris, Department of Pathology, Paris, France 12AP-HP, GH Paris-Sud, Hôpital Paul Brousse, Department of Pathology, Platform Oncomolpath/INCa, Villejuif, France 13Ramsay-GDS Clinique du Mousseau, Department of Medical Oncology, Evry, France Correspondence to: Antoinette Lemoine, email: antoinette.lemoine@aphp.fr Keywords: NSCLC, genetic testing, genotype, EGFR, ERBB2 Received: November 01, 2016 Accepted: January 09, 2017 Published: February 07, 2017