Multicenter Evaluation of the Fully Automated PCR-Based Idylla EGFR Mutation Assay on Forman-Fixed, Paraffin-Embedded Tissue of Human Lung Cancer

Before initiating treatment of advanced non-small-cell lung cancer with tyrosine kinase inhibitors (eg, erlotinib, gefitinib, osimertinib, and afatinib), which inhibit the catalytic activity of epidermal growth factor receptor (EGFR), clinical guidelines require determining the EGFR mutational status for activating (EGFR exons 18, 19, 20, or 21) and resistance (EGFR exon 20) mutations. The EGFR resistance mutation T790M should be monitored at cancer progression. The Idylla EGFR Mutation Assay, performed on the Idylla molecular diagnostics platform, is a fully automated (<2.5 hours turnaround time) sample-to-result molecular test to qualitatively detect 51 EGFR oncogene point mutations, deletions, or insertions. In a 15-center evaluation, Idylla results on 449 archived formalin-fixed, paraffin-embedded tissue sections, originating from non-small-cell lung cancer biopsies and resection specimens, were compared with data obtained earlier with routine reference methods, including next-generation sequencing, Sanger sequencing, pyrosequencing, mass spectrometry, and PCR-based assays. When results were discordant, a third method of analysis was performed, when possible, to confirm test results. After confirmation testing and excluding invalids/errors and discordant results by design, a concordance of 97.6% was obtained between Idylla and routine test results. Even with <10 mm(2) of tissue area, a valid Idylla result was obtained in 98.9% of the cases. The Idylla EGFR Mutation Assay enables sensitive detection of most relevant EGFR mutations in concordance with current guidelines, with minimal molecular expertise or infrastructure

Inactivation par ARN interférence de la synthèse de deux cytokines impliquées dans la myélofibrose primitive (TGF-ß1 et IL-1a)

PARIS-BIUP (751062107) / SudocSudocFranceF

A 4-Year Retrospective Analysis of Salivary Gland Cytopathology Using the Milan System for Reporting Salivary Gland Cytology and Ancillary Studies

The cytopathology of salivary glands presents major challenges due to the heterogeneity of benign and malignant neoplasms, which is reflected in the large range of WHO 2017 Classifications. Fine needle aspiration (FNA) of salivary gland tumours is still the favoured initial approach as it results in good sensitivity and specificity. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was published in 2018 and comprises seven categories. We report results from a 4-year retrospective analysis of 328 salivary gland FNAs which were reviewed and classified according to the MSRSGC. We assess the risk of neoplasm, the risk of malignancy and the contribution of ancillary studies to the diagnosis. Benign neoplasms were the most frequent diagnosis (44.2%). Malignant and suspicious for malignancy were identified in 11.3% and 4.9% of diagnosed cases, respectively. Histopathological analysis after surgery was available for 216 (65.8%) of the cases. All malignant cases were confirmed post-surgery, and 68.8% of suspicious for malignancy were confirmed as malignant tumours. Immunocytochemistry was informative in 72.3% of cases. Immunocytochemistry and FISH provided the definitive diagnosis in 23.7% and 33% of cases, respectively. In conclusion, the MSRSGC is more effective when specific features of neoplasms can be identified. Ancillary studies help to further characterise salivary gland tumours and thereby increase the accuracy of MSRSGC

Impact of Regorafenib on Endothelial Transdifferentiation of Glioblastoma Stem-like Cells

Glioblastomas (GBM) are aggressive brain tumours with a poor prognosis despite heavy therapy that combines surgical resection and radio-chemotherapy. The presence of a subpopulation of GBM stem cells (GSC) contributes to tumour aggressiveness, resistance and recurrence. Moreover, GBM are characterised by abnormal, abundant vascularisation. Previous studies have shown that GSC are directly involved in new vessel formation via their transdifferentiation into tumour-derived endothelial cells (TDEC) and that irradiation (IR) potentiates the pro-angiogenic capacity of TDEC via the Tie2 signalling pathway. We therefore investigated the impact of regorafenib, a multikinase inhibitor with anti-angiogenic and anti-tumourigenic activity, on GSC and TDEC obtained from irradiated GSC (TDEC IR+) or non-irradiated GSC (TDEC). Regorafenib significantly decreases GSC neurosphere formation in vitro and inhibits tumour formation in the orthotopic xenograft model. Regorafenib also inhibits transdifferentiation by decreasing CD31 expression, CD31+ cell count, pseudotube formation in vitro and the formation of functional blood vessels in vivo of TDEC and TDEC IR+. All of these results confirm that regorafenib clearly impacts GSC tumour formation and transdifferentiation and may therefore be a promising therapeutic option in combination with chemo/radiotherapy for the treatment of highly aggressive brain tumours

A single-cell expression atlas of clear cell renal cell carcinoma

National audienc

Rapid and Efficient Production of Human Functional Mast Cells through a Three-Dimensional Culture of Adipose Tissue–Derived Stromal Vascular Cells

International audienc

Multicenter evaluation of the fully automated PCR-based Idylla EGFR Mutation Assay on formalin-fixed, paraffin-embedded Q1 tissue of human lung cancer

Before initiating treatment of advanced nonesmall-cell lung cancer with tyrosine kinase inhibitors (eg, erlotinib, gefitinib, osimertinib, and afatinib), which inhibit the catalytic activity of epidermal growth factor receptor (EGFR), clinical guidelines require determining the EGFR mutational status for activating (EGFR exons 18, 19, 20, or 21) and resistance (EGFR exon 20) mutations. The EGFR resistance mutation T790M should be monitored at cancer progression. The Idylla EGFR Mutation Assay, performed on the Idylla molecular diagnostics platform, is a fully automated (<2.5 hours turnaround time) sample-to-result molecular test to qualitatively detect 51 EGFR oncogene point mutations, deletions, or insertions. In a 15- center evaluation, Idylla results on 449 archived formalin-fixed, paraffin-embedded tissue sections, originating from nonesmall-cell lung cancer biopsies and resection specimens, were compared with data obtained earlier with routine reference methods, including next-generation sequencing, Sanger sequencing, pyrosequencing, mass spectrometry, and PCR-based assays. When results were discordant, a third method of analysis was performed, when possible, to confirm test results. After confirmation testing and excluding invalids/errors and discordant results by design, a concordance of 97.6% was obtained between Idylla and routine test results. Even with <10 mm2 of tissue area, a valid Idylla result was obtained in 98.9% of the cases. The Idylla EGFR Mutation Assay enables sensitive detection of most relevant EGFR mutations in concordance with current guidelines, with minimal molecular expertise or infrastructure

Effets des engins de pêche sur les fonds marins de Manche-Est et du golfe normand-breton

Fishing professionals in Normandy and Hauts-de-France have initiated the IPREM project (Impact des engins de Pêche sur les fonds marins et la Résilience Ecologique du Milieu) with the aim of conducting a bibliographic review of the impact of towed gear in contact with the seabed on benthic communities and habitats, specific to the waters of the Channel. The fishing gears considered are the dredge (DRB), otter trawl (OTB), beam trawl (TBB) and Scottish and Danish seines (SSC and SDN respectively). To characterize the impact on the habitats, the fishing effort to which each habitat is subjected and their sensitivity were considered. The most impacted habitat is offshore circalittoral sand, followed by offshore circalittoral coarse sediment, circalittoral sand and circalittoral coarse sediment. The fact that the Channel is a sea with strong hydrodynamics may confer a stronger resistance to the benthic communities present. This could explain why, over the years, no major changes in habitats have been observed. However, it must be taken into account that the Channel is a highly anthropized sea that has been intensively fished for decades. The communities present reflect the species assemblages that have been able to resist this high fishing pressure. Measures to reduce the impact are nevertheless necessary and must be supported by scientific work taking into account the interests and needs of fishing professionals.Les professionnels de la pêche en Normandie et Hauts-de-France ont initié le projet IPREM (Impact des engins de Pêche sur les fonds marins et la Résilience Ecologique du Milieu) avec pour but de faire un état des lieux bibliographique de l'impact des arts traînants en contact avec le fond marin sur les communautés et habitats benthiques, spécifiques aux eaux de la Manche. Les engins de pêche considérés sont la drague (DRB), le chalut à panneaux (OTB), le chalut à perche (TBB) et les sennes écossaises et danoises (SSC et SDN respectivement). Pour caractériser l'impact sur les habitats, l'effort de pêche auquel est soumis chaque habitat et leur sensibilité ont été pris en considération. L'habitat le plus impacté est le sable circalittoral au large, suivi du sédiment grossier circalittoral au large, du sable circalittoral et du sédiment grossier circalittoral. Le fait que la Manche soit une mer à fort hydrodynamisme peut conférer une résistance plus forte aux communautés benthiques présentes. Cela pourrait expliquer qu’au fil des années, il n'a pas été observé de grands changements au niveau des habitats. Cependant, il faut prendre en compte que la Manche est une mer très anthropisée et intensément pêchée depuis des dizaines d’années. Les communautés présentes reflètent les assemblages d’espèces ayant pu résister à cette pression de pêche élevée. Des mesures pour réduire l’impact sont néanmoins nécessaires et doivent être appuyées sur un travail scientifique prenant en compte les intérêts et besoins des professionnels de la pêche