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1. Myocardial infarction during giant cell arteritis: A cohort study

Author

Tibor Ponnelle, Sylvain Audia, Bernard Bonnotte, G. Muller, Alain Putot, Georges Tarris, André Ramon, Maxime Samson, Yves Cottin, Eric Steinmetz, Marianne Zeller, Nicolas Falvo, Béatrice Terriat, Maud Maza, Laurent Martin, Hélène Greigert, Catherine Creuzot-Garcher, Louis Arnould, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Physiopathologie et épidémiologie cérébro-cardiovasculaire [Dijon] (PEC2), Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Cypath [Dijon], Cypath : siège social [Villeurbanne], and The University Hospital of Dijon, the Association de Cardiologie de Bourgogne, and by grants from the Agence Regionale de Sante (ARS) de Bourgogne Franche-Comte, and from the Regional Council of Bourgogne Franche-Comte.

Subjects
medicine.medical_specialty, Population, Coronary Artery Disease, 030204 cardiovascular system & hematology, Cohort Studies, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, immune system diseases, Prednisone, Internal medicine, Internal Medicine, medicine, Humans, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, skin and connective tissue diseases, education, education.field_of_study, population study, giant cell arteritis, business.industry, medicine.disease, 3. Good health, Giant cell arteritis, myocardial infarction, Cohort, cardiovascular system, Cardiology, Population study, France, business, medicine.drug, Cohort study
Abstract

International audience; BACKGROUND: Cardiovascular risk is increased in giant cell arteritis (GCA). We aimed to characterize myocardial infarction (MI) in a GCA cohort, and to compare the GCA and non-GCA population affected by MI. METHODS: In patients with a biopsy-proven diagnosis of GCA between 1 January 2001 and 31 December 2016 in Côte D'Or (France), we identified patients with MI by crossing data from the territorial myocardial infarction registry (Observatoire des Infarctus de Côte d'Or) database. Five controls (non-GCA + MI) were paired with one case (GCA + MI) after matching for age, sex, cardiovascular risk factors and prior cardiovascular disease. MI were characterized as type 1 MI (T1MI), resulting from thrombus formation due to atherothrombotic disease, or type 2 MI (T2MI), due to a myocardial supply/demand mismatch. GCA-related MI was defined as MI occurring within 3 months of a GCA flare (before or after). RESULTS: Among 251 biopsy-proven GCA patients, 13 MI cases were identified and paired with 65 controls. MI was GCA-related in 6/13 cases, accounting for 2.4% (6/251) of our cohort. T2MI was more frequently GCA-related than GCA-unrelated (80% vs. 16.7%, p = 0.080), and GCA diagnosis was the only identified triggering factor in 75% of GCA-related T2MI. GCA-unrelated MI were more frequently T1MI and occurred in patients who had received a higher cumulative dose of prednisone (p = 0.032). GCA was not associated with poorer one-year survival. CONCLUSIONS: GCA-related MI are mainly T2MI probably caused by systemic inflammation rather than coronaritis. GCA-unrelated MI are predominantly T1MI associated with atherothrombotic coronary artery disease.

Published
2021
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2. Hematological malignancies in giant cell arteritis: a french population-based study

Author

Bernard Bonnotte, Georges Tarris, André Ramon, Maxime Samson, Morgane Mounier, Sylvain Audia, Marc Maynadié, Hélène Greigert, Louis Arnould, Catherine Creuzot-Garcher, Laurent Martin, Tibor Ponnelle, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Registre des hémopathies malignes de Côte d'Or, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Ophtalmologie (CHU de Dijon), Cypath [Dijon], Cypath : siège social [Villeurbanne], Service d'hématologie biologique (CHU de Dijon), Julien, Sabine, and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Myeloid, Population, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, immune system diseases, Internal medicine, Epidemiology, medicine, Humans, Pharmacology (medical), cardiovascular diseases, hematological malignancies, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, education, skin and connective tissue diseases, Retrospective Studies, 030203 arthritis & rheumatology, education.field_of_study, business.industry, giant cell arteritis, Incidence, Incidence (epidemiology), Middle Aged, medicine.disease, 3. Good health, Population based study, Giant cell arteritis, 030104 developmental biology, medicine.anatomical_structure, Increased risk, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, population-based study, Hematologic Neoplasms, cardiovascular system, Female, France, business
Abstract

Objectives An increased risk of haematological malignancies (HM) has been reported in GCA patients. Our study aimed to investigate the incidence and the type of HM occurring in GCA. Methods All patients with GCA and HM living in Côte d’Or (France) were identified by crossing data from the RHEMCO (Registre des Hémopathies Malignes de Côte d’Or) and those having a positive temporal artery biopsy between 1 January 2001 and 31 December 2018. Results Among 276 biopsy-proven GCA patients, 14 HM were identified in 12 patients (4.3%). In comparison with the general population aged >50 y, the incidence of myeloid HM and myeloproliferative syndromes were increased in GCA patients [standardized incidence ratios (SIR) = 2.71 and 5.16, respectively], with a specific increase in men with GCA (SIR = 4.82 and 9.04, respectively) but not in women. In addition, the study of SIR depending on the chronology between GCA and HM diagnoses suggests that there was an increased risk of developing GCA in men but not in women, after a diagnosis of myeloid HM (SIR = 9.56), especially if it was a MPS (SIR = 17.56). Conclusions Our study shows a particular epidemiology of HM in GCA patients, which is characterized by an increased incidence of myeloid HM, especially MPS, in male GCA patients. The chronology of the diagnoses of GCA and HM raises the hypothesis that clonal hematopoiesis may be implicated in some cases of GCA.

Published
2021
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3. MiR-31-3p do not predict anti-EGFR efficacy in first-line therapy of RAS wild-type metastatic right-sided colon cancer

Author

Emeric Boisteau, Alexandra Lespagnol, Marie De Tayrac, Sébastien Corre, Anthony Perrot, Nathalie Rioux-Leclercq, Séverine Martin-Lannerée, Pascal Artru, Philippe Chalabreysse, Pierre-Guillaume Poureau, Laurent Doucet, Dahna Coupez, Jaafar Bennouna, Céline Bossard, Romain Coriat, Frédéric Beuvon, Lucile Bauguion, François Leclair, Romain Chautard, Thierry Lecomte, Serge Guyetant, Romain Desgrippes, Denis Grasset, Hélène Lhostis, Karine Bouhier-Leporrier, Frédéric Bibeau, Julien Edeline, Marie-Dominique Galibert, Astrid Lièvre, CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), IntegraGen, Hôpital privé Jean Mermoz [Lyon], Cypath : siège social [Villeurbanne], University Hospital Gasthuisberg, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Départemental Vendée (CHDV), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CH de Saint-Malo [Broussais], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire [Rennes], CRLCC Eugène Marquis (CRLCC), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogenesis, Stress, Signaling (OSS), This research received no external funding. We thank the Rennes University Hospital and the Centre d'Etude des Maladies Digestives de Rennes (CEMDR) for their financial support. Anthony Perrot was financially supported by the Rennes University Hospital., Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University Hospital Gasthuisberg [Leuven], and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Hepatology, [SDV]Life Sciences [q-bio], Gastroenterology, colorectal cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.CAN]Life Sciences [q-bio]/Cancer, miR-31-3p, anti-EGFR mAb, Bevacizumab, ErbB Receptors, MicroRNAs, Antineoplastic Combined Chemotherapy Protocols, Colonic Neoplasms, biomarker, metastasis, Humans, Colorectal Neoplasms, Retrospective Studies
Abstract

International audience; BACKGROUND: Low miR-31-3p expression was identified as predictive of anti-EGFR efficacy in RAS-wt mCRC. Primary tumor side was also proposed as a predictive factor of anti-EGFR benefit. This retrospective multicentric study evaluated the predictive role of miR-31-3p in right-sided RAS-wt mCRC patients treated with first-line CT+anti-EGFR or CT+bevacizumab (Beva). METHODS: Seventy-two right-sided RAS-wt mCRC patients treated in first-line with CT+anti-EGFR (n=43) or Beva (n=29) were included. Overall survival (OS), progression-free survival (PFS) and response rate (RR) were analyzed and stratified according to tumor miR-31-3p expression level and targeted therapy (TT). RESULTS: BRAF V600E mutation was more frequent in high vs low miR-31-3p expressers (60.6% vs 15.4%, P < 0.001). PFS was significantly longer with CT+Beva than with CT+anti-EGFR (13 vs 7 months; P = 0.024). Among low miR-31-3p expressers, PFS, OS and RR were not significantly different between the two groups, while in high miR-31-3p expressers, only PFS was longer in the CT+Beva group (11 vs 6 months; P = 0.03). In patients treated with CT+anti-EGFR, low miR-31-3p expressers had a significantly longer OS (20 vs 13 months; P = 0.02) than high miR-31-3p expressers. ORR was not significantly different between the two groups of treatment, in both low and high miR-31-3p expressers. MiR-31-3p expression status was statistically correlated between primary tumors and corresponding metastases. CONCLUSION: In this study, miR-31-3p couldn’t identify a subgroup of patients with right-sided RAS-wt mCRC who might benefit from anti-EGFR and suggest that Beva is the TT of choice in first-line treatment of these patients.

Published
2021
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4. Morphologic features in a series of 352 Spitz melanocytic proliferations help predict their oncogenic drivers

Author

Mahtab Samimi, Julien Jacquemus, Daniel Pissaloux, Franck Tirode, Arnaud de la Fouchardière, Thibault Kervarrec, Christine Castillo, Département d'anatomopathologie, biopathologie, Centre Léon Bérard [Lyon], Département de Pathologie [CHRU Tours], Université Francois Rabelais [Tours]-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Infectiologie et Santé Publique (UMR ISP), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Cypath : siège social [Villeurbanne], Université Francois Rabelais [Tours]-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)

Subjects
Proto-Oncogene Proteins B-raf, Morphology, Pathology, medicine.medical_specialty, Skin Neoplasms, Spitz naevus, Carcinogenesis, Biology, MAP3K8, Pathology and Forensic Medicine, Oncogenic driver, 03 medical and health sciences, 0302 clinical medicine, Stroma, Proto-Oncogene Proteins, medicine, ROS1, Humans, Child, Fusion, Molecular Biology, Cellular atypia, 030304 developmental biology, 0303 health sciences, Melanoma, Receptor Protein-Tyrosine Kinases, Cell Biology, General Medicine, Protein-Tyrosine Kinases, medicine.disease, 030220 oncology & carcinogenesis, Spitz melanocytic proliferation, Immunohistochemistry, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract

International audience; Spitz nevi are indolent melanocytic tumors arising preferentially during and after childhood. Over the last decades, recurrent oncogenic drivers, sparsely detected in melanoma, were identified in Spitz melanocytic proliferations. Therefore, the detection of such drivers appears as a relevant diagnostic tool to distinguish both entities. Interestingly, morphologic features might correlate with the oncogenic drivers. Thus, the goal of this study was to assess the performances of previously identified morphological criteria to predict the presence of specific drivers. In total, 352 Spitz melanocytic proliferations either with a genetically identified oncogenic driver or investigated for ALK, ROS1, and NTRK1 overexpression by immunohistochemistry were enrolled in the present study. The microscopic features of the cases were assessed blindly with regards to the molecular status and, performances of previously described morphological criteria to predict the molecular status were assessed applying the likelihood-ratio test (LHR). Overall, an oncogenic driver was identified in 76% of the cases (n = 268/352). No microscopic features allowed the reliable prediction of ROS1- and NTRK1-overexpressing cases. By contrast, a plexiform pattern can contribute to the recognition of ALK-overexpressing cases (LHR(+) = 6.14). Importantly, the pseudo-schwannoma variant was highly suggestive of NTRK3-rearranged cases (LHR(+) = 43). Moreover, atypical/malignant tumor (LHR(+) = 5.18), severe cellular atypia (LHR(+) = 5.07), and p16 loss (LHR(+) = 14) contribute to the recognition of MAP3K8-rearranged cases, while the presence of a sheet-like architecture (LHR(+) = 5.39) and a marked fibrosis of the stroma (LHR(+)=5.06) were predictive of BRAF-fused tumors. To conclude, our study confirms ALK-overexpressing, NTRK3-, MAP3K8-, and BRAF-rearranged cases harbored distinct morphologic features allowing their microscopic recognition.

Published
2021
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5. Rapid detection of EGFR mutations in decalcified lung cancer bone metastasis

Author

Guillaume Pontarollo, Jean-Baptiste Pialat, Nicolas Girard, Marie Brevet, Emmanuel Watkin, Fabien Forest, Cyrille B. Confavreux, Antoine Boureille, Violaine Yvorel, Sylvie Isaac, Carole Ferraro-Peyret, Duchange, Nathalie, Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Cypath : siège social [Villeurbanne], Institut du thorax, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ciblage thérapeutique en Oncologie (EA3738), and Université de Lyon-Université de Lyon

Subjects
0301 basic medicine, lcsh:Diseases of the musculoskeletal system, medicine.drug_class, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Tyrosine kinase inhibitor, medicine.disease_cause, lcsh:RC254-282, DNA sequencing, Tyrosine-kinase inhibitor, 03 medical and health sciences, Exon, symbols.namesake, 0302 clinical medicine, medicine, Lung carcinoma, Lung cancer, ComputingMilieux_MISCELLANEOUS, Sanger sequencing, Mutation, business.industry, Bone metastases, Bone metastasis, Ion semiconductor sequencing, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 030104 developmental biology, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Oncology, Decalcification, 030220 oncology & carcinogenesis, Cancer research, symbols, lcsh:RC925-935, EGFR mutation, business
Abstract

Detection of molecular alterations in lung cancer bone metastasis (LCBM) is particularly difficult when decalcification procedure is needed. The Idylla™ real-time (RT)-PCR is compared to the routine method used in our laboratory, which combines next generation and Sanger sequencing, for the detection of EGFR mutations in LCBM.LCBM subjected to EDTA or formic acid decalcification were analysed for EGFR mutational status using two methods: first, the Ion Torrent Ampliseq next generation sequencing (NGS) assay +/- Sanger sequencing was used prospectively; then, the fully-automated, RT-PCR based molecular testing system Idylla™ EGFR Mutation Test was applied retrospectively.Out of the 34 LCBM assayed, 14 (41.2%) were unsuitable for NGS analysis and five remained unsuitable after additional Sanger EGFR sequencing (5/34, 14.7%). Using Idylla™, valid results were observed for 33/34 samples (97.1%). The concordance between the NGS +/- Sanger sequencing method and the RT-PCR method was 89.7% (26/29), one false positive EGFR S768I mutation and two false negative results were observed using Idylla™; one of these false negative cases was diagnosed by Sanger sequencing with a rare exon 19 EGFR mutation not covered by the Idylla™ EGFR Mutation Test design.Detection of EGFR mutations in decalcified LCBM is challenging using NGS, more than half of samples showing invalid results. Alternative methods should thus be preferred to spare clinical samples and decrease delay. The Idylla™ EGFR Mutation Test shows a good performance on decalcified bone samples and could be used as a first step. In case of negative results, a sequencing approach is mandatory to check the presence of rare EGFR mutations sensitive to EGFR tyrosine kinase inhibitors. Keywords: Lung carcinoma, EGFR mutation, Bone metastases, Decalcification, Tyrosine kinase inhibitor

Published
2020
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