Ki‐67 and MCM6 labeling indices are correlated with overall survival in anaplastic oligodendroglioma, IDH1‐mutant and 1p/19q‐codeleted: a multicenter study from the French POLA network

Autor: Celso Pouget, Sébastien Hergalant, Emilie Lardenois, Stéphanie Lacomme, Rémi Houlgatte, Catherine Carpentier, Caroline Dehais, Fabien Rech, Luc Taillandier, Marc Sanson, Romain Appay, Carole Colin, Dominique Figarella‐Branger, Shyue‐Fang Battaglia‐Hsu, Guillaume Gauchotte, Christine Desenclos, H. Sevestre, Philippe Menei, A. Rousseau, T. Cruel, S. Lopez, M.I. Mihai, A. Petit, R. Seizeur, I. Quintin‐Roué, C. Adam, F. Parker, S. Eimer, H. Loiseau, L. Bekaert, F. Chapon, D. Ricard, C. Godfraind, T. Khallil, D. Cazals‐Hatem, T. Faillot, C. Gaultier, M. C Tortel, I. Carpiuc, P. Richard, W. Lahiani, H. Aubriot‐Lorton, F. Ghiringhelli, C‐A Maurage, E. Le Rhun, E. M. Gueye, F. Labrousse, F. Ducray, D. Meyronet, O. Chinot, L. Bauchet, V. Rigau, P. Beauchesne, M. Campone, D. Loussouarn, D. Fontaine, F. Vandenbos‐Burel, A. Le. Floch, P. Roger, C. Blechet, M. Fesneau, A. Carpentier, A. Idbaih, J. Y. Delattre, K. Mokhtari, F. Bielle, S. Hamdi, M. Polivka, S. Milin, P. Colin, M. D. Diebold, D. Chiforeanu, E. Vauleon, O. Langlois, A. Laquerriere, F. Forest, M. J. Motso‐Fotso, M. Andraud, G. Runavot, B. Lhermitte, G. Noel, S. Gaillard, C. Villa, N. Desse, C. Rousselot‐Denis, I. Zemmoura, E. Cohen‐Moyal, E. Uro‐Coste, F. Dhermain
Přispěvatelé: Service de Pathologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre de Ressources Biologiques - [Nancy] (CRB Nancy), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurochirurgie [CHRU Nancy], Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de neurologie [CHRU Nancy], OncoNeuroTek [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Laboratoire d'Anatomie Pathologique-Neuropathologique [AP-HM Hôpital La Timone], Hôpital de la Timone [CHU - APHM] (TIMONE), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université - Département de neurologie 2 - Mazarin, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP]
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Proliferation index
[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
0302 clinical medicine
Research Articles
Aged
80 and over
Brain Neoplasms
General Neuroscience
[SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular Networks [q-bio.MN]
Middle Aged
Prognosis
Isocitrate Dehydrogenase
3. Good health
Survival Rate
Microglial cell activation
Ki-67
Immunohistochemistry
Female
France
[STAT.ME]Statistics [stat]/Methodology [stat.ME]
Adult
IDH1
Mitotic index
Oligodendroglioma
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
Postsynaptic specialization
Pathology and Forensic Medicine
03 medical and health sciences
Young Adult
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Glioma
[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
[SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
medicine
Mitotic Index
Humans
Aged
[INFO.INFO-DB]Computer Science [cs]/Databases [cs.DB]
Gene Expression Profiling
medicine.disease
Minichromosome Maintenance Complex Component 6
030104 developmental biology
Ki-67 Antigen
Mutation
biology.protein
Cancer research
Neurology (clinical)
[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
030217 neurology & neurosurgery
Gene Deletion
Zdroj: Brain Pathol
Brain Pathology
Brain Pathology, 2020, 30 (3), pp.465-478. ⟨10.1111/bpa.12788⟩
Brain Pathology, Wiley, 2020, 30 (3), pp.465-478. ⟨10.1111/bpa.12788⟩
ISSN: 1015-6305
1750-3639
Popis: International audience; Anaplastic oligodendroglioma (AO), IDH‐mutant and 1p/19q codeleted (IDHmut+/1p19qcodel), is a high‐grade glioma with only limited prognostic markers. The primary objective of this study was to evaluate, by immunohistochemistry, the prognostic value of two proliferation markers, MCM6 and Ki‐67, in a large series of IDHmut+/1p19qcodel AO included in the POLA (“Prise en charge des Oligodendrogliomes Anaplasiques”) French national multicenter network. We additionally examined the transcriptome obtained from this series to understand the functional pathways dysregulated with the mRNA overexpression of these two markers. The labelling indices (LI) of MCM6 and Ki‐67 were obtained via computer‐assisted color image analyses on immunostained AO tissues of the cohort (n=220). Furthermore, a subgroup of AO (n=68/220) was used to perform transcriptomic analyses. A high LI of either MCM6 (≥50%) or Ki‐67 (≥ 15%) correlated with shorter overall survival, both in univariate (P=0.013 and P=0.004, respectively) and multivariate analyses (P=0.027; multivariate Cox model including age, mitotic index, MCM6 and Ki‐67). MCM6 and Ki‐67 LI also correlated with overall survival in an additional retrospective cohort of 30 grade II IDHmut+/1p19qcodel oligodendrogliomas. The prognostic value of MCM6 mRNA level was confirmed in The Cancer Genome Atlas (TCGA) IDHmut+/1p19qcodel gliomas. The transcriptomic approach revealed that high transcriptional expressions of MCM6 and MKI67 were both linked positively with cell cycle progression, DNA replication, mitosis, pro‐neural phenotype as well as neurogenesis, and negatively with microglial cell activation, immune response, positive regulation of myelination, oligodendrocyte development, beta‐amyloid binding, and postsynaptic specialization.In conclusion, the overexpression of MCM6 and/or Ki‐67 is independently associated to shorter overall survival in IDHmut+/1p19qcodel AO. These two easy‐to‐use and cost‐effective markers could thus be used concurrently in routine pathology practice. Additionally, the transcriptomic analyses showed that AO with high proliferation index have down‐regulated immune response and lower microglial cells activation, and bears pro‐neural phenotype.
Databáze: OpenAIRE
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