Dominique Figarella-Branger1, Emmanuèle Lechapt-Zalcman1, Emeline Tabouret1, Stephanie Jünger1, André Maues de Paula1, Corinne Bouvier1, Carole Colin1, Anne Jouvet1, Fabien Forest1, Felipe Andreiuolo1, Isabelle Quintin-Roue1, Marie-Christine Machet1, Anne Heitzmann1, Serge Milin1, Henri Sevestre1, Catherine Godfraind1, François Labrousse1, Philippe Metellus1, Didier Scavarda1, Torsten Pietsch1. 1. Department of Pathology and Neuropathology, Assistance Publique des Hôpitaux de Marseille (APHM), CHU Timone, Marseille, France (D.F.-B, E.T., A.M.d.P, C.B.); Aix-Marseille Université, Inserm, Marseille, France (D.F.-B, E.T., C.B., C.C.); Department of Pathology, CHU Caen, Hôpital de la Côte de Nacre, Caen, France (E.L.-Z); Department of Neurooncology, APHM, Marseille, France (E.T.); Department of Neuropathology, University of Bonn, Medical Center Sigmund-Freud, Bonn, Germany (S.J., T.P.); Department of Pathology and Neuropathology, Hospices civils de Lyon, Bron, France (A.J.); Department of Pathology, CHU de Saint-Etienne, Saint-Etienne, France (F.F.); Department of Neuropathology, CHU Sainte Anne, Paris, France (F.A.); Department of Pathology, CHU de Brest, Hôpital de la Cavale Blanche, Brest, France (I.Q.-R); Department of Pathology, CHU de Tours, Hôpital Trousseau, Tours, France (M.-C.M.); Department of Pathology, CHR d'Orléans, Hôpital de la Source, Orléans, France (A.H.); Department of Pathology, CHU de Poitiers, Hôpital la Milétrie, Poitiers, France (S.M.); Department of Pathology, CHU d'Amiens, Amiens, France (H.S.); Department of Pathology, CHU de Clermont-Ferrand, Clermont-Ferrand, France (C.G.); Department of Pathology, CHU de Limoges, Limoges, France (F.L.); Department of Neurosurgery, APHM, CHU Timone, Marseille, France (P.M.); Department of Pediatric Neurosurgery, APHM, CHU Timone, Marseille, France (D.S.).
Abstract
BACKGROUND: Clear cell ependymoma is one of the 4 main histological subtypes of ependymomas defined by the World Health Organization (WHO) classification of tumors of the CNS. DNA methylation profiling can distinguish 4 subgroups of intracranial ependymomas, including supratentorial (ST) ependymomas with Yes-associated protein 1 fusion (YAP1), ST ependymomas with fusion of v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA), posterior fossa ependymomas with balanced genome, and posterior fossa ependymomas with chromosomal instability. In addition, trisomy 19 is a genomic hallmark of ependymomas with rich branching capillaries. However, the relation of histological and molecular subtypes is unclear. METHODS: Here, we report a series of 20 ependymomas histologically defined by clear cells and branching capillaries. RESULTS: We observed a strong male predominance. Median age at surgery was 10.4 years (range, 0.8-68.4). All cases were ST, cortical, contrast enhancing, and most often frontal, cystic, and calcified. All tumors qualified as WHO grade III. Some of them exhibited neuronal differentiation. Trisomy 19 was recorded in 13 cases. All samples strongly accumulated p65RelA protein within nuclei, indicating pathological activation of the nuclear factor-kappaB pathway. We identified causative C11ORF95-RELA fusion in almost all cases. Median progression-free survival and overall survival were 11.4 years (95% CI: 5.1-17.8) and not reached, respectively. CONCLUSION: ST clear cell ependymomas with branching capillaries display characteristic clinicopathological features and are associated with pathological activation of nuclear factor-kappaB signaling, which may indicate a potential novel target for therapy in these patients.
BACKGROUND:Clear cell ependymoma is one of the 4 main histological subtypes of ependymomas defined by the World Health Organization (WHO) classification of tumors of the CNS. DNA methylation profiling can distinguish 4 subgroups of intracranial ependymomas, including supratentorial (ST) ependymomas with Yes-associated protein 1 fusion (YAP1), ST ependymomas with fusion of v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA), posterior fossa ependymomas with balanced genome, and posterior fossa ependymomas with chromosomal instability. In addition, trisomy 19 is a genomic hallmark of ependymomas with rich branching capillaries. However, the relation of histological and molecular subtypes is unclear. METHODS: Here, we report a series of 20 ependymomas histologically defined by clear cells and branching capillaries. RESULTS: We observed a strong male predominance. Median age at surgery was 10.4 years (range, 0.8-68.4). All cases were ST, cortical, contrast enhancing, and most often frontal, cystic, and calcified. All tumors qualified as WHO grade III. Some of them exhibited neuronal differentiation. Trisomy 19 was recorded in 13 cases. All samples strongly accumulated p65RelA protein within nuclei, indicating pathological activation of the nuclear factor-kappaB pathway. We identified causative C11ORF95-RELA fusion in almost all cases. Median progression-free survival and overall survival were 11.4 years (95% CI: 5.1-17.8) and not reached, respectively. CONCLUSION: ST clear cell ependymomas with branching capillaries display characteristic clinicopathological features and are associated with pathological activation of nuclear factor-kappaB signaling, which may indicate a potential novel target for therapy in these patients.
Authors: M Payet; C Conter; F Labrousse; A Maues De Paula; A Marabelle; D Figarella Branger; R Bouvier; D Frappaz Journal: Childs Nerv Syst Date: 2011-12-30 Impact factor: 1.475
Authors: D Figarella-Branger; M Civatte; C Bouvier-Labit; J Gouvernet; D Gambarelli; J C Gentet; G Lena; M Choux; J F Pellissier Journal: J Neurosurg Date: 2000-10 Impact factor: 5.115
Authors: Michael D Taylor; Helen Poppleton; Christine Fuller; Xiaoping Su; Yongxing Liu; Patricia Jensen; Susan Magdaleno; James Dalton; Christopher Calabrese; Julian Board; Tobey Macdonald; Jim Rutka; Abhijit Guha; Amar Gajjar; Tom Curran; Richard J Gilbertson Journal: Cancer Cell Date: 2005-10 Impact factor: 31.743
Authors: John-Paul Kilday; Ruman Rahman; Sara Dyer; Lee Ridley; James Lowe; Beth Coyle; Richard Grundy Journal: Mol Cancer Res Date: 2009-06-16 Impact factor: 5.852
Authors: Matthew Parker; Kumarasamypet M Mohankumar; Chandanamali Punchihewa; Ricardo Weinlich; James D Dalton; Yongjin Li; Ryan Lee; Ruth G Tatevossian; Timothy N Phoenix; Radhika Thiruvenkatam; Elsie White; Bo Tang; Wilda Orisme; Kirti Gupta; Michael Rusch; Xiang Chen; Yuxin Li; Panduka Nagahawhatte; Erin Hedlund; David Finkelstein; Gang Wu; Sheila Shurtleff; John Easton; Kristy Boggs; Donald Yergeau; Bhavin Vadodaria; Heather L Mulder; Jared Becksfort; Jared Becksford; Pankaj Gupta; Robert Huether; Jing Ma; Guangchun Song; Amar Gajjar; Thomas Merchant; Frederick Boop; Amy A Smith; Li Ding; Charles Lu; Kerri Ochoa; David Zhao; Robert S Fulton; Lucinda L Fulton; Elaine R Mardis; Richard K Wilson; James R Downing; Douglas R Green; Jinghui Zhang; David W Ellison; Richard J Gilbertson Journal: Nature Date: 2014-02-19 Impact factor: 49.962
Authors: Cristina R Antonescu; Yun-Shao Sung; Lei Zhang; Narasimhan P Agaram; Christopher D Fletcher Journal: Am J Surg Pathol Date: 2017-05 Impact factor: 6.394
Authors: Amr H Saleh; Nardin Samuel; Kyle Juraschka; Mohammad H Saleh; Michael D Taylor; Michael G Fehlings Journal: Nat Rev Cancer Date: 2022-01-14 Impact factor: 69.800
Authors: Andrea M Griesinger; Davis A Witt; Sydney T Grob; Sabrina R Georgio Westover; Andrew M Donson; Bridget Sanford; Jean M Mulcahy Levy; Randall Wong; Daniel C Moreira; John A DeSisto; Ilango Balakrishnan; Lindsey M Hoffman; Michael H Handler; Kenneth L Jones; Rajeev Vibhakar; Sujatha Venkataraman; Nicholas K Foreman Journal: Neuro Oncol Date: 2017-10-01 Impact factor: 12.300