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Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome.
Panwalkar, Pooja; Clark, Jonathan; Ramaswamy, Vijay; Hawes, Debra; Yang, Fusheng; Dunham, Christopher; Yip, Stephen; Hukin, Juliette; Sun, Yilun; Schipper, Matthew J; Chavez, Lukas; Margol, Ashley; Pekmezci, Melike; Chung, Chan; Banda, Adam; Bayliss, Jill M; Curry, Sarah J; Santi, Mariarita; Rodriguez, Fausto J; Snuderl, Matija; Karajannis, Matthias A; Saratsis, Amanda M; Horbinski, Craig M; Carret, Anne-Sophie; Wilson, Beverly; Johnston, Donna; Lafay-Cousin, Lucie; Zelcer, Shayna; Eisenstat, David; Silva, Marianna; Scheinemann, Katrin; Jabado, Nada; McNeely, P Daniel; Kool, Marcel; Pfister, Stefan M; Taylor, Michael D; Hawkins, Cynthia; Korshunov, Andrey; Judkins, Alexander R; Venneti, Sriram.
  • Panwalkar P; Department of Pathology, University of Michigan, Ann Arbor, MI, 48104, USA.
  • Clark J; Department of Pathology, University of Michigan, Ann Arbor, MI, 48104, USA.
  • Ramaswamy V; Division of Haematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
  • Hawes D; Programme in Neuroscience and Mental Health, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
  • Yang F; Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, 4650 Sunset Boulevard, MS #43, Los Angeles, CA, 90027, USA.
  • Dunham C; Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, 4650 Sunset Boulevard, MS #43, Los Angeles, CA, 90027, USA.
  • Yip S; Division of Anatomic Pathology, British Columbia Children's Hospital, 4500 Oak Street, Vancouver, BC, V6H 3N1, Canada.
  • Hukin J; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, V6T1Z3, BC, Canada.
  • Sun Y; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, V6T1Z3, BC, Canada.
  • Schipper MJ; Divisions of Neurology and Hematology and Oncology, Children's and Women's Health Centre of B.C, University of British Columbia, Vancouver, BC, V6H 3N1, Canada.
  • Chavez L; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
  • Margol A; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
  • Pekmezci M; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Chung C; Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine University of Southern California, Los Angeles, CA, 90027, USA.
  • Banda A; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
  • Bayliss JM; Department of Pathology, University of Michigan, Ann Arbor, MI, 48104, USA.
  • Curry SJ; Department of Pathology, University of Michigan, Ann Arbor, MI, 48104, USA.
  • Santi M; Department of Pathology, University of Michigan, Ann Arbor, MI, 48104, USA.
  • Rodriguez FJ; Division of Haematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
  • Snuderl M; Department of Anatomic Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
  • Karajannis MA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Saratsis AM; Department of Pathology, New York University, New York, NY, USA.
  • Horbinski CM; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
  • Carret AS; Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
  • Wilson B; Division of Pediatric Neurosurgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, 60611, USA.
  • Johnston D; Department of Pathology and Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
  • Lafay-Cousin L; Division of Hematology-Oncology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, QC, Canada.
  • Zelcer S; Division of Pediatric Hematology/Oncology, Stollery Children's Hospital, University of Alberta, Edmonton, AB, T2W3N2, Canada.
  • Eisenstat D; Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada.
  • Silva M; Division of Pediatric Hematology/Oncology, Alberta Children's Hospital, Calgary, AB, T3B6A8, Canada.
  • Scheinemann K; Division of Pediatric Hematology/Oncology, London Health Sciences Center, Children's Hospital, London, ON, N6A5A5, Canada.
  • Jabado N; Department of Pediatrics and Medical Genetics, University of Alberta, Edmonton, AB, Canada.
  • McNeely PD; Kingston General Hospital, Kingston, ON, Canada.
  • Kool M; Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
  • Pfister SM; Division of Hematology/Oncology, University Children Hospital of Basel (UKBB) and University of Basel, Basel, Switzerland.
  • Taylor MD; Department of Pediatrics, McGill University, Montreal, QC, H3Z2Z3, Canada.
  • Hawkins C; Department of Human Genetics, McGill University, Montreal, QC, H3Z2Z3, Canada.
  • Korshunov A; Division of Neonatal Pediatrics, Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
  • Judkins AR; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Venneti S; German Cancer Consortium (DKTK), Heidelberg, Germany.
Acta Neuropathol ; 134(5): 705-714, 2017 11.
Article en En | MEDLINE | ID: mdl-28733933
Posterior fossa ependymomas (EPN_PF) in children comprise two morphologically identical, but biologically distinct tumor entities. Group-A (EPN_PFA) tumors have a poor prognosis and require intensive therapy. In contrast, group-B tumors (EPN_PFB) exhibit excellent prognosis and the current consensus opinion recommends future clinical trials to test the possibility of treatment de-escalation in these patients. Therefore, distinguishing these two tumor subtypes is critical. EPN_PFA and EPN_PFB can be distinguished based on DNA methylation signatures, but these assays are not routinely available. We have previously shown that a subset of poorly prognostic childhood EPN_PF exhibits global reduction in H3K27me3. Therefore, we set out to determine whether a simple immunohistochemical assay for H3K27me3 could be used to segregate EPN_PFA from EPN_PFB tumors. We assembled a cohort of 230 childhood ependymomas and H3K27me3 immunohistochemistry was assessed as positive or negative in a blinded manner. H3K27me3 staining results were compared with DNA methylation-based subgroup information available in 112 samples [EPN_PFA (n = 72) and EPN_PFB tumors (n = 40)]. H3K27me3 staining was globally reduced in EPN_PFA tumors and immunohistochemistry showed 99% sensitivity and 100% specificity in segregating EPN_PFA from EPN_PFB tumors. Moreover, H3K27me3 immunostaining was sufficient to delineate patients with worse prognosis in two independent, non-overlapping cohorts (n = 133 and n = 97). In conclusion, immunohistochemical evaluation of H3K27me3 global reduction is an economic, easily available and readily adaptable method for defining high-risk EPN_PFA from low-risk posterior fossa EPN_PFB tumors to inform prognosis and to enable the design of future clinical trials.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Infratentoriales / Ependimoma / Histona Demetilasas con Dominio de Jumonji Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Año: 2017 Tipo del documento: Article
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Infratentoriales / Ependimoma / Histona Demetilasas con Dominio de Jumonji Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Año: 2017 Tipo del documento: Article