title: Augmented expression of MYC and/or MYCN protein defines highly aggressive MYC-driven neuroblastoma: a Children's Oncology Group study.
abstract: BACKGROUND
  MYCN amplification with subsequent MYCN protein overexpression is a powerful indicator of poor prognosis of neuroblastoma patients. Little is known regarding the prognostic significance of the homologous MYC protein expression in neuroblastoma.
  
  
  METHODS
  Immunostaining for MYCN and MYC protein was performed on 357 undifferentiated/poorly differentiated neuroblastomas. Results were analysed with other prognostic markers.
  
  
  RESULTS
  Sixty-seven (19%) tumours were MYCN(+), 38 (11%) were MYC(+), and one(0.3%) had both proteins(+). MYCN(+) tumours and MYC(+) tumours were more likely diagnosed in children>18months with stage4-disease. MYCN(+) tumours were associated with amplified MYCN, Unfavourable Histology (UH), and High-MKI (Mitosis-Karyorrhexis Index). MYC(+) tumours were also frequently UH but not associated with MYCN amplification, and more likely to have low-/intermediate-MKI. Favourable Histology patients without MYC/MYCN expressions exhibited the best survival (N=167, 89.7±5.5% 3-year EFS, 97.0±3.2% 3-year OS), followed by UH patients without MYC/MYCN expressions (N=84, 63.1±13.6% 3-year EFS, 83.5±9.4% 3-year OS). MYCN(+)patients and MYC(+)patients had similar and significantly low (P<0.0001) survivals (46.2±12.0% 3-year EFS, 63.2±12.1% 3-year OS and 43.4±23.1% 3-year EFS, 63.5±19.2% 3-year OS, respectively). Notably, the prognostic impact imparted by MYC expression was independent from other markers.
  
  
  CONCLUSIONS
  In this series, ∼30% of neuroblastomas had augmented MYCN or MYC expression with dismal survivals. Prospective study of MYC/MYCN protein expression signature as a new biomarker for high-risk neuroblastomas should be conducted.
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA.
authors.forename: R
authors.initials: R
authors.lastname: Teshiba
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: N
authors.initials: N
authors.lastname: Ikegaki
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: X X
authors.initials: XX
authors.lastname: Tang
authors.affiliation: Department of Biostatistics, Children's Oncology Group Statistics and Data Center, University of Florida, Gainesville, FL 32607, USA.
authors.forename: A
authors.initials: A
authors.lastname: Naranjo
authors.affiliation: Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: W B
authors.initials: WB
authors.lastname: London
authors.affiliation: Division of Oncology and Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Hogarty
authors.affiliation: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital and Departments of Pathology and Pediatrics, Ohio State University College of Medicine, Columbus, OH 43210, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Gastier-Foster
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Look
authors.affiliation: Department of Pediatrics, Seattle Children's Hospital, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, Seattle, WA 98105, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Park
authors.affiliation: Division of Oncology and Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Maris
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Cohn
authors.affiliation: Division of Hematology/Oncology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Seeger
authors.affiliation: Division of Hematology/Oncology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA.
authors.forename: S
authors.initials: S
authors.lastname: Asgharzadeh
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA.
authors.forename: H
authors.initials: H
authors.lastname: Shimada
mesh_terms: D002454:Cell Differentiation; D002648:Child; D015331:Cohort Studies; D016259:Genes, myc; D006801:Humans; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D011379:Prognosis
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins