title: Segmental Chromosomal Aberrations in Localized Neuroblastoma Can be Detected in Formalin-Fixed Paraffin-Embedded Tissue Samples and Are Associated With Recurrence.
abstract: BACKGROUND
  Array comparative genomic hybridization (CGH) analyses of frozen tumors have shown strong associations between the pattern of chromosomal aberrations and outcome in patients with advanced-stage neuroblastoma. New platforms for analyzing chromosomal aberrations using formalin-fixed paraffin-embedded (FFPE) tissue have recently been developed. We sought to determine whether chromosomal microarray analysis (CMA) using FFPE tumors is feasible and if segmental chromosomal aberrations were prognostic of recurrence in localized neuroblastoma.
  
  
  METHODS
  Patients with MYCN nonamplified International Neuroblastoma Staging System stage 1 and 2 disease who recurred were identified. CMA was performed with diagnostic FFPE samples using OncoScan™ FFPE Express 2.0. The prognostic significance of chromosomal pattern was validated in 105 patients with available CGH results.
  
  
  RESULTS
  In 26 evaluable patients, 11 recurred locally, nine had metastatic relapse, and six remained progression free >3 years from diagnosis. No chromosomal aberrations were identified in four tumors. Numerical chromosomal aberrations (NCAs) without segmental chromosomal aberration (SCA) were identified in 11 patients: six progressed locally, two had metastatic progression and 3 remained progression-free. Eleven patients had SCAs: four progressed locally, six developed metastatic progression and one remained progression-free. Five or more SCAs were only detected in tumors from patients who developed metastases (P = 0.0004). In the validation cohort, SCAs were associated with inferior event-free survival (EFS) compared to NCA (5-year EFS 68% ± 8.3% vs. 91% ± 3.6%, respectively; P = 0.0083).
  
  
  CONCLUSIONS
  It is feasible to evaluate chromosomal aberrations using FFPE neuroblastoma tissue. SCA is associated with inferior EFS in localized neuroblastoma patients, and multiple SCAs may be predictive of metastatic relapse.
authors: Division of Pediatric Hematology/Oncology, Seattle Children's Hospital, Seattle, Washington.
authors: Navin
authors: N
authors: Pinto
authors: Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico.
authors: Jodi R
authors: JR
authors: Mayfield
authors: Department of Pediatrics, University of Chicago, Chicago, Illinois.
authors: Gordana
authors: G
authors: Raca
authors: Department of Pediatrics, University of Southern California, Los Angeles, California.
authors: Mark A
authors: MA
authors: Applebaum
authors: Department of Pediatrics, University of Southern California, Los Angeles, California.
authors: Alexandre
authors: A
authors: Chlenski
authors: Department of Medicine, University of Chicago, Chicago, Illinois.
authors: Madina
authors: M
authors: Sukhanova
authors: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors: Rochelle
authors: R
authors: Bagatell
authors: Department of Pediatrics, Hospital for Sick Children (Toronto), Toronto, Ontario, Canada.
authors: Meredith S
authors: MS
authors: Irwin
authors: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors: Anthony
authors: A
authors: Little
authors: Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota.
authors: Jawhar
authors: J
authors: Rawwas
authors: Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
authors: Yasmin
authors: Y
authors: Gosiengfiao
authors: Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France.
authors: Olivier
authors: O
authors: Delattre
authors: Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France.
authors: Isabelle
authors: I
authors: Janoueix-Lerosey
authors: Unité de Génétique Somatique, Institut Curie, Paris, France.
authors: Eve
authors: E
authors: Lapouble
authors: Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France.|Unité de Génétique Somatique, Institut Curie, Paris, France.|Département de Pédiatrie, Institut Curie, Paris, France.
authors: Gudrun
authors: G
authors: Schleiermacher
authors: Department of Pediatrics, University of Chicago, Chicago, Illinois.
authors: Susan L
authors: SL
authors: Cohn
mesh_terms: D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D018572:Disease-Free Survival; D005260:Female; D005557:Formaldehyde; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016612:Paraffin Embedding; D016707:Tissue Fixation
chemical_list: D005557:Formaldehyde
keywords: low-risk neuroblastoma; metastatic relapse; segmental chromosomal aberrations