Navin Pinto1, Jodi R Mayfield2, Gordana Raca3, Mark A Applebaum4, Alexandre Chlenski4, Madina Sukhanova5, Rochelle Bagatell6, Meredith S Irwin7, Anthony Little6, Jawhar Rawwas8, Yasmin Gosiengfiao9, Olivier Delattre10, Isabelle Janoueix-Lerosey10, Eve Lapouble11, Gudrun Schleiermacher10,11,12, Susan L Cohn3. 1. Division of Pediatric Hematology/Oncology, Seattle Children's Hospital, Seattle, Washington. 2. Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico. 3. Department of Pediatrics, University of Chicago, Chicago, Illinois. 4. Department of Pediatrics, University of Southern California, Los Angeles, California. 5. Department of Medicine, University of Chicago, Chicago, Illinois. 6. Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 7. Department of Pediatrics, Hospital for Sick Children (Toronto), Toronto, Ontario, Canada. 8. Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota. 9. Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois. 10. Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France. 11. Unité de Génétique Somatique, Institut Curie, Paris, France. 12. Département de Pédiatrie, Institut Curie, Paris, France.
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.
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 neuroblastomapatients, and multiple SCAs may be predictive of metastatic relapse.
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