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Loss in Chromosome 11q Identifies Tumors with Increased Risk for Metastatic Relapses in Localized and 4S Neuroblastoma

Authors' Affiliations: ¹ Department of Pediatric Oncology, University Children's Hospital, Köln, Germany and ² Center for Molecular Medicine Cologne, Cologne, Germany

Requests for reprints: Ruediger Spitz, Department of Pediatric Oncology and Hematology, University Children's Hospital, Kerpener-Str. 62, 50924 Köln, Germany. Phone: 49-221-478-6816; Fax: 49-221-478-4689; E-mail: Ruediger.Spitz{at}uk-koeln.de.

Purpose: To improve risk prediction in neuroblastoma and to specify the type of a possible relapse, alterations in the long arm of chromosome 11 were analyzed.

Experimental Design: A representative cohort of 611 neuroblastomas was investigated for deletion events in distal chromosome 11q using interphase fluorescence in situ hybridization.

Results: Alterations in 11q were found in 159 of 611 tumors in the whole cohort (26%) and were associated with stage 4 disease (P < 0.001) and age at diagnosis of >2.5 years (P < 0.001). Event-free survival and overall survival were significantly poorer for patients with 11q loss in the whole cohort (event-free survival and overall survival, P < 0.001) and in different subsets: neuroblastoma without MYCN amplification (MNA) (event-free survival and overall survival, P < 0.001), with MNA (event-free survival, P = 0.03; overall survival, P = 0.02), and MYCN-nonamplified stage 1, 2, 3, and 4S tumors with and without del 1p (event-free survival and overall survival, P < 0.001). In stage 4, the 11q status did not discriminate outcome. By multivariate analysis, the 11q status proved prognostic for event-free survival in the whole cohort (P = 0.008; hazard ratio, 1.573) and in the subgroup of stages 1, 2, 3, and 4S without MNA (P < 0.001; hazard ratio, 3.534). Moreover, 11q alterations were strongly correlated with the occurrence of metastatic relapses (P < 0.001).

Conclusion: In addition to the current risk stratification, the status of 11q enables the identification of patients with an increased risk for relapses in general and metastatic relapses in particular.

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