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Expression of Inhibitor-of-Apoptosis Protein (IAP) Livin by Neuroblastoma Cells: Correlation with Prognostic Factors and Outcome

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Pediatric and Developmental Pathology

Abstract

Livin is a recently identified member of the Inhibitor-of-Apoptosis protein (IAP) family of antiapoptosis proteins, and expression has been reported in melanoma and some types of carcinoma. We evaluated livin expression in paraffin-embedded tumor tissue from 68 patients with neuroblastoma (NB) and 7 NB cell lines by immunoperoxidase using an anti-livin monoclonal antibody. Eighteen (26.5%) of the 68 NB tumor tissues showed high livin expression, 36 (53%) showed low-intermediate expression, and 14 (20.5%) were negative. Similarly, 4 NB cell lines showed high livin expression, and 3 showed intermediate expression. In primary NB tissue, livin was observed mainly in tumor neuropil, an extension of tumor cell cytoplasm, and the cytoplasm itself. By reverse transcriptase–polymerase chain reaction, livin expression was confirmed in all 7 NB lines and in frozen tissue from 1 of 3 primary tumors examined to date, in agreement with immunohistochemical data; both livin α and β isoforms were detected. In the NB cases, we further analyzed the correlation between livin expression and clinical and biological features with established prognostic significance (i.e., age at diagnosis, stage, histology, and MYCN oncogene status), and patients’ outcome. Livin expression alone did not appear to have an effect on survival; however, patients with high livin expression and amplified MYCN had significantly decreased survival compared with patients lacking both markers or with either of these markers alone. These results suggest that (a) livin is expressed in primary and cultured neuroblastoma cells and (b) high livin expression may identify a subset of neuroblastoma patients with a particularly poor prognosis among those with MYCN amplified tumors.

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Acknowledgments

This study was supported by a grant from CURE Childhood Cancer, Inc. We thank Dr. Nao Ikegaki (Emory University) for critical reading of this manuscript.

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Authors and Affiliations

  1. Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, 30322, USA

    Dae-Kwang Kim, Carlos S. Alvarado, Lubing Gu, Muxiang Zhou & Harry W. Findley

  2. Department of Pathology, Emory University School of Medicine, Atlanta, Georgia, 30322, USA

    Carlos R. Abramowsky

  3. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, 30322, USA

    Minn-Minn Soe & Kevin Sullivan

  4. Division of Hematology/Oncology, Children’s Healthcare of Atlanta at Scottish Rite, Atlanta, Georgia, 30342, USA

    Bradley George

  5. Department of Pathology, Children’s Healthcare of Atlanta at Scottish Rite, Atlanta, Georgia, 30342, USA

    Erwin Schemankewitz

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  1. Dae-Kwang Kim
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  2. Carlos S. Alvarado
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  3. Carlos R. Abramowsky
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  4. Lubing Gu
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  5. Muxiang Zhou
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  6. Minn-Minn Soe
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  7. Kevin Sullivan
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  8. Bradley George
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  9. Erwin Schemankewitz
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  10. Harry W. Findley
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Corresponding authors

Correspondence to Carlos S. Alvarado or Harry W. Findley.

Additional information

Harry W. Findley and Carlos S. Alvarado contributed equally to this study.

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Kim, DK., Alvarado, C.S., Abramowsky, C.R. et al. Expression of Inhibitor-of-Apoptosis Protein (IAP) Livin by Neuroblastoma Cells: Correlation with Prognostic Factors and Outcome. Pediatr Dev Pathol 8, 621–629 (2005). https://doi.org/10.1007/s10024-005-4108-3

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  • DOI: https://doi.org/10.1007/s10024-005-4108-3

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