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Cellular Oncology
Volume 32, Issue 1-2, Pages 77-86
http://dx.doi.org/10.3233/CLO-2009-0494

Different Subcellular Localization of ALCAM Molecules in Neuroblastoma: Association with Relapse

Maria Valeria Corrias,1 Claudio Gambini,2 Andrea Gregorio,2 Michela Croce,3 Gaia Barisione,3 Claudia Cossu,3 Armando Rossello,4 Silvano Ferrini,3 and Marina Fabbi3

1Laboratory of Oncology, Gaslini Institute, Genoa, Italy
2Service of Pathology, Gaslini Institute, Genoa, Italy
3Immunotherapy Unit, Department of Translational Oncology, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
4Department of Medicinal Chemistry, University of Pisa, Pisa, Italy

Copyright © 2010 Hindawi Publishing Corporation and the authors. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: The Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD), involved in nervous system development, has been linked to tumor progression and metastasis in several tumors. No information is available on ALCAM expression in neuroblastoma, a childhood neoplasia originating from the sympathetic nervous system.

Methods: ALCAM expression was analysed by immunofluorescence and immunohistochemistry on differentiated neuroblastoma cell lines and on archival specimens of stroma-poor, not MYCN amplified, resectable neuroblastoma tumors, respectively.

Results: ALCAM is variously expressed in neuroblastoma cell lines, is shed by metalloproteases and is cleaved by ADAM17/TACE in vitro. ALCAM is expressed in neuroblastoma primary tumors with diverse patterns of subcellular localization and is highly expressed in the neuropil area in a subgroup of cases. Tumor specimens showing high expression of ALCAM at the membrane of the neuroblast body or low levels in the neuropil area are associated with relapse (P = 0.044 and P < 0.0001, respectively). In vitro differentiated neuroblastoma cells show strong ALCAM expression on neurites, suggesting that ALCAM expression in the neuropil is related to a differentiated phenotype.

Conclusions: Assessment of ALCAM localization by immunohistochemistry may help to identify patients who, in the absence of negative prognostic factors, are at risk of relapse and require a more careful follow-up.