Affiliations: Laboratory of Oncology, Gaslini Institute, Genoa, Italy | Service of Pathology, Gaslini Institute, Genoa, Italy | Immunotherapy Unit, Department of Translational Oncology, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy | Department of Medicinal Chemistry, University of Pisa, Pisa, Italy
Note: [] Corresponding author: Silvano Ferrini, Immunotherapy Unit, Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132 Genoa, Italy. Tel.: +39 010 5737372; Fax: +39 010 5737374; E-mail: [email protected].
Abstract: Background: The Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166), 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. Conclusion: 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.
