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Serum levels of cytoplasmic melanoma-associated antigen at diagnosis may predict clinical relapse in neuroblastoma patients

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Abstract

The high molecular weight melanoma-associated antigen (HMW-MAA) and the cytoplasmic melanoma-associated antigen (cyt-MAA/LGALS3BP) are expressed in melanoma. Their serum levels are increased in melanoma patients and correlate with clinical outcome. We investigated whether these molecules can serve as prognostic markers for neuroblastoma (NB) patients. Expression of cyt-MAA and HMW-MAA was evaluated by flow cytometry in NB cell lines, patients’ neuroblasts (FI-NB), and short-term cultures of these latter cells (cNB). LGALS3BP gene expression was evaluated by RT–qPCR on FI-NB, cNB, and primary tumor specimens. Soluble HMW-MAA and cyt-MAA were tested by ELISA. Cyt-MAA and HMW-MAA were expressed in NB cell lines, cNB, and FI-NB samples. LGALS3BP gene expression was higher in primary tumors and cNB than in FI-NB samples. Soluble cyt-MAA, but not HMW-MAA, was detected in NB cell lines and cNBs supernatants. NB patients’ serum levels of both antigens were higher than those of the healthy children. High cyt-MAA serum levels at diagnosis associated with higher incidence of relapse, independently from other known risk factors. In conclusion, both HMW-MAA and cyt-MAA antigens, and LGALS3BP gene, were expressed by NB cell lines and patients’ neuroblasts, and both antigens’ serum levels were increased in NB patients. Elevated serum levels of cyt-MAA at diagnosis correlated with relapse, supporting that cyt-MAA may serve as early serological biomarker to individuate patients at higher risk of relapse that may require a more careful follow-up, after being validated in a larger cohort of patients at different time-points during follow-up. Given its immunogenicity, cyt-MAA may also be a potential target for NB immunotherapy.

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Acknowledgments

This work has been supported by grants from Ministero della Salute, Progetti di Ricerca Corrente. BC is recipient of a Fondazione Italiana per la Lotta al Neuroblastoma fellowship. SS is recipient of a fellowship from Ministero della Salute/Regione Liguria. We thank Mrs Chiara Bernardini and Camilla Valentino for excellent secretarial assistance, Dr. Mirco Ponzoni, Genoa, for providing us the G2a anti-GD2 antibody and Mrs Barbara Galleni at the Italian NB registry, Genoa, for the excellent work aimed at providing clinical data on NB patients.

Conflict of interest

The authors disclose any conflict of interest.

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Authors and Affiliations

  1. Laboratory of Oncology, G. Gaslini Children’s Hospital, Largo G. Gaslini 5, 16148, Genoa, Italy

    Fabio Morandi, Maria Valeria Corrias, Lizzia Raffaghello, Barbara Carlini, Paola Bocca, Ignazia Prigione & Vito Pistoia

  2. Clinical Pathology, G. Gaslini Children’s Hospital, Genoa, Italy

    Isabella Levreri

  3. Centro Fisiopatologia della Riproduzione Umana, UO Ostetricia e Ginecologia, Azienda Ospedaliera Universitaria “San Martino”, Genoa, Italy

    Paola Scaruffi

  4. Translational Oncopathology, National Cancer Research Institute (IST), Genoa, Italy

    Sara Stigliani

  5. Department of Hematology-Oncology, G. Gaslini Children’s Hospital, Genoa, Italy

    Loredana Amoroso

  6. Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    Soldano Ferrone

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  1. Fabio Morandi
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Correspondence to Fabio Morandi.

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Morandi, F., Corrias, M.V., Levreri, I. et al. Serum levels of cytoplasmic melanoma-associated antigen at diagnosis may predict clinical relapse in neuroblastoma patients. Cancer Immunol Immunother 60, 1485–1495 (2011). https://doi.org/10.1007/s00262-011-1052-0

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