Research Article Soluble HLA-G and HLA-E Levels in Bone Marrow Plasma Samples Are Related to Disease Stage in Neuroblastoma Patients Fabio Morandi, 1 Sarah Pozzi, 2 Barbara Carlini, 1 Loredana Amoroso, 3 Vito Pistoia, 1 and Maria Valeria Corrias 1 1 Laboratorio di Oncologia, Istituto Giannina Gaslini, Via Gaslini 5, 16147 Genoa, Italy 2 Centro Cellule Staminali, IRCCS AOU San Martino-IST, Largo R. Benzi 10, 16132 Genoa, Italy 3 UOC Oncologia, Istituto Giannina Gaslini, Via Gaslini 5, 16147 Genoa, Italy Correspondence should be addressed to Fabio Morandi; fabiomorandi@gaslini.org Received 20 May 2016; Revised 4 July 2016; Accepted 19 July 2016 Academic Editor: Ban-Hock Toh Copyright © 2016 Fabio Morandi et al. is 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. e role of nonclassical HLA-class Ib molecules HLA-G and HLA-E in the progression of Neuroblastoma (NB), the most common pediatric extracranial solid tumor, has been characterized in the last years. Since BM infiltration by NB cells is an adverse prognostic factor, we have here analyzed for the first time the concentration of soluble (s)HLA-G and HLA-E in bone marrow (BM) plasma samples from NB patients at diagnosis and healthy donors. sHLA-G and sHLA-E are present in BM plasma samples, and their levels were similar between NB patients and controls, thus suggesting that these molecules are physiologically released by resident or stromal BM cell populations. is hypothesis was supported by the finding that sHLA-G and sHLA-E levels did not correlate with BM infiltration and other adverse prognostic factors (MYCN amplification and age at diagnosis). In contrast, BM plasma levels of both molecules were higher in patients with metastatic disease than in patients with localized NB, thus suggesting that concentration of these molecules might be correlated with disease progression. e prognostic role of sHLA-G and sHLA-E concentration in the BM plasma for NB patients will be evaluated in future studies, by analyzing the clinical outcome of the same NB patients at follow- up. 1. Introduction Neuroblastoma (NB) is the most common extracranial solid tumor in children, with an incidence of 1 case per 100.000 children per year, and causes 15% of cancer deaths in pediatric age. NB originates from the sympathetic nervous system, most frequently in the adrenal medulla or the paraspinal ganglia. e causes are unknown, although 1-2% of NB may have a hereditary basis. Different genetic alterations have been characterized in NB, that is, gain-of-function of ALK gene, losses of 11q and 1p, gain of 17q, and amplification of the MYCN gene. NB is heterogeneous, as it may undergo spontaneous remission or evolve to progressive metastatic disease, with dissemination to lymph nodes, bone, bone marrow, liver, skin, and other organs [1]. In particular, BM infiltration is an indicator of poor outcome for NB patients [2]. e International Neuroblastoma Risk Group staging system takes into account genetic alterations, DNA ploidy, histological features, and clinical data, as criteria for defining the risk classes. e prognosis of low/intermediate risk NB patients is favorable, and tumors can be cured by surgery alone or minimal chemotherapy. In contrast, high- risk NB patients’ prognosis is poor, in spite of aggressive treatment based on surgery, chemotherapy, radiation therapy, hematopoietic stem cell transplantation, and adjuvant ther- apy with retinoic acid. In fact, survival rates of these patients at 5 years are less than 50% [3]. In the last years, the role of HLA-class Ib molecules in the progression of NB has been characterized by our group [4– 7] and by others [8]. HLA-Ib family includes HLA-G, HLA- E, HLA-F, and HLA-H. In contrast with high polymorphic HLA-Ia molecules (HLA-A, HLA-B, and HLA-C) all these molecules display a limited polymorphism, with few alleles encoding a limited number of functional proteins. Moreover, although HLA-class Ib molecules can bind small peptides and present them to specific CD8 + T cell subsets (similarly Hindawi Publishing Corporation Journal of Immunology Research Volume 2016, Article ID 7465741, 6 pages http://dx.doi.org/10.1155/2016/7465741