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BioMed Research International
Volume 2015, Article ID 347867, 10 pages
Research Article

Expression of FOXP3, CD14, and ARG1 in Neuroblastoma Tumor Tissue from High-Risk Patients Predicts Event-Free and Overall Survival

1Physiopathology of Human Reproduction, IRCCS A.O.U. San Martino-IST, 16132 Genoa, Italy
2Laboratory of Biotherapy, IRCCS A.O.U. San Martino-IST, 16132 Genoa, Italy
3Laboratory of Oncology, IRCCS Istituto Giannina Gaslini, 16148 Genoa, Italy
4Oncology Unit, IRCCS Istituto Giannina Gaslini, 16148 Genoa, Italy
5Epidemiology, Biostatistics and Committees Unit, IRCCS Istituto Giannina Gaslini, 16148 Genoa, Italy
6Neuroblastoma Laboratory, Pediatric Research Institute, Fondazione Città della Speranza, 35127 Padua, Italy

Received 10 July 2014; Revised 12 January 2015; Accepted 14 January 2015

Academic Editor: Mohammad Owais

Copyright © 2015 Sara Stigliani et al. 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.


The prognosis of children with metastatic neuroblastoma (NB) > 18 months at diagnosis is dismal. Since the immune status of the tumor microenvironment could play a role in the history of disease, we evaluated the expression of CD45, CD14, ARG1, CD163, CD4, FOXP3, Perforin-1 (PRF1), Granzyme B (GRMB), and IL-10 mRNAs in primary tumors at diagnosis from children with metastatic NB and tested whether the transcript levels are significantly associated to event-free and overall survival (EFS and OS, resp.). Children with high expression of CD14, ARG1 and FOXP3 mRNA in their primary tumors had significantly better EFS. Elevated expression of CD14, and FOXP3 mRNA was significantly associated to better OS. CD14 mRNA expression levels significantly correlated to all markers, with the exception of CD4. Strong positive correlations were found between PRF1 and CD163, as well as between PFR1 and FOXP3. It is worth noting that the combination of high levels of CD14, FOXP3, and ARG1 mRNAs identified a small group of patients with excellent EFS and OS, whereas low levels of CD14 were sufficient to identify patients with dismal survival. Thus, the immune status of the primary tumors of high-risk NB patients may influence the natural history of this pediatric cancer.