Abstract
Since the spread of tumor cells to the bone marrow (BM) is a grim prognostic indicator for patients with neuroblastoma (NB), the search for BM infiltration is of utmost importance for both staging and therapeutic purposes. According to the International Neuroblastoma Staging System, presence of metastases in BM is assessed by morphological examination of BM smears and trephine biopsies. In spite of the limited sensitivity of morphological analysis, alternative modalities for NB detection has not been incorporated into the staging system because patients with localized NB are not supposed to have clinically relevant circulating tumor cells, as demonstrated by their good survival rate. Some of these patients, however, relapse and may die of the disease. We thus evaluated the prognostic role of more sensitive methods, i.e., immunocytology (IC) and molecular analysis (qualitative and quantitative RT-PCR) in large cohorts of patients with localized NB. Although IC and RT-PCR displayed similar sensitivity and specificity in simulated samples, anti GD2 IC demonstrated to have a prognostic role, independent from other known risk factors. Thus, GD2-IC represents an independent, quantitative and easy to perform tool that may contribute to individuate children at risk of relapse that may benefit of a closer follow-up. Conversely, RT-qPCR seems to have limited value in children with localized NB, even if TH RT-qPCR, performed in peripheral blood samples, demonstrated to have a prognostic role. A high percentage of samples, in fact, tested positive for several markers without correlation with clinical events, with the exception of Phox2b that was mostly negative. Thus, efficacy of multiple target molecular monitoring in overcoming tumor heterogeneity is questioned, and we believe that only TH and Phox2b RT-qPCRs deserve future studies in children with localized NB.
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Acknowledgements
These studies were supported in part by Italian Neuroblastoma Foundation and Italian Ministry of Health. The excellent technical support of Mrs B. Carlini is deeply acknowledged. Images of smear, trephine biopsy and anti-GD2 IC were kindly provided by Drs F. Scuderi, C. Gambini and A.R. Sementa, respectively.
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Corrias, M.V. (2012). Role of Bone Marrow Infiltration Detected by Sensitive Methods in Patients with Localized Neuroblastoma. In: Hayat, M. (eds) Neuroblastoma. Pediatric Cancer, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2418-1_24
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