The analysis of CD44 cell-surface expression must be recommended as an additional biologic marker in the initial staging of the disease.

Intensified chemotherapy using CADO/CVP increases CR rates despite a shorter induction duration. However, the rate of MIBG normalization remains unsatisfactory and could be raised through the dose-intensive use of agents such as cyclophosphamide.

No abstract

The purpose of this work was to compare technetium-99m-diphosphono-propanedicarboxylate (DPD) and iodine-123-metaiodobenzylguanidine (MIBG) scans in the diagnosis and follow-up of neuroblastoma, and to study the role of histological differentiation in the uptake of MIBG. The uptake of MIBG and of DPD were studied retrospectively in 27 patients with neuroblastoma (primary, residual and recurrent tumours as well as bone and bone marrow metastases). The findings were related to the histological classification of the tumours as neuroblastoma (N1), differentiating neuroblastoma (N2) or ganglioneuroblastoma (N3). Uptake of MIBG by the primary tumour occurred in 17 of 19 patients, either at diagnosis or during follow-up. There were only two false-negatives with MIBG, both of which were N3. Ten patients were studied preoperatively with both MIBG and DPD. The primary tumour showed MIBG uptake in nine of the ten and DPD uptake in eight of them. Thirty-five sites of cortical bone metastasis were shown in eight patients by both MIBG and DPD, 12 sites in seven patients by MIBG only and seven sites in five patients by DPD only. In 14 patients both MIBG and bone scan were negative. Overall, MIBG demonstrated more lesions than DPD. Retrospectively several hot spots seen only with the bone scan are to be considered as false-positive. The highest incidence of false-negative MIBG and bone scans was observed in ganglioneuroblastoma with a predominance of the more mature component (ganglioneuroma).

Testing with a panel of 26 monoclonal antibodies (MAbs) showed the antigenic profile of 13 human neuroblastoma cell lines to be characterized by a generally poor antigenic expression; therefore, Interferon-gamma (IFN-gamma), dibutyryl cyclic-AMP and retinoic acid were used to analyse the modulation of surface antigenic expression during differentiation. Treatment of neuroblastoma cell lines with IFN-gamma resulted mainly in induction or increase of class-I MHC antigenic expression. Induction of class-II MHC antigens was obtained on only one neuroblastoma cell line out of 13, thus representing an exceptional event. An increase in some other antigens expressed by neuroblastoma cell lines was also observed. In contrast, and in addition to morphological maturation, treatment of these cell lines with the differentiation inducer dibutyryl-cyclic-AMP (dbc-AMP), resulted in general down-modulation of antigenic expression, particularly of neuroblastoma-associated 5A7 or Leu7 antigens. Retinoic acid treatment had no significant effect on MHC antigens, but it decreased expression of 5A7 and Leu7 antigens, and markedly increased the expression of the melanoma-associated antigen Me14-D12. The similarity between the antigenic profile of in vitro differentiated neuroblastoma cells and that of mature ganglioneuroma cells suggests that compounds like cyclic-AMP or retinoic acid are excellent tools for further investigations of the mechanisms of neuroblastoma differentiation and might have important clinical applications.