Abstract 875 Poster Session II, Sunday, 5/2 (poster 144)

Metastatic neuroblastoma (NB) in children less than 1 year of age generally has better prognosis. However, the two different types of dissemination (stage 4 and stage 4s) have completely different biology. Stage 4s is characterized by spontaneous remission whereas stage 4 requires systemic therapy for cure. Clinical classification of these two tumor categories can be difficult and no uniform and consistent biological or genetic markers have been identified that reliably distinguish the two. From 1987 to 1998, patients (8 stage 4s, 11 stage 4) at Memorial Sloan-Kettering Cancer Center were staged according to the International Neuroblastoma Staging System. Twenty-five tumor samples were obtained for LOH analysis at 15 highly informative, polymorphic PCR markers mapping to chromosome 1 using a sensitive, semiautomated, fluorescent detection system. Distinct patterns of LOH correlated with individual clinical stages (see table). Stage 4 tumors (regardless of age) were predominately diploid with extensive LOH frequently detected in the region of 1ptel to 1p35 and at 1p31 to 1p22. Stage 4s tumors were mostly aneuploid without deletion of 1p36 or 1p22 however LOH was detected at 1p31. All 8 stage 4s patients (metastases to liver 8/8, to marrow 4/8, distant nodes 3/8, skin 3/8) underwent spontaneous remission (5/8 following recurrence) of gross disease without cytotoxic therapy. In contrast, only 73% of infant stage 4 patients survived despite combined modality therapy. These findings suggest that genes located at distinct regions of 1p play a significant role in the biology of neuroblastoma and LOH analysis can help define the 4s stage in order to spare young children the acute and long term side effects of therapy.

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