Prognostic significance of GAGE detection in bone marrows on survival of patients with metastatic neuroblastoma.
BACKGROUND
Previously, we reported the utility of GAGE as a molecular marker for neuroblastoma (NB) and malignant melanoma in blood and bone marrow (BM). Among patients with stage III melanoma rendered disease-free by surgery, GAGE expression was a strong prognostic factor for patient survival.


METHODS
All patients with advanced NB diagnosed at > 1 year of age initially treated with protocol N6 (n = 24) and N7 (n = 38) at Memorial Sloan-Kettering Cancer Center were included in this study. Their BM cells at 12, 18, and 24 months (median time after diagnosis) were evaluated for the presence of GAGE.


RESULTS
GAGE positivity at 12 months (25%), when patients were still on treatment, did not predict progression-free survival (PFS) and overall survival from the time of sampling. Positivity at 18 months (29%) was associated with poorer PFS and survival (but P > 0.05). By 24 months, the presence of GAGE (26%) was a very strong predictor of out-come (P < 0.001). When only remission marrows at 24 months were analyzed, PFS was 4.7-fold lower among GAGE-positive patients. Thirty-seven percent of N6 patients were positive for GAGE, in contrast to 17% of the patients in the more current regimen N7.


CONCLUSIONS
The detection of GAGE by RT-PCR in marrow may have utility in molecular staging of patients in clinical remission. It may allow earlier identification of patients at risk, such that appropriate intervention can be given before clinical relapse. GAGE may also serve as a surrogate endpoint for adjuvant treatment strategies, and to determine the duration of therapy.
Cheung
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Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. cheungi@mskcc.org
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Cheung
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D000951:Antigens, Neoplasm / Q000235:genetics*; D001853:Bone Marrow / Q000737:chemistry*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D018365:Neoplasm, Residual; D009447:Neuroblastoma / Q000401:mortality* / Q000556:secondary*; D011379:Prognosis; D015996:Survival Rate; D013997:Time Factors
D000951:Antigens, Neoplasm