Loss of heterozygosity at 1p36 independently predicts for disease progression but not decreased overall survival probability in neuroblastoma patients: A Children's Cancer Group study

Purpose: To determine the independent prognostic significance of 1p36 loss of heterozygosity (LOH) in a representative group of neuroblastoma patients . Patients and Methods: Diagnostic tumor specimens from 238 patients register ed onto the most recent Children's Cancer Group phase III clinical trials w ere assayed for LOH with 13 microsatellite polymorphic markers spanning chr omosome band 1p36. Allelic status at 1p36 was correlated with other prognos tic variables and disease outcome. Results: LOH at 1p36 was detected in 83 (35%) of 238 neuroblastomas. There was a correlation of 1p36 LOH with age at diagnosis greater than 1 year (P = .026), metastatic disease (P < .001), elevated serum ferritin level (P < .001), unfavorable histopathology (P < .001), and MYCN oncogene amplificati on (P < .001). LOH at 1p36 was associated with decreased event-free surviva l (EFS) and overall survival (OS) probabilities (P < .0001). For the 180 ca ses with single-copy MYCN, 1p36 LOH status was highly correlated with decre ased EFS (P = .0002) but not OS (P = .1212). Entering 1p36 LOH into a multi variate regression model suggested a trend toward an independent associatio n with decreased EFS (P = .0558) but not with decreased OS (P = .3687). Fur thermore, allelic status at 1p36 was the only prognostic variable that was significantly associated with decreased EFS in low-risk neuroblastoma patie nts (P = .0148). Conclusion: LOH at 1p36 is independently associated with decreased EFS, but not OS, in neuroblastoma patients. Determination of 1p36 allelic status ma y be useful for predicting which neuroblastoma patients with otherwise favo rable clinical and biologic features are more likely to have disease progre ssion. (C) 2000 by American Society of Clinical Oncology.