Ladenstein R, Ambros I M, Pötschger U, Amann G, Urban C, Fink F M, Schmitt K, Jones R, Slociak M, Schilling F, Ritter J, Berthold F, Gadner H, Ambros P F
Department of Paediatric Haemato-Oncology, St. Anna Children's Hospital, Vienna, Austria.
Med Pediatr Oncol. 2001 Jan;36(1):83-92. doi: 10.1002/1096-911X(20010101)36:1<83::AID-MPO1020>3.0.CO;2-9.
Identification of biological factors may provide tools to discriminate poor risk neuroblastoma patients of diagnosis, to ultimately offer risk adapted treatment intensity.
Tumour cell DNA content, MYCN amplification (NMA), deletion of the short arm of chromosome 1 (del 1p) as well as three serological markers were assessed in 179 children with neuroblastoma.
Localised regional disease (stage 1 to 3) was diagnosed in 98 patients, and disseminated disease in 81 patients (65 with stage 4, 16 with stage 4s). Median age at diagnosis was 12 months and the median observation time 4 years. Sixty-seven of 179 patients had near di-tetraploid tumours (37%), with a significantly worse prognosis of 44% overall survival at 4 years in comparison with 88% in near triploid tumours (P < .001). The near di-tetraploid group showed a significant correlation with additional adverse biological factors (NMA, del 1p: P < 0.001), age over 1 year (P< 0.001), clinical stage 4 (P< 0.001), elevated ferritin (P = 0.023), and elevated LDH (P< 0.001). Multivariate analysis based on the overall (OS) and event free survival (EFS) estimations revealed that near di-tetraploidy was the most powerful biological factor, with a P-value of <0.001 for EFS and OS, followed by NMA (P = 0.015) for OS and del 1p (P= 0.047) for EFS.
This analysis underlines the important influence of near di-tetraploidy on prognosis, and suggests that more efforts should be undertaken to implement this factor in future studies.
识别生物学因素可为鉴别诊断时风险较高的神经母细胞瘤患者提供工具，从而最终提供适应风险的治疗强度。
对179例神经母细胞瘤患儿的肿瘤细胞DNA含量、MYCN扩增（NMA）、1号染色体短臂缺失（del 1p）以及三种血清学标志物进行了评估。
98例患者诊断为局限性区域疾病（1至3期），81例患者诊断为播散性疾病（65例为4期，16例为4s期）。诊断时的中位年龄为12个月，中位观察时间为4年。179例患者中有67例肿瘤接近二倍体-四倍体（37%），其4年总生存率为44%，与接近三倍体肿瘤的88%相比，预后明显更差（P < 0.001）。接近二倍体-四倍体组与其他不良生物学因素（NMA、del 1p：P < 0.001）、年龄超过1岁（P < 0.001）、临床4期（P < 0.001）、铁蛋白升高（P = 0.023）以及乳酸脱氢酶升高（P < 0.001）显著相关。基于总生存（OS）和无事件生存（EFS）估计的多变量分析显示，接近二倍体-四倍体是最有力的生物学因素，EFS和OS的P值均<0.001，其次是OS的NMA（P = 0.015）和EFS的del 1p（P = 0.047）。
该分析强调了接近二倍体-四倍体对预后的重要影响，并表明未来研究应更加努力将该因素纳入考量。
