使用预后因素的高灵敏度分析组合对神经母细胞瘤进行生物学诊断。

Biological diagnosis for neuroblastoma using the combination of highly sensitive analysis of prognostic factors.

作者信息

Tajiri Tatsuro, Tanaka Shinji, Higashi Mayumi, Kinoshita Yoshiaki, Takahashi Yukiko, Tatsuta Kyosuke, Suita Sachiyo

机构信息

Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.

出版信息

J Pediatr Surg. 2006 Mar;41(3):560-6. doi: 10.1016/j.jpedsurg.2005.11.067.

DOI:10.1016/j.jpedsurg.2005.11.067

PMID:16516635

Abstract

BACKGROUND/PURPOSE: To select the optimal treatment according to the degree of malignancy of neuroblastoma, it is essential to accurately and rapidly identify any genetic abnormalities associated with the prognosis. This study aims to assess the correlation between the combination of prognostic factors and the biologic findings of neuroblastoma using a highly sensitive analysis of prognostic factors.

METHODS

In 44 neuroblastoma primary samples, we determined the gene dosages of MYCN and Survivin (as the target of 17q gain) and the expression levels of MYCN, Survivin, and BIN1 using highly sensitive analysis (the quantitative polymerase chain reaction method); furthermore, we assessed the correlation between the combination of their prognostic factors and the biology of neuroblastoma.

RESULTS

The gene dosage of MYCN or Survivin was significantly associated with all known prognostic factors. The expression level of MYCN or Survivin was not significantly associated with any prognostic factors, whereas the expression level of BIN1 was significantly associated with 5 of 6 prognostic factors. Regarding the combination of MYCN amplification and 17q gain (the gene dosage of Survivin), and the low expression of BIN1, the rates of advanced stages (stage III or IV) were 100% for the cases with 3 factors, 63% for the cases with 2 factors, 42% for the cases with 1 factor, and 0% for the cases with null factor. Furthermore, the survival rates were 20% for the cases with 3 factors, 50% for the cases with 2 factors, 100% for the cases with 1 factor, and 100% for the cases with null factor.

CONCLUSION

The combination of gene dosages of MYCN and Survivin and the expression level of BIN1 using the quantitative polymerase chain reaction method was significantly correlated with the clinical stage and the patients' outcome. This combination of biologic factors may enhance the accuracy to the conventional criteria, but this would have to be shown in a much larger study that is adequately powered to detect such an advantage.

摘要

背景/目的：为了根据神经母细胞瘤的恶性程度选择最佳治疗方案，准确、快速地识别与预后相关的任何基因异常至关重要。本研究旨在通过对预后因素进行高度敏感分析，评估预后因素组合与神经母细胞瘤生物学表现之间的相关性。

方法

在44例神经母细胞瘤原发样本中，我们使用高度敏感分析（定量聚合酶链反应法）测定了MYCN和Survivin（作为17q增益的靶点）的基因剂量以及MYCN、Survivin和BIN1的表达水平；此外，我们评估了它们的预后因素组合与神经母细胞瘤生物学特性之间的相关性。

结果

MYCN或Survivin的基因剂量与所有已知的预后因素显著相关。MYCN或Survivin的表达水平与任何预后因素均无显著相关性，而BIN1的表达水平与6个预后因素中的5个显著相关。关于MYCN扩增与17q增益（Survivin的基因剂量）以及BIN1低表达的组合，具有3个因素的病例晚期（III期或IV期）发生率为100%，具有2个因素的病例为63%，具有1个因素的病例为42%，无因素的病例为0%。此外，具有3个因素的病例生存率为20%，具有2个因素的病例为50%，具有1个因素的病例为100%，无因素的病例为100%。