Department of Pathology, Basic Medical College, Capital Medical University, Beijing, China.
Exp Mol Pathol. 2013 Oct;95(2):124-30. doi: 10.1016/j.yexmp.2013.06.002. Epub 2013 Jun 21.
ALK gene has been identified as a major neuroblastoma (NBL) predisposition gene. But ALK gene copy number and protein expression in ganglioneuroblastoma (GNBL) and ganglioneuroma (GN) are poorly described in the literature. Furthermore, there are controversies on the correlation between ALK protein expression and clinical outcome in NBL.
We evaluated MYCN/ALK gene copy number by fluorescence in situ hybridization (FISH) and detected ALK protein expression by immunohistochemistry (IHC) in 188 NBL, 52 GNBL and 6 GN samples and analyzed their association with clinical outcome of the patients.
Although ALK gene copy number increase is a recurrent genetic aberration of neuroblastic tumors (NTs) (39.1%, 96/246), ALK amplification was only present in three NBLs (1.2%, 3/246). The frequency of ALK positivity in NBL (50.5%, 51/101) was significantly higher than in GNBL (22.6%, 7/31) and in GN (0.0%, 0/4) (P<0.05). In addition, ALK positivity also significantly correlates with MYCN/ALK gene copy number increases (P<0.05). Kaplan-Meier survival analysis indicated that MYCN/ALK amplification is correlated with decreased overall survival in NBL. A better prognosis trend was observed in patients with MYCN/ALK gain tumors compared with those with MYCN/ALK normal tumors. Furthermore, ALK positivity significantly correlated with inferior survival in NBL (P=0.044).
ALK positivity in NTs correlated with advanced tumor types and MYCN/ALK gene copy number increases. ALK positivity predicts inferior prognosis in NBL and IHC is a simplified strategy to screen ALK positivity in clinical practice.
ALK 基因已被确定为神经母细胞瘤（NBL）的主要易患基因。但是，文献中对神经节母细胞瘤（GNBL）和神经节细胞瘤（GN）中 ALK 基因拷贝数和蛋白表达的描述甚少。此外，ALK 蛋白表达与 NBL 临床结果之间的相关性存在争议。
我们通过荧光原位杂交（FISH）评估了 MYCN/ALK 基因拷贝数，并通过免疫组织化学（IHC）检测了 188 例 NBL、52 例 GNBL 和 6 例 GN 样本中的 ALK 蛋白表达，并分析了它们与患者临床结果的关系。
尽管 ALK 基因拷贝数增加是神经母细胞瘤（NTs）的常见遗传异常（39.1%，96/246），但仅在 3 例 NBL 中发现 ALK 扩增（1.2%，3/246）。NBL 中 ALK 阳性率（50.5%，51/101）明显高于 GNBL（22.6%，7/31）和 GN（0.0%，0/4）（P<0.05）。此外，ALK 阳性与 MYCN/ALK 基因拷贝数增加显著相关（P<0.05）。Kaplan-Meier 生存分析表明，MYCN/ALK 扩增与 NBL 患者总生存率降低相关。与 MYCN/ALK 正常肿瘤患者相比，具有 MYCN/ALK 增益肿瘤的患者具有更好的预后趋势。此外，ALK 阳性与 NBL 患者的生存预后显著相关（P=0.044）。
NT 中的 ALK 阳性与晚期肿瘤类型和 MYCN/ALK 基因拷贝数增加相关。ALK 阳性预测 NBL 预后不良，IHC 是筛选临床实践中 ALK 阳性的简化策略。
