11q23 染色体带缺失预示着无 MYCN 扩增的骨髓转移神经母细胞瘤患者预后不良。
Chromosome band 11q23 deletion predicts poor prognosis in bone marrow metastatic neuroblastoma patients without MYCN amplification.
机构信息
Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, MOE Key Laboratory of Major Diseases in Children Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 Nanlishi Road, Beijing, 100045, People's Republic of China.
出版信息
Cancer Commun (Lond). 2019 Nov 4;39(1):68. doi: 10.1186/s40880-019-0409-1.
BACKGROUND
Interphase fluorescence in situ hybridization (FISH) of bone marrow cells has been confirmed to be a direct and valid method to assess the v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) amplification in patients with bone marrow metastatic neuroblastoma. MYCN amplification alone, however, is insufficient for pretreatment risk stratification. Chromosome band 11q23 deletion has recently been included in the risk stratification of neuroblastoma. In the present study, we aimed to evaluate the biological characteristics and prognostic impact of 11q23 deletion and MYCN amplification in patients with bone marrow metastatic neuroblastoma.
METHODS
We analyzed the MYCN and 11q23 statuses of 101 patients with bone marrow metastatic neuroblastoma using interphase FISH of bone marrow cells. We specifically compared the biological characteristics and prognostic impact of both aberrations.
RESULTS
MYCN amplification and 11q23 deletion were seen in 12 (11.9%) and 40 (39.6%) patients. The two markers were mutually exclusive. MYCN amplification occurred mainly in patients with high lactate dehydrogenase (LDH) and high neuron-specific enolase (NSE) levels (both P < 0.001), and MYCN-amplified patients had more events (tumor relapse, progression, or death) than MYCN-normal patients (P = 0.004). 11q23 deletion was associated only with age (P = 0.001). Patients with MYCN amplification had poorer outcomes than those with normal MYCN (3-year event-free survival [EFS] rate: 8.3 ± 8.0% vs. 43.8 ± 8.5%, P < 0.001; 3-year overall survival [OS] rate: 10.4 ± 9.7% vs. 63.5% ± 5.7%, P < 0.001). 11q23 deletion reflected a poor prognosis only for patients with normal MYCN (3-year EFS rate: 34.3 ± 9.5% vs. 53.4 ± 10.3%, P = 0.037; 3-year OS rate: 42.9 ± 10.4% vs. 75.9 ± 6.1%, P = 0.048). Those with both MYCN amplification and 11q23 deletion had the worst outcome (P < 0.001).
CONCLUSIONS
Chromosome band 11q23 deletion predicts poor prognosis only in bone marrow metastatic neuroblastoma patients without MYCN amplification. Combined assessment of the two markers was much superior to single-marker assessment in recognizing the patients at a high risk of disease progression.
背景
骨髓细胞的间期荧光原位杂交（FISH）已被证实是一种直接有效的方法，可用于评估骨髓转移性神经母细胞瘤患者中 v-myc 禽髓细胞瘤病毒致癌基因神经母细胞瘤衍生同源物（MYCN）扩增。然而，仅 MYCN 扩增不足以进行预处理风险分层。染色体 11q23 缺失最近已被纳入神经母细胞瘤的风险分层中。本研究旨在评估骨髓转移性神经母细胞瘤中 11q23 缺失和 MYCN 扩增的生物学特征和预后影响。
方法
我们使用骨髓细胞的间期 FISH 分析了 101 例骨髓转移性神经母细胞瘤患者的 MYCN 和 11q23 状态。我们特别比较了两种异常的生物学特征和预后影响。
结果
12 例（11.9%）和 40 例（39.6%）患者存在 MYCN 扩增和 11q23 缺失。这两个标志物是互斥的。MYCN 扩增主要发生在乳酸脱氢酶（LDH）和神经元特异性烯醇化酶（NSE）水平较高的患者中（均 P<0.001），且 MYCN 扩增患者的事件（肿瘤复发、进展或死亡）多于 MYCN 正常患者（P=0.004）。11q23 缺失仅与年龄有关（P=0.001）。与 MYCN 正常患者相比，MYCN 扩增患者的预后较差（3 年无事件生存率[EFS]率：8.3±8.0%比 43.8±8.5%，P<0.001；3 年总生存率[OS]率：10.4±9.7%比 63.5%±5.7%，P<0.001）。11q23 缺失仅对 MYCN 正常的患者预示着不良预后（3 年 EFS 率：34.3±9.5%比 53.4±10.3%，P=0.037；3 年 OS 率：42.9±10.4%比 75.9±6.1%，P=0.048）。同时存在 MYCN 扩增和 11q23 缺失的患者预后最差（P<0.001）。
结论
染色体 11q23 缺失仅在无 MYCN 扩增的骨髓转移性神经母细胞瘤患者中预示着不良预后。两种标志物的联合评估比单一标志物评估更能识别疾病进展风险较高的患者。
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