未分化型神经母细胞瘤，核仁明显形成的预后意义，以及 MYC/MYCN 蛋白表达：来自儿童肿瘤协作组的报告。
Neuroblastoma of undifferentiated subtype, prognostic significance of prominent nucleolar formation, and MYC/MYCN protein expression: a report from the Children's Oncology Group.
机构信息
Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles and University of Southern California Keck School of Medicine, Los Angeles, California.
出版信息
Cancer. 2013 Oct 15;119(20):3718-26. doi: 10.1002/cncr.28251. Epub 2013 Jul 30.
BACKGROUND
This study sought to investigate biological/clinicopathological characteristics of neuroblastoma, undifferentiated subtype (NBUD).
METHODS
This study examined 157 NBUD cases filed at the Children's Oncology Group Neuroblastoma Pathology Reference Laboratory, and survival rates of the patients were analyzed with known prognostic factors. Immunostainings for MYCN and MYC protein were performed on 68 tumors.
RESULTS
NBUD cases had a poor prognosis (48.4% ± 5.0% 3-year event-free survival [EFS]; 56.5% ± 5.0% overall survival [OS]), and were often associated with high mitosis-karyorrhexis index (MKI, 65%), prominent nucleoli (PN, 83%), ≥ 18 months of age (75%), MYCN amplification (MYCN-A, 83%), diploid pattern (63%), and 1pLOH (loss of heterozygosity (72%). However, these prognostic indicators, except for MYCN status, had no significant impact on survival. Surprisingly, EFS for patients with MYCN-A tumors (53.4% ± 5.6%) was significantly better (P=.0248) than for patients with MYCN-nonamplified (MYCN-NA) tumors (31.7% ± 11.7%), with MYCN-NA and PN (+) tumors having the worst prognosis (9.3% ± 8.8%, P=.0045). Immunohistochemically, MYCN expression was found in 42 of 48 MYCN-A tumors. In contrast, MYC expression was almost exclusively found in the MYCN-NA tumors (9 of 20) especially when they had PN (8 of 11). Those patients with only MYC-positive tumors had the worst EFS (N=8, 12.5% ± 11.7%) compared with only MYCN-positive (N=39, 49.9% ± 17.7%) and both negative tumors (N=15, 70.0% ± 17.1%) (P= .0029). High MKI was often found in only MYCN-positive (30 of 38) but rarely in only MYC-positive (2 of 8) tumors.
CONCLUSIONS
NBUD represents a unique subtype of neuroblastoma associated with a poor prognosis. In this subtype, MYC protein expression may be a new prognostic factor indicating more aggressive clinical behavior than MYCN amplification and subsequent MYCN protein expression.
背景
本研究旨在探讨未分化型神经母细胞瘤（NBUD）的生物学/临床病理特征。
方法
本研究共检测了儿童肿瘤组神经母细胞瘤病理学参考实验室的 157 例 NBUD 病例，分析了已知预后因素与患者生存率的关系。对 68 例肿瘤进行 MYCN 和 MYC 蛋白免疫染色。
结果
NBUD 病例预后较差（3 年无事件生存率（EFS）为 48.4%±5.0%；总生存率（OS）为 56.5%±5.0%），常伴有高有丝分裂-核碎裂指数（MKI，65%）、明显核仁（PN，83%）、≥18 个月（75%）、MYCN 扩增（MYCN-A，83%）、二倍体模式（63%）和 1pLOH（杂合性丢失（72%）。然而，除 MYCN 状态外，这些预后指标对生存均无显著影响。令人惊讶的是，具有 MYCN-A 肿瘤的患者的 EFS（53.4%±5.6%）明显优于具有 MYCN-非扩增（MYCN-NA）肿瘤的患者（31.7%±11.7%），具有 MYCN-NA 和 PN（+）肿瘤的患者预后最差（9.3%±8.8%，P=.0045）。免疫组化显示，48 例 MYCN-A 肿瘤中有 42 例表达 MYCN。相比之下，MYC 表达几乎仅存在于 MYCN-NA 肿瘤中（20 例中有 9 例），尤其是当肿瘤具有 PN 时（11 例中有 8 例）。仅 MYC 阳性肿瘤患者的 EFS 最差（N=8，12.5%±11.7%），与仅 MYCN 阳性（N=39，49.9%±17.7%）和均为阴性（N=15，70.0%±17.1%）的患者相比（P=0.0029）。高 MKI 常存在于仅 MYCN 阳性（38 例中有 30 例）肿瘤中，而仅 MYC 阳性（8 例中有 2 例）肿瘤中很少存在。
结论
NBUD 是一种具有独特临床病理特征的神经母细胞瘤亚型，预后较差。在该亚型中，MYC 蛋白表达可能是一种新的预后因素，提示比 MYCN 扩增和随后的 MYCN 蛋白表达更具侵袭性的临床行为。
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