Department of Pathology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
Malhotra Super Specialty Hospital, Baddi, India.
Virchows Arch. 2023 Oct;483(4):477-486. doi: 10.1007/s00428-023-03604-8. Epub 2023 Jul 17.
Neuroblastoma (NB) is the most common extracranial solid tumour in childhood with a diverse clinical presentation and course. The early age of onset, high frequency of metastatic disease at diagnosis and tendency for spontaneous regression in infancy sets it apart from other childhood tumors. This heterogeneity is largely attributed to underlying genetic aberrations which are distinct in low-risk and high-risk NB. To this end, we sought to analyse our NB cases for the molecular alterations and find its correlation with clinical behaviour.
NB cases (n = 50) diagnosed over last 7 years were retrospectively analysed for MYCN amplification (fluorescent-in-situ hybridization), TERT rearrangements (qRT-PCR), ATRX mutations (immunohistochemistry). These findings were correlated with demographic profiles, histologic features and clinical outcome.
Age ranged from 1 month to 30 years (mean 2.8 years) with male preponderance. Poorly differentiated subtype constituted the majority (64%), followed by differentiating (28%) and undifferentiated subtype (8%) which were equally distributed across all age groups. MYCN amplification, TERT-mRNA upregulation and ATRX mutations was observed in 30%, 42% and 24%, respectively. Cases with TERT-mRNA upregulation were distributed equally across all histological subtypes while those with ATRX mutations and MYCN amplification were frequent in poorly differentiated NB. ATRX mutation was mutually exclusive of TERT-mRNA upregulation and MYCN amplification. Kaplan-Meier analysis revealed significantly shorter overall and progression-free survival for tumors harboring MYCN amplification and TERT-mRNA upregulation, while that for ATRX mutant tumors was not significant.
Our results provide data indicating poor clinical outcome in NB carrying MYCN amplification and TERT-mRNA upregulation.
神经母细胞瘤（NB）是儿童期最常见的颅外实体瘤，具有多种临床表现和病程。其发病年龄早，诊断时转移性疾病的发生率高，婴儿期自发消退的趋势使其有别于其他儿童肿瘤。这种异质性在很大程度上归因于潜在的遗传异常，这些异常在低风险和高风险 NB 中是不同的。为此，我们试图分析我们的 NB 病例中的分子改变，并发现其与临床行为的相关性。
回顾性分析了过去 7 年来诊断的 50 例 NB 病例，分析了 MYCN 扩增（荧光原位杂交）、TERT 重排（qRT-PCR）、ATRX 突变（免疫组化）。将这些发现与人口统计学特征、组织学特征和临床结果相关联。
年龄从 1 个月到 30 岁（平均 2.8 岁），男性居多。分化不良型占大多数（64%），其次是分化型（28%）和未分化型（8%），它们在所有年龄组中分布均匀。观察到 30%的病例存在 MYCN 扩增，42%的病例存在 TERT-mRNA 上调，24%的病例存在 ATRX 突变。TERT-mRNA 上调的病例在所有组织学亚型中分布均匀，而 ATRX 突变和 MYCN 扩增的病例在分化不良的 NB 中较为常见。ATRX 突变与 TERT-mRNA 上调相互排斥。Kaplan-Meier 分析显示，携带 MYCN 扩增和 TERT-mRNA 上调的肿瘤的总生存期和无进展生存期明显缩短，而 ATRX 突变肿瘤的生存期无显著差异。
我们的结果提供了数据表明，携带 MYCN 扩增和 TERT-mRNA 上调的 NB 具有不良的临床预后。
