Druĭ A E, Shorikov E V, Tsaur G A, Popov A M, Tuponogov S N, Savel'ëv L I, Tsvirenko S V, Fechina L G
Vopr Onkol. 2014;60(2):57-62.
Bone marrow (BM) involvement in neuroblastoma patients is commonly detected by cytomorphology and associated with poor outcome. Molecular techniques, flow cytometry and immunocytochemistry were offered to detect low number of tumor cells in BM due to high value of analytical sensitivity, while prognostic significance of results, obtained with these methods is unclear. PHOX2B and/or TH genes expression was selected as molecular marker of BM involvement. It was determined in 411 BM samples obtained from 75 neuroblastoma patients. 263 BM samples were taken at the time of primary diagnosis, 80 during treatment and 68 before autologous stem cells (ASC) apheresis. Prognostic significance of BM involvement was defined using 5-year (in some groups 4-year) overall (OS), event free (EFS) and progression free (PFS) survival. 24 patients (32.0%) were positive for PHOX2B and/or TH expression in the BM at the time of primary diagnosis. They had decreased survival rates: EFS achieved 0.49+/-0.12, OS - 0.57+/-0.12, PFS - 0.54+/-0.12, comparing with 0.75+/-0.07, 0.80+/-0.07 and 0.77+/-0.07, respectively, in patients with negative BM, p=0.014, p=0.029 and p=0.033. The trend to decreased OS and PFS was detected in case of minimal residual disease presence at the end of the induction chemotherapy (OS and PFS both are 0.22+/-0.19 vs. 0.70+/-0.18 and 0.43+/-0.22, correspondingly, p=0.121, p=0.130). Detection of PHOX2B and/or TH genes expression in the BM before ASC harvesting led to significant decreasing of EFS and OS (0.00 vs. 0.59+/-0.14 and 0.75+/-0.13, respectively, p=0.021 and p=0.016).
神经母细胞瘤患者的骨髓（BM）受累情况通常通过细胞形态学检测，且与预后不良相关。由于分析灵敏度高，分子技术、流式细胞术和免疫细胞化学被用于检测骨髓中数量较少的肿瘤细胞，然而，用这些方法获得的结果的预后意义尚不清楚。选择PHOX2B和/或TH基因表达作为骨髓受累的分子标志物。在从75例神经母细胞瘤患者获取的411份骨髓样本中进行了检测。263份骨髓样本在初次诊断时采集，80份在治疗期间采集，68份在自体干细胞（ASC）采集前采集。使用5年（部分组为4年）总生存（OS）、无事件生存（EFS）和无进展生存（PFS）来确定骨髓受累的预后意义。24例患者（32.0%）在初次诊断时骨髓中PHOX2B和/或TH表达呈阳性。与骨髓阴性的患者相比，他们的生存率降低：EFS为0.49±0.12，OS为0.57±0.12，PFS为0.54±0.12，而骨髓阴性患者的EFS、OS和PFS分别为0.75±0.07、0.80±0.07和0.77±0.07，p = 0.014、p = 0.029和p = 0.033。在诱导化疗结束时存在微小残留病的情况下，检测到OS和PFS有下降趋势（OS和PFS分别为0.22±0.19与0.70±0.18以及0.43±0.22，相应地，p = 0.121，p = 0.130）。在ASC采集前检测到骨髓中PHOX2B和/或TH基因表达导致EFS和OS显著降低（分别为0.00与0.59±0.14以及0.75±0.13，p = 0.021和p = 0.016）。
