Department of Pediatrics, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Cancer Res Treat. 2016 Oct;48(4):1399-1407. doi: 10.4143/crt.2015.481. Epub 2016 Mar 24.
The purpose of this study is to investigate the clinical significance of tyrosine hydroxylase (TH) expression in peripheral blood (PB) at diagnosis in patients with neuroblastoma.
mRNA expression in PB was measured by reverse transcription quantitative real-time polymerase chain reaction in 210 patients who were newly diagnosed with neuroblastoma from July 2005 to June 2015 and the clinical significance of expression in PB at diagnosis was evaluated.
expression was positive in 60 patients (28.6%). Fifty of 60 -positive patients had metastatic tumors and the remaining 10 had localized tumors. expression was associated with high-risk features (i.e., advanced stage, older age, unfavorable pathology, and amplification) at diagnosis. Among -positive patients, higher expression level was observed in high-risk patients than in low- or intermediate-risk patients (p=0.035). The probability of 5-year progression-free survival (PFS) was lower in -positive patients than in -negative patients (63.8±6.9% vs. 94.7±2.1%, p < 0.001). In analysis confined to high-risk patients, the 5-year probability of PFS remained lower in -positive patients (55.7±8.2% vs. 89.6±5.8%, p < 0.001). Among -positive patients, a higher expression level of was associated with a worse outcome. In multivariate analyses, positive expression in PB at diagnosis was an independent poor prognostic factor for PFS.
The treatment intensity should be tailored according to expression in PB at diagnosis.
本研究旨在探讨酪氨酸羟化酶(TH)在神经母细胞瘤患者外周血(PB)诊断时的表达的临床意义。
采用逆转录定量实时聚合酶链反应检测 2005 年 7 月至 2015 年 6 月新诊断的 210 例神经母细胞瘤患者 PB 中的 mRNA 表达,并评估诊断时 PB 中表达的临床意义。
60 例患者(28.6%)表达阳性。60 例阳性患者中 50 例有转移瘤,其余 10 例为局限性肿瘤。诊断时表达与高危特征(即晚期、年龄较大、不良病理和扩增)相关。在阳性患者中,高危患者的表达水平高于低危或中危患者(p=0.035)。与阴性患者相比,阳性患者的 5 年无进展生存率(PFS)较低(63.8±6.9% vs. 94.7±2.1%,p < 0.001)。在高危患者的分析中,阳性患者的 5 年 PFS 率仍较低(55.7±8.2% vs. 89.6±5.8%,p < 0.001)。在阳性患者中,较高的表达水平与预后较差相关。多变量分析显示,PB 中诊断时阳性 TH 表达是 PFS 的独立不良预后因素。
应根据 PB 中诊断时的表达来调整治疗强度。