Objective: The study was to assess whether tumour expressions of hypoxia-inducible factor (HIF)-1α, glucose transporter (GLUT)-1, carbonic anhydrase (CA) IX and vascular endothelial growth factor (VEGF) predict response to neo-adjuvant chemotherapy (naCHT) in children with inoperable rhabdomyosarcoma (RMS). Methods: Immunohistochemical expressions of hypoxia markers were determined semi-quantitatively in tumour tissue microarray of 46 patients with embryonal RMS (RME) and 20 with alveolar (RMA), treated with CWS protocols (1992-2013). Results: In paediatric RME, response to naCHT was influenced significantly by tumour expression of CA IX and GLUT-1. Patients with RMA with low expressions of analysed markers responded well to naCHT, while all poor-responders expressed highly hypoxia markers. Only 5.88% of RMA and 11.11% of RME tumours did not express any of the proteins. In both RME and RMA subgroups, most poor-responders demonstrated simultaneous high expression of ≥3 markers, while most patients expressing ≤2 markers responded well to naCHT. In the whole cohort, co-expression of ≥3 markers, was the only independent factor predicting poor-response to chemotherapy (odds ratio 14.706; 95% CI 1.72-125.75; p = 0.014). Conclusions: Immunohistochemical expression pattern of four endogenous markers of hypoxia, in tumour tissue at diagnosis, emerges as a promising tool to predict response to naCHT in children with inoperable RMS.

中文翻译：

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缺氧标记物的肿瘤表达预示着无法手术的横纹肌肉瘤患儿对新辅助化疗的反应。

目的：研究缺氧诱导因子（HIF）-1α，葡萄糖转运蛋白（GLUT）-1，碳酸酐酶（CA）IX和血管内皮生长因子（VEGF）的肿瘤表达是否可预测对新辅助化疗的反应（naCHT）在不能手术的横纹肌肉瘤（RMS）患儿中。方法：采用CWS方案（1992-2013），对46例胚胎RMS（RME）和20例肺泡（RMA）患者的肿瘤组织微阵列中半定量检测低氧标志物的免疫组织化学表达。结果：在儿科RME中，CAIX和GLUT-1的肿瘤表达显着影响对naCHT的反应。RMA患者中分析标记物的低表达患者对naCHT的反应良好，而所有反应较差的患者均表达高度缺氧的标记物。只有RMA的5.88％和11。11％的RME肿瘤不表达任何蛋白质。在RME和RMA亚组中，大多数反应较差的人同时表现出≥3个标志物的高表达，而大多数表达≤2个标志物的患者对naCHT的反应良好。在整个队列中，≥3个标志物的共表达是预测对化疗反应不良的唯一独立因素（优势比14.706； 95％CI 1.72-125.75； p = 0.014）。结论：在诊断时，肿瘤组织中四种内源性缺氧标记物的免疫组织化学表达模式成为预测无法手术RMS患儿对naCHT应答的有前途的工具。≥3个标志物的共表达是预测对化疗反应不良的唯一独立因素（赔率14.706； 95％CI 1.72-125.75； p = 0.014）。结论：在诊断时，肿瘤组织中四种内源性缺氧标记物的免疫组织化学表达模式成为预测无法手术RMS患儿对naCHT应答的有前途的工具。≥3个标志物的共表达是预测对化疗反应不良的唯一独立因素（赔率14.706； 95％CI 1.72-125.75； p = 0.014）。结论：在诊断时，肿瘤组织中四种内源性缺氧标记物的免疫组织化学表达模式成为预测无法手术RMS患儿对naCHT应答的有前途的工具。