Przybyl Joanna, Kozak Katarzyna, Kosela Hanna, Falkowski Slawomir, Switaj Tomasz, Lugowska Iwona, Szumera-Cieckiewicz Anna, Ptaszynski Konrad, Grygalewicz Beata, Chechlinska Magdalena, Pienkowska-Grela Barbara, Debiec-Rychter Maria, Siedlecki Janusz A, Rutkowski Piotr
Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 5 W.K. Roentgen Street, 02-781, Warsaw, Poland,
Med Oncol. 2014 Aug;31(8):109. doi: 10.1007/s12032-014-0109-2. Epub 2014 Jul 10.
Ewing sarcoma (ES) is a group of highly aggressive small round cell tumors of bone or soft tissue with high metastatic potential and low cure rate. ES tumors are associated with a rapid osteolysis and necrosis. The currently accepted clinical prognostic parameters do not accurately predict survival of high-risk patients. Moreover, neither the subtype of EWS-FLI1/ERG in the tumor, nor the detection of fusion transcripts in the peripheral blood (PB) samples, has prognostic value in ES patients. We evaluated the prevalence of circulating tumor cells (CTCs) in 34 adult ES patients. Since CTCs were confirmed in only small subset of patients, we further explored the expression profiles of PB leukocytes using a panel of genes associated with immune system status and increased tumor invasiveness. Moreover, we analyzed the alterations of the routine blood tests in the examined cohort of patients and correlated our findings with the clinical outcome. A uniform decrease in ZAP70 expression in PB cells among all ES patients, as compared to healthy individuals, was observed. Monocytosis and the abnormal expression of CDH2 and CDT2 genes in the PB cells significantly correlated with poor prognosis in ES patients. Our study supports the previously proposed hypothesis of systemic nature of ES. Based on the PB cell expression profiles, we propose a mechanism by which immune system may be involved in intensification of osteoclastogenesis and disease progression in ES patients. Moreover, we demonstrate the prognostic value of molecular PB testing at the time of routine histopathological diagnosis.
尤因肉瘤（ES）是一组侵袭性很强的骨或软组织小圆细胞肿瘤，具有高转移潜能和低治愈率。ES肿瘤与快速的骨溶解和坏死有关。目前公认的临床预后参数不能准确预测高危患者的生存情况。此外，肿瘤中EWS-FLI1/ERG的亚型以及外周血（PB）样本中融合转录本的检测，在ES患者中均无预后价值。我们评估了34例成年ES患者循环肿瘤细胞（CTC）的发生率。由于仅在一小部分患者中证实存在CTC，我们使用一组与免疫系统状态和肿瘤侵袭性增加相关的基因，进一步探索PB白细胞的表达谱。此外，我们分析了所检查患者队列中常规血液检查的变化，并将我们的发现与临床结果相关联。与健康个体相比，在所有ES患者中均观察到PB细胞中ZAP70表达一致下降。PB细胞中的单核细胞增多以及CDH2和CDT2基因的异常表达与ES患者的不良预后显著相关。我们的研究支持了先前提出的ES具有全身性的假说。基于PB细胞表达谱，我们提出了一种免疫系统可能参与ES患者破骨细胞生成增强和疾病进展的机制。此外，我们证明了在常规组织病理学诊断时PB分子检测的预后价值。
