Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
Department of Nuclear Medicine, Huashan Hospital, Fudan University, Shanghai, China.
J Cell Physiol. 2018 Jun;233(6):5014-5022. doi: 10.1002/jcp.26353. Epub 2018 Jan 4.
Circulating tumor cells (CTCs) are an important topic of investigation for both basic and clinical cancer research. In this prospective study, we evaluated the clinical role of CTCs in ampullary cancer. We analyzed blood samples from 62 consecutively diagnosed patients with ampullary adenocarcinoma and 24 healthy controls for their CTC content. Combined data from immunostaining of CD45, 4',6-diamidino-2-phenylindole (DAPI), and fluorescence in situ hybridization with a chromosome 8 centromere (CEP8) probe were used to identify CTCs; cells that were CD45-/DAPI+/CEP8>2 were considered CTCs. The Cox proportional hazards model was used to assess the relationship between CTCs, clinical characteristics, and patient outcomes. We detected ≥2 CTCs/3.2 ml whole blood in 43 of 62 patients (69.4%), as well as ≥5 CTCs/3.2 ml in 16 of these patients (25.8%). A CTC cutoff value of 2 cells/3.2 ml achieved 69.4% sensitivity and 95.8% specificity as a diagnostic tool; CTCs were associated with tumor burden. CTC levels ≥3/3.2 ml (hazard ratio [HR]: 2.5, 95% confidence interval [CI]: (1.2-5.2), p = 0.014) and ≥5/3.2 ml (HR: 3.5, 95% CI: 1.7-7.3, p < 0.001) were both associated with shorter disease-free survival. Moreover, ≥3 CTCs/3.2 ml (HR: 2.7, 95% CI: 1.2-6.3, p = 0.019) and ≥5 CTCs/3.2 ml (HR: 3.8, 95% CI: 1.8-8.5, p < 0.001) were predictive of shorter overall survival. CTC assessment may help identify patients with ampullary cancer who are at high risk of an unfavorable outcome.
循环肿瘤细胞 (CTCs) 是基础和临床癌症研究的一个重要课题。在这项前瞻性研究中,我们评估了 CTCs 在壶腹腺癌中的临床作用。我们分析了 62 例连续诊断为壶腹腺癌患者和 24 例健康对照者的血液样本,以检测其 CTC 含量。使用 CD45、4',6-二脒基-2-苯基吲哚 (DAPI) 和染色体 8 着丝粒 (CEP8) 探针的免疫染色的综合数据来识别 CTCs;CD45-/DAPI+/CEP8>2 的细胞被认为是 CTCs。使用 Cox 比例风险模型评估 CTCs、临床特征和患者结局之间的关系。我们在 62 例患者中的 43 例 (69.4%) 中检测到≥2 CTCs/3.2 ml 全血,在这些患者中的 16 例 (25.8%) 中检测到≥5 CTCs/3.2 ml 全血。CTC 截断值为 2 个细胞/3.2 ml 时,作为诊断工具的灵敏度为 69.4%,特异性为 95.8%;CTC 与肿瘤负荷相关。CTC 水平≥3/3.2 ml (危险比 [HR]:2.5,95%置信区间 [CI]:(1.2-5.2),p=0.014) 和≥5/3.2 ml (HR:3.5,95%CI:1.7-7.3,p<0.001) 均与无疾病生存期较短相关。此外,≥3 CTCs/3.2 ml (HR:2.7,95% CI:1.2-6.3,p=0.019) 和≥5 CTCs/3.2 ml (HR:3.8,95% CI:1.8-8.5,p<0.001) 均可预测总生存期较短。CTC 评估可能有助于识别壶腹癌患者中预后不良风险较高的患者。