Shen Q, Shen L S, Chen Q, Zhou J Y, Zhou J Y
Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Zhejiang University Medical College, Hangzhou 310003, China.
Zhonghua Jie He He Hu Xi Za Zhi. 2018 Oct 12;41(10):772-777. doi: 10.3760/cma.j.issn.1001-0939.2018.10.005.
This study explored the value of circulating tumor cells (CTC) detected by chromosome 8 centromere probe in diagnosis of non-small cell lung cancer (NSCLC) as well as correlation between CTC counts and clinical pathological characteristics. We collected 136 patients with newly diagnosed NSCLC (101 males and 35 females, age ranged from 34 to 79 years), 149 patients with non-malignant pulmonary diseases (103 males and 46 females, age ranged from 24 to 80 years) and 32 healthy volunteers (5 males and 27 females, age ranged from 24 to 42 years). Detection was performed using an epithelial cell adhesion molecule-independent strategy that combined immunocytochemistry staining (ICC) of CD(45) and fluorescence in situ hybridization detection (FISH) with chromosome 8 centromere probe (CEP8). CTC was defined as 4',6-diamidino-2-phenylindole (DAPI) positive, CD(45) negative and CEP8 more than 2 positive points. Quantitative data were reported as ± and Mann Whitney test was used to compare them. Measurement data were analyzed as contingency tables and Pearson chi-squared test was used. values of less than 0.05 were considered statistically significant. CTCs were detected in 114 patients (83.8%) with NSCLC, 35 patients (23.5%) with non-malignant pulmonary diseases (0.000 1) and 5 volunteers (15.6%). CTC counts in NSCLC patients were (5.98±0.64) per 3.2 ml and (0.60±0.13) per 3.2 ml (0.000 1). A receiver operating characteristic curve (ROC) analysis showed similar capability of CTC count, with CEA, in discriminating NSCLC and non-malignant diseases with an area under ROC curve of 0.854 (95% confidence interval: 0.808-0.900, 0.001). Cutoff of 2 circulating tumor cells per 3.2 ml peripheral blood gave the highest Youden Index of 0.614 in diagnosis of NSCLC with sensitivity of 72.1% (98/136) and specificity of 89.3% (133/149). When patients with CTC≥2/3.2 ml peripheral blood or serum CEA≥5 ng/ml were considered as having NSCLC, sensitivity and specificity of this combined test were 87.5% (119/136) and 85.9% (128/149), with a higher Youden Index of 0.734. No correlation was observed between positive rate of CTC (rate of patients with CTC≥2/3.2 ml peripheral blood) and age, gender, smoking status, pathologic types, and clinical stages. CTC counts detected by CD(45)-FISH is higher in NSCLC patients than in non-malignant disease patients. CTC≥2/3.2 ml peripheral blood is valuable in discriminating NSCLC from nonmalignant diseases, which can be more accurate when combined with CEA.
本研究探讨了采用8号染色体着丝粒探针检测循环肿瘤细胞（CTC）在非小细胞肺癌（NSCLC）诊断中的价值以及CTC计数与临床病理特征之间的相关性。我们收集了136例新诊断的NSCLC患者（男性101例，女性35例，年龄34至79岁）、149例非恶性肺疾病患者（男性103例，女性46例，年龄24至80岁）和32名健康志愿者（男性5例，女性27例，年龄24至42岁）。采用一种不依赖上皮细胞粘附分子的策略进行检测，该策略将CD(45)的免疫细胞化学染色（ICC）与8号染色体着丝粒探针（CEP8）的荧光原位杂交检测（FISH）相结合。CTC定义为4',6-二脒基-2-苯基吲哚（DAPI）阳性、CD(45)阴性且CEP8阳性点数超过2个。定量数据以±表示，并采用Mann-Whitney检验进行比较。计量资料以列联表分析，并采用Pearson卡方检验。P值小于0.05被认为具有统计学意义。在114例（83.8%）NSCLC患者、35例（23.5%）非恶性肺疾病患者（P<0.0001）和5名志愿者（15.6%）中检测到CTC。NSCLC患者的CTC计数为每3.2 ml（5.98±0.64）个，非恶性肺疾病患者为每3.2 ml（0.60±0.13）个（P<0.0001）。受试者工作特征曲线（ROC）分析显示，CTC计数与癌胚抗原（CEA）在鉴别NSCLC和非恶性疾病方面具有相似的能力，ROC曲线下面积为0.854（95%置信区间：0.808 - 0.900，P<0.001）。每3.2 ml外周血中循环肿瘤细胞截断值为2个时，在NSCLC诊断中具有最高的约登指数0.614，敏感性为72.1%（98/136），特异性为89.3%（133/149）。当外周血中CTC≥2/3.2 ml或血清CEA≥5 ng/ml的患者被视为患有NSCLC时，该联合检测的敏感性和特异性分别为87.5%（119/136）和85.9%（128/149），约登指数更高，为0.734。未观察到CTC阳性率（外周血中CTC≥2/3.2 ml的患者比例）与年龄、性别、吸烟状况、病理类型及临床分期之间存在相关性。通过CD(45)-FISH检测到的NSCLC患者的CTC计数高于非恶性疾病患者。外周血中CTC≥2/3.2 ml对于鉴别NSCLC与非恶性疾病具有价值，与CEA联合使用时可能更准确。
