Genetically abnormal circulating cells in lung cancer patients: an antigen-independent fluorescence in situ hybridization-based case-control study.
Genetically abnormal circulating cells in lung cancer patients: an antigen-independent fluorescence in situ hybridization-based case-control study.
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DOI：
10.1158/1078-0432.ccr-09-3358
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发表时间：
2010-08-01
期刊：
影响因子：
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通讯作者：
El-Zein R
中科院分区：
文献类型：
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作者：
Katz RL;He W;Khanna A;Fernandez RL;Zaidi TM;Krebs M;Caraway NP;Zhang HZ;Jiang F;Spitz MR;Blowers DP;Jimenez CA;Mehran RJ;Swisher SG;Roth JA;Morris JS;Etzel CJ;El-Zein R
我们进行了一项研究，以确定基于荧光原位杂交 (FISH) 的检测是否可以检测到循环遗传异常细胞 (CAC)，该检测使用分离的外周血单核细胞 (PBMC) 和针对已知在非小细胞肺癌 (NSCLC) 病例中存在异常的染色体上特定位点的 DNA 探针。我们评估了 59 名 I 期至 IV 期 NSCLC 病例和 24 名对照患者。 PBMC 和匹配的肿瘤与 2 个双色（3p22.1/CEP3 和 10q22.3 [SP-A]/CEP10）和 2 个四色（CEP3、CEP7、CEP17 和 9p21.3 [URO]）和（EGFR、c-MYC、6p11-q11 和 5p15.2 [LAV]）FISH 探针杂交。使用自动荧光扫描仪量化外周血和匹配肿瘤样本中细胞遗传学异常细胞（CAC）的百分比。 CAC 数量根据每毫升血液中 CAC（定义为具有遗传异常的 PBMC）百分比计算，并以每微升血液表示。 NSCLC 患者的 CAC 数量显着高于对照组。 CAC 的平均数量范围为 10q22.3/CEP10 缺失的 7.23±1.32/μl 到 3p22.1/CEP3 缺失的 45.52±7.49/μl。从疾病早期到晚期，3p22.1、10q22.3 和 9p21.3 缺失以及 URO 增加的 CAC 数量显着增加。我们开发了一种灵敏且定量的、不依赖于抗原的 FISH 检测，用于检测 NSCLC 患者外周血中的 CAC，该检测与癌症的存在存在显着相关性。如果这项试点研究能够在更大规模的研究中得到验证，CAC 可能在 NSCLC 患者的治疗中发挥作用。
We performed a study to determine if a fluorescence in-situ hybridization (FISH)-based assay using isolated peripheral blood mononuclear cells (PBMCs) with DNA probes targeting specific sites on chromosomes known to have abnormalities in Non Small Cell Lung Cancer (NSCLC) cases could detect circulating genetically abnormal cells (CACs). We evaluated 59 NSCLC cases with stage I through IV disease and 24 controls. PBMCs and matched tumors were hybridized with 2 two-color (3p22.1/CEP3 and 10q22.3 [SP-A]/CEP10) and 2 four-color (CEP3, CEP7, CEP17, and 9p21.3 [URO]) and (EGFR, c-MYC, 6p11-q11, and 5p15.2 [LAV]) FISH probes. Percentages of cytogenetically abnormal cells (CACs) in peripheral blood and in matched tumor specimens were quantified using an automated fluorescent scanner. Numbers of CACs were calculated based on the percentage of CACs (defined as PBMCs with genetic abnormalities) per mL of blood and expressed per microliter of blood. Patients with NSCLC had significantly higher numbers of CACs than did controls. Mean number of CACs ranged from 7.23±1.32/μl for deletions of 10q22.3/CEP10 to 45.52±7.49/μl for deletions of 3p22.1/CEP3. Numbers of CACs with deletions of 3p22.1, 10q22.3, and 9p21.3, and gains of URO, increased significantly from early to advanced stage of disease. We have developed a sensitive and quantitative antigen-independent FISH-based test for detecting CACs in peripheral blood of patients with NSCLC which showed a significant correlation with the presence of cancer. If this pilot study can be validated in a larger study, CACs may have a role in the management of patients with NSCLC.