Hinz Sebastian, Hendricks Alexander, Wittig Amke, Schafmayer Clemens, Tepel Jürgen, Kalthoff Holger, Becker Thomas, Röder Christian
Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller Str. 7, 24105, Kiel, Germany.
Division Molecular Oncology, Institute for Experimental Cancer Research, Cancer Center North, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller Str. 7, 24105, Kiel, Germany.
BMC Cancer. 2017 Jan 13;17(1):53. doi: 10.1186/s12885-016-3035-1.
Detection of circulating (CTC) or disseminated tumor cells (DTC) has been associated with negative prognosis and outcome in patients with colorectal cancer, though testing for these cells is not yet part of clinical routine. There are several different methodological approaches to detect tumor cells but standardized detection assays are not implemented so far.
In this prospective monocentric study 299 patients with colon cancer were included. CTC and DTC were detected using CK20 RT-PCR as well as immunocytochemistry staining with anti-pan-keratin and anti-EpCAM antibodies. The primary endpoints were: Evaluation of CTC and DTC at the time of surgery and correlation with main tumor characteristics and overall (OS) and disease free survival (DFS).
Patients with detectable CTC had a 5-year OS rate of 68% compared to a 5-year OS rate of 85% in patients without detectable CTC in the blood (p = 0.002). Detection of DTC in the bone marrow with CK20 RT-PCR was not associated with a worse OS or DFS. Detection of pan-cytokeratin positive DTC in the bone marrow correlated with a significantly reduced 5-year OS rate (p = 0.048), but detection of DTC in the bone marrow with the anti-EpCAM antibody did not significantly influence the 5-year OS rate (p = 0.958). By multivariate analyses only detection of CTC with CK20 RT-PCR in the blood was revealed to be an independent predictor of worse OS (HR1.94; 95% CI 1.0-3.7; p = 0.04) and DFS (HR 1.94; 95% CI 1.1-3.7; p = 0.044).
Detection of CTC with CK20 RT-PCR is a highly specific and independent prognostic marker in colon cancer patients. Detection of DTC in the bone marrow with CK20 RT-PCR or immunohistochemistry with anti-EpCAM antibody is not associated with a negative prognostic influence.
循环肿瘤细胞（CTC）或播散肿瘤细胞（DTC）的检测与结直肠癌患者的不良预后和结局相关，尽管这些细胞的检测尚未成为临床常规检查的一部分。检测肿瘤细胞有几种不同的方法，但目前尚未实施标准化检测方法。
在这项前瞻性单中心研究中，纳入了299例结肠癌患者。使用CK20逆转录聚合酶链反应（RT-PCR）以及抗泛角蛋白和抗上皮细胞黏附分子（EpCAM）抗体的免疫细胞化学染色检测CTC和DTC。主要终点为：手术时CTC和DTC的评估以及与主要肿瘤特征、总生存期（OS）和无病生存期（DFS）的相关性。
血液中可检测到CTC的患者5年总生存率为68%，而血液中未检测到CTC的患者5年总生存率为85%（p = 0.002）。用CK20 RT-PCR检测骨髓中的DTC与较差的总生存期或无病生存期无关。骨髓中泛细胞角蛋白阳性DTC的检测与5年总生存率显著降低相关（p = 0.048），但用抗EpCAM抗体检测骨髓中的DTC对5年总生存率无显著影响（p = 0.958）。多因素分析显示，仅血液中用CK20 RT-PCR检测到CTC是总生存期较差（风险比1.94；95%可信区间1.0 - 3.7；p = 0.04）和无病生存期较差（风险比1.94；95%可信区间1.1 - 3.7；p = 0.044）的独立预测因素。
用CK20 RT-PCR检测CTC是结肠癌患者高度特异且独立的预后标志物。用CK20 RT-PCR检测骨髓中的DTC或用抗EpCAM抗体进行免疫组化检测与不良预后影响无关。
