Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Breast Cancer Res Treat. 2011 Feb;125(3):729-38. doi: 10.1007/s10549-010-0911-2. Epub 2010 May 7.
The factors determining the clinical relevance of disseminated tumor cells (DTC) in breast cancer patients are largely unknown. Here we compared the specificity and clinical performance of two antibodies frequently used for DTC detection. Reactivities of antibodies A45-B/B3 (A45) and AE1/AE3 (AE) for selected cytokeratins (CK) were assessed by 2-DE Western Blot analysis. Using these antibodies bone marrow aspirates from 391 breast cancer patients (M(0), pT1-3, pN0-3) were screened for the presence of DTC. To obtain prognostic information, patients were followed up over a median of 83 months for time to relapse and 99 months for time to death. Among the analyzed CK, AE detected CK5, CK7, CK8, and CK19, whereas A45 recognized CK7 and CK18. In total, 24 of 391 patients (6.1%) were DTC-positive for A45, and 41 (10.5%) for AE. Although concordance between the two antibodies was 84.4%, overlap among positive cases was only 3.2%. DTC-positivity with AE and A45 was more frequent in patients of higher nodal status (P=0.019 and P=0.036, respectively). Nearly all patients with A45-positive DTC had hormone receptor-positive tumors (23/24), while detection of AE-positive DTC was more frequent among hormone receptor negative patients (P=0.006). Survival analyses of all patients revealed shorter distant disease-free survival (P=0.039) for patients with A45-positive DTC, whereas the prognostic relevance of AE-positive DTC was restricted to node-positive patients. The clinical utility of immunocytochemical (ICC) DTC detection depends on the anti-CK antibody used, which may reflect the complex CK composition of DTC.
在乳腺癌患者中，决定播散肿瘤细胞（DTC）临床相关性的因素在很大程度上尚不清楚。在此，我们比较了两种常用于 DTC 检测的抗体的特异性和临床性能。通过二维电泳 Western blot 分析评估了抗体 A45-B/B3（A45）和 AE1/AE3（AE）对选定细胞角蛋白（CK）的反应性。使用这些抗体，对 391 例乳腺癌患者（M（0）、pT1-3、pN0-3）的骨髓抽吸物进行了 DTC 存在的筛查。为了获得预后信息，对患者进行了中位时间为 83 个月的复发时间和 99 个月的死亡时间随访。在所分析的 CK 中，AE 检测到 CK5、CK7、CK8 和 CK19，而 A45 则识别 CK7 和 CK18。总的来说，在 391 例患者中，有 24 例（6.1%）A45 阳性，41 例（10.5%）AE 阳性。尽管两种抗体之间的一致性为 84.4%，但阳性病例之间的重叠仅为 3.2%。AE 和 A45 的 DTC 阳性在淋巴结状态较高的患者中更为常见（P=0.019 和 P=0.036）。所有 A45 阳性 DTC 患者几乎均为激素受体阳性肿瘤（23/24），而 AE 阳性 DTC 的检测在激素受体阴性患者中更为常见（P=0.006）。所有患者的生存分析显示，A45 阳性 DTC 患者的远处无病生存时间较短（P=0.039），而 AE 阳性 DTC 的预后相关性仅限于淋巴结阳性患者。免疫细胞化学（ICC）DTC 检测的临床实用性取决于所用的抗 CK 抗体，这可能反映了 DTC 的复杂 CK 组成。
