Clinical significance of immunocytochemical detection of tumor cells using digital microscopy in peripheral blood and bone marrow of breast cancer patients
Clinical significance of immunocytochemical detection of tumor cells using digital microscopy in peripheral blood and bone marrow of breast cancer patients
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DOI：
10.1158/1078-0432.ccr-0102-03
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发表时间：
2004-02-15
影响因子：
11.5
通讯作者：
Magdelénat, H
中科院分区：
文献类型：
--
作者：
Pierga, JY;Bonneton, C;Magdelénat, H
目的：据报道，骨髓中肿瘤细胞的存在是乳腺癌的重要预后指标，但外周血中循环细胞的临床意义尚不清楚。本研究的目的是评估利用自动辅助免疫组化检测系统鉴定外周血中表达细胞角蛋白（CK）的细胞的可行性，并将其与骨髓样本中肿瘤细胞的检测进行比较。 实验设计：同时获得 114 名处于不同阶段的乳腺癌患者的外周血和骨髓的细胞纺丝 Ficoll 级分。 化疗前的疾病（I 至 IV）。全细胞角蛋白 (CK) 单克隆抗体 A45-B/B3（抗 CK 8、18 和 19）用于上皮细胞检测。通过自动细胞成像系统（ChromaVision 医疗系统）检测免疫染色细胞。结果：在 28 名患者（24.5%）的血液中和 67 名患者（59%）的骨髓中检测到 CK+ 细胞。 26 名 (93%) 血液中 CK 阳性细胞的患者骨髓也呈阳性 (P < 0.001)。在 3/39 (7.5%) 可手术乳腺癌（I/II 期）、36 例局部晚期乳腺癌（III 期）中的 9 例（25%）和 39 例转移性疾病（IV 期；P = 0.017）患者中的 16 例（41%）中检测到阳性细胞。在非转移性患者亚组中（n = 75），无病生存率较差的预后因素包括： 缺乏雌激素受体；骨髓中存在 CK+ 细胞 (P = 0.012)；临床淋巴结受累；肿瘤尺寸较大（T4）；以及肿瘤栓子的存在。外周血中循环CK+细胞的存在与无病生存没有统计学相关性。在多变量分析中，无病生存的独立指标是：缺乏雌激素受体（P = 0.043）和骨髓中存在 CK+ 细胞（P = 0.076）。结论：目前的数据不支持循环上皮细胞作为预后因素的临床相关性，特别是与骨髓中的肿瘤细胞相比。然而，这种检测方法可能有助于监测晚期或转移性乳腺癌的治疗效果。
Purpose: The presence of tumor cells in bone marrow has been reported to represent an important prognostic indicator in breast cancer, but the clinical significance of circulating cells in peripheral blood is less well known. The aim of this study was to evaluate the feasibility of identifying cytokeratin (CK)-expressing cells in peripheral blood with an automat-assisted immunohistochemical detection system and to compare it with detection of tumor cells in bone marrow samples.Experimental Design: Cytospun Ficoll fractions of peripheral blood and bone marrow were obtained simultaneously in 114 breast cancer patients at different stages of the disease (I to IV) before treatment with chemotherapy. The pancytokeratin (CK) monoclonal antibody A45-B/B3 (anti-CKs 8, 18, and 19) was used for epithelial cell detection. Immunostained cells were detected by an automated cellular imaging system (ChromaVision Medical System).Results: CK+ cells were detected in 28 (24.5%) patients in blood and in 67 (59%) patients in bone marrow. Twenty-six (93%) patients with CK-positive cells in blood also had positive bone marrow (P < 0.001). Positive cells were detected in peripheral blood in 3/39 (7.5%) operable breast cancers (stage I/II), 9 of 36 (25%) locally advanced breast cancers (stage III), and 16 of 39 (41%) patients with metastatic disease (stage IV; P = 0.017). In the subgroup of nonmetastatic patients (n = 75), prognostic factors for poor disease-free survival were: absence of estrogen receptor; presence of CK+ cells in bone marrow (P = 0.012); clinical nodal involvement; large tumor size (T4); and presence of tumor emboli. Presence of circulating CK+ cells in the peripheral blood was not statistically correlated with disease-free survival. On multivariate analysis, independent indicators for disease-free survival were: absence of estrogen receptor (P = 0.043) and presence of CK+ cells in bone marrow (P = 0.076).Conclusions: The clinical relevance of circulating epithelial cells as a prognostic factor is not supported by the present data, especially in comparison with tumor cells in the bone marrow. However, this method of detection may be useful to monitor the efficacy of treatment in advanced or metastatic breast cancer.