Frequency and prognostic significance of isolated tumour cells in bone marrow of patients with non-small-cell lung cancer without overt metastases
Frequency and prognostic significance of isolated tumour cells in bone marrow of patients with non-small-cell lung cancer without overt metastases
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DOI：
10.1016/s0140-6736(96)91203-9
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发表时间：
1996-03-09
期刊：
影响因子：
168.9
通讯作者：
Riethmuller, G
中科院分区：
文献类型：
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作者：
Pantel, K;Izbicki, J;Riethmuller, G
背景转移通常被认为是上皮肿瘤自然史中的晚期事件。方法采用免疫细胞化学方法对139例无远处转移（pT（1-4）pN（1-2）M（0））的非小细胞肺癌患者的骨髓进行检测。用抗细胞角蛋白多肽18的单克隆抗体CK 2检测骨髓抽吸物中的肿瘤细胞。术后患者平均随访39个月（范围14-52）。215例无上皮癌（即，良性上皮肿瘤，非上皮性肿瘤，或炎症性疾病）作为controls.Findings在83 139例（59.7%）患者中检测到细胞角蛋白阳性细胞的频率为1/100 000至1/1 000 000。即使没有淋巴结的组织病理学受累（pN（0）），70例患者中有38例（54.3%）发现肿瘤细胞。在215个对照中的6个中各发现1个阳性细胞。原发性肿瘤切除术期间的手术操作并不影响这些细胞的频率。在考克斯回归分析中，这种细胞的存在是淋巴结阴性患者后期临床复发的一个重要和独立的预测因子（p=0.028）。这些细胞的发现可能有助于决定个体患者是否需要辅助全身治疗。
Background Metastasis is generally looked on as a late event in the natural history of epithelial tumours. However, the poor prognosis of patients with apparently localised lung cancer indicates that micrometastases occur often before diagnosis of the primary tumour.Methods At primary surgery, disseminated tumour cells were detected immunocytochemically in bone marrow of 139 patients with non-small-cell lung carcinomas without evidence of distant metastases (pT(1-4)pN(1-2)M(0)). Tumour cells in bone-marrow aspirates were detected with monoclonal antibody CK2 against cytokeratin polypeptide 18. Patients were followed up for a median of 39 months (range 14-52) after surgery. 215 patients without epithelial cancer (ie, with benign epithelial tumours, nonepithelial neoplasms, or inflammatory diseases) acted as controls.Findings In 83 of 139 (59.7%) patients cytokeratin-positive cells were detected at frequencies of 1 in 100 000 to 1 in 1 000 000. Even without histopathological involvement of lymph nodes (pN(0)), tumour cells were found in 38 of 70 (54.3%) patients. 1 positive cell was found in each of 6 out of 215 controls. Surgical manipulation during primary tumour resection did not affect the frequency of these cells. In Cox's regression analyses, the presence of such cells was a significant and independent predictor for a later clinical relapse in node-negative patients (p=0.028).Interpretation Early dissemination of isolated tumour cells is a frequent and intrinsic characteristic of non-small-cell lung carcinomas. The finding of these cells may help to decide whether adjuvant systemic therapy is required for the individual patient.