Isolated tumor cells in bone marrow predict reduced survival in node-negative non-small cell lung cancer
Isolated tumor cells in bone marrow predict reduced survival in node-negative non-small cell lung cancer
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DOI：
10.1016/s0003-4975(99)01125-x
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发表时间：
1999-12-01
影响因子：
4.6
通讯作者：
Pantel, K
中科院分区：
文献类型：
--
作者：
Passlick, B;Kubuschok, B;Pantel, K
背景最近变得明显的是，通过常规肿瘤分期检测不到的孤立的肿瘤细胞经常存在于具有明显局部化的非小细胞肺癌（NSCLC）的患者的骨髓中。这种最小的造血肿瘤细胞播散的临床相关性正在激烈的辩论中。对于骨髓中的肿瘤细胞检测，我们使用抗上皮中间丝蛋白细胞角蛋白18的单克隆抗体CK 2。研究了139例术后分期为pT（1-4）、pN（0-2）、M-0和R-0的NSCLC患者，中位随访时间为66个月（范围48 - 74个月），骨髓检查阳性对临床结局的影响。初次手术时，83例（59.7%）患者骨髓中的细胞角蛋白-18阳性细胞，术后3至18个月，12例代表性患者中有6例进行了两次分析。在无组织病理学淋巴结转移的患者中（pN（0）; n = 66），在单变量分析中，初次手术时骨髓中出现2个或更多肿瘤细胞是总生存期的强有力的独立预测因素（p = 0.007）。多变量分析显示，与无播散性肿瘤细胞的患者相比，有播散性肿瘤细胞的患者生存期缩短的风险增加2.8倍。6例术后细胞角蛋白状态阳性的患者中有4例在术后II至44个月内出现肿瘤复发，而所有时间间隔骨髓阴性的患者均未出现肿瘤复发。最小残留骨髓受累是淋巴结阴性NSCLC患者总生存期的独立预后因素，这可能有助于识别需要辅助全身治疗的患者。术后骨髓中肿瘤细胞的持续存在或重新出现表明这些不仅是脱落的细胞，而且代表了真正的微转移。(C)1999年，美国胸外科医师协会（Society of Thoracic Surgeons）
Background. It recently became evident that isolated tumor cells undetectable by conventional tumor staging are frequently present in bone marrow of patients with apparently localized non-small cell lung cancer (NSCLC). The clinical relevance of this minimal hematogenous tumor cell dissemination is under vigorous debate.Methods. For tumor cell detection in the bone marrow, we used monoclonal antibody CK2 against the epithelial intermediate filament protein cytokeratin 18. The influence of a positive bone marrow finding on clinical outcome was studied in 139 patients with NSCLC postoperatively staged as pT(1-4), pN(0-2), M-0, and R-0 after a median follow-up of 66 months (range 48 to 74 months).Results. Cytokeratin-18-positive cells in bone marrow were demonstrated in 83 (59.7%) patients at the time of primary surgery and in 6 of 12 representative patients analyzed twice 3 to 18 months after surgery. In patients without histopathological lymph node metastases (pN(0); n = 66), the occurrence of 2 or more tumor cells in bone marrow at primary surgery was a strong and independent predictor for overall survival (p = 0.007) in univariate analysis. The multivariate analysis showed a 2.8 times increased risk for shorter survival in patients with disseminated tumor cells versus patients without such cells. Four of the 6 patients with a positive cytokeratin status after surgery developed a tumor recurrence II to 44 months after the operation, while none of the patients with a negative bone marrow at all time intervals showed a tumor relapse.Conclusions. Minimal residual bone marrow involvement is an independent prognostic factor for overall survival in patients with node-negative NSCLC, which may help to identify patients in need of an adjuvant systemic therapy. The postoperative persistence or reappearance of tumor cells in bone marrow indicates that these are not only shedded cells but rather represent true micrometastasis. (C) 1999 by The Society of Thoracic Surgeons.