Prognostic Relevance of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow of Patients with Squamous Cell Carcinoma of the Oral Cavity
Prognostic Relevance of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow of Patients with Squamous Cell Carcinoma of the Oral Cavity
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DOI：
10.1158/1078-0432.ccr-13-1101
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发表时间：
2014-01-15
影响因子：
11.5
通讯作者：
Riethdorf, Sabine
中科院分区：
文献类型：
--
作者：
Groebe, Alexander;Blessmann, Marco;Riethdorf, Sabine
目的：当前口腔鳞状细胞癌（SCC）（OSCC）的分期方法需要改进，以预测个体患者的风险。由于血行肿瘤细胞播散是肿瘤进展的关键事件，因此我们评估了 OSCC 患者骨髓中播散性肿瘤细胞 (DTC) 和外周血中循环肿瘤细胞 (CTC) 的预后意义。 实验设计：110 名 OSCC 患者中，在没有新辅助治疗的情况下手术切除了肿瘤 (R0)。 CellSearch 系统用于计数 CTC。从髂嵴吸出骨髓，通过聚蔗糖密度梯度离心富集单核细胞（MNC）。为了检测 DTC，使用泛角蛋白抗体 A45-B/B3 对 MNC 进行免疫染色。结果与临床病理参数和临床结果相关，例如随访时间（平均 916 天）期间的复发和死亡。结果：80 名患者中的 10 名（12.5%）外周血中检测到 CTC，而 90 名患者中的 18 名（20.0%）骨髓中可检测到 DTC。令人惊讶的是，只有 2 名患者 (1.8%) 同时检测到 CTC 和 DTC。 CTC 与肿瘤大小（P = 0.04）、淋巴结状态和 DTC（P = 0.02）以及远处转移与 CTC（P = 0.004）和 DTC（P = 0.005）之间存在显着相关性。单变量和多变量分析显示，CTC 和 DTC 是无复发生存的显着且独立的预测因子（P < 0.001）。结论：DTC 和 CTC 都是 OSCC 患者的独立预后标志物，与常规分期程序相比，在各个疾病阶段预测复发的敏感性更高。骨髓可能是未来治疗干预的一个有趣的靶器官。 (C) 2013 年 AACR。
Purpose: Current staging methods for squamous cell carcinomas (SCC) of the oral cavity (OSCC) need to be improved to predict the risk of individual patients. Because hematogenous tumor cell dissemination is a key event in tumor progression, we assessed the prognostic significance of disseminated tumor cells (DTC) in bone marrow and circulating tumor cells (CTC) in peripheral blood from patients with OSCC.Experimental Design: From 110 patients with OSCC, tumors were surgically resected (R0) without neoadjuvant therapy. The CellSearch system was used to enumerate CTCs. Bone marrow was aspirated from the iliac crest, and mononuclear cells (MNC) were enriched by Ficoll density gradient centrifugation. To detect DTCs, MNCs were immunostained with the pan-keratin antibody A45-B/B3. Results were correlated with clinicopathologic parameters and clinical outcome such as recurrence and death during follow-up time (mean 916 days).Results: Ten of 80 patients (12.5%) harbored CTCs in peripheral blood, whereas in 18 of 90 patients (20.0%) DTCs in bone marrow could be detected. Surprisingly, in only 2 patients (1.8%) CTCs and DTCs were detected simultaneously. Significant correlations could be found for CTCs and tumor size (P = 0.04), nodal status and DTCs (P = 0.02), and distant metastasis with CTCs (P = 0.004) and DTCs (P = 0.005). Univariate and multivariate analyses revealed that CTCs and DTCs were significant and independent predictors of recurrence-free survival (P < 0.001).Conclusions: Both DTCs and CTCs are independent prognostic markers in patients with OSCC, predicting relapse with higher sensitivity at various disease stages than routine staging procedures. Bone marrow might be an interesting target organ for future therapeutic interventions. (C) 2013 AACR.