Division of Surgery and Cancer Medicine, Department of Oncology, Oslo University Hospital, Radiumhospitalet, Postboks 4953 Nydalen, 0424, Oslo, Norway.
Breast Cancer Res Treat. 2013 Apr;138(2):485-97. doi: 10.1007/s10549-013-2439-8. Epub 2013 Mar 3.
Detection of disseminated tumour cells (DTCs) in bone marrow by immunocytochemistry (ICC) includes morphological evaluation of cytokeratin immunopositive cells. The aim of this study was to disclose the prognostic significance of different morphological categories of ICC-positive cells according to treatment status and tumour subtype. Bone marrow samples (at surgery) were analysed for the presence of cytokeratin-positive DTCs by a standard immunocytochemical method. The immunopositive cells were classified into the following categories, prior to any analysis of the association between DTCs and clinical outcome: tumour cells (TC), uninterpretable cells (UIC), hematopoietic cells (HC), and questionable HC (QHC). The analysis included 747 early breast cancer patients. Median follow-up was 84 months for relapse, and 99 months for death. The categorisation of the ICC positive cells revealed TC in 13.3 % of the patients, whereas 13.1, 17.8, and 21.4 % of the cases were positive for UIC, QHC, and HC, respectively. Analysing all patients, only TC and UIC predicted systemic relapse. Separate analysis of all patients not receiving adjuvant systemic treatment (No-Adj; n = 389) showed that only QHC were associated with reduced survival (DDFS: p = 0.008; BCSS: p = 0.004, log rank) and the presence of QHC also remained significant in multivariate analysis. Primary tumour subgroup analysis (of all patients) by hormone receptors (HR) and HER2, demonstrated that only TC/UIC had prognostic impact in the HR+/HER2- patients, whereas presence of QHC was associated with unfavourable outcome only in triple negative patients (DDFS: p = 0.004; BCSS: p = 0.024). Patients with ≥3HC had improved outcome compared to those with fewer/no HC (DDFS: p = 0.005; BCSS: p = 0.009). Hence, morphological DTC subgroups may differ in clinical significance according to primary tumour subtype and treatment status. This emphasises the importance of DTC characterisation, and separate analyses of DTC categories according to tumour subtype. Hematopoietic ("false positive") cells might predict an immune-related favorable clinical outcome.
通过免疫细胞化学（ICC）检测骨髓中的播散性肿瘤细胞（DTC）包括对细胞角蛋白免疫阳性细胞的形态学评估。本研究的目的是根据治疗状况和肿瘤亚型，揭示 ICC 阳性细胞不同形态类别的预后意义。通过标准免疫细胞化学方法分析手术时的骨髓样本，以检测细胞角蛋白阳性 DTC 的存在。在分析 DTC 与临床结局之间的关联之前，将免疫阳性细胞分为以下几类：肿瘤细胞（TC）、不可解释细胞（UIC）、造血细胞（HC）和可疑 HC（QHC）。该分析包括 747 例早期乳腺癌患者。无病复发的中位随访时间为 84 个月，死亡的中位随访时间为 99 个月。ICC 阳性细胞的分类显示 13.3%的患者 TC，13.1%、17.8%和 21.4%的患者 UIC、QHC 和 HC 阳性。分析所有患者，只有 TC 和 UIC 预测系统性复发。对未接受辅助全身治疗的所有患者（No-Adj；n=389）进行单独分析显示，只有 QHC 与降低生存率相关（DFS：p=0.008；BCSS：p=0.004，log rank），在多变量分析中 QHC 仍然具有显著意义。根据激素受体（HR）和 HER2 对所有患者的原发肿瘤亚组分析显示，仅 TC/UIC 在 HR+/HER2-患者中有预后影响，而 QHC 的存在仅与三阴性患者的不良预后相关（DFS：p=0.004；BCSS：p=0.024）。与 HC 较少/无 HC 的患者相比，≥3HC 的患者结局改善（DFS：p=0.005；BCSS：p=0.009）。因此，根据原发肿瘤亚型和治疗状况，形态学 DTC 亚组在临床意义上可能存在差异。这强调了 DTC 特征描述的重要性，以及根据肿瘤亚型对 DTC 类别进行单独分析的重要性。造血（“假阳性”）细胞可能预示着与免疫相关的有利临床结局。
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