Banys Malgorzata, Hahn Markus, Gruber Ines, Krawczyk Natalia, Wallwiener Markus, Hartkopf Andreas, Taran Florin-Andrei, Röhm Carmen, Kurth Ralf, Becker Sven, Solomayer Erich-Franz, Wallwiener Diethelm, Staebler Annette, Fehm Tanja
Department of Obstetrics and Gynecology, University of Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany,
Breast Cancer Res Treat. 2014 Apr;144(3):531-8. doi: 10.1007/s10549-014-2898-6. Epub 2014 Mar 4.
Hematogenous tumor cell dissemination is a crucial step in systemic disease progression and predicts reduced clinical outcome in breast cancer patients. Only invasive cancers are assumed to shed tumor cells into the bloodstream and infiltrate lymph nodes. However, recent studies revealed that disseminated tumor cells (DTCs) may be detected in bone marrow (BM) of patients with preinvasive lesions, i.e., ductal carcinoma in situ (DCIS). The purpose of this analysis was to examine the incidence and clinical value of DTC detection in a large series of patients with pure DCIS. 404 patients treated for DCIS at the University Hospital Tuebingen, Germany were included into this analysis. BM was analyzed by immunocytochemistry (pancytokeratin antibody A45-B/B3) using ACIS system (Chromavision) according to the ISHAGE evaluation criteria. Sentinel nodes were analyzed in 316 patients by step sectioning and hematoxylin-eosin staining. DTCs were detected in 63 of 404 patients (16 %). No correlation was observed between BM status and tumor size, grading, histology or Van Nuys prognostic index. In two cases, metastatic spread into lymph nodes was observed; isolated tumor cells were found in one patient. After a median follow-up of 45 months (range 3-131 months), 3 % of BM positive patients died compared to 1 % of BM negative patients (p = 0.254). Relapse of any kind was observed in 7 % of patients with DTCs vs. 5 % of patients without DTCs (p = 0.644). The differences in overall (p = 0.088) and disease-free survival (p = 0.982) calculated by log-rank test were not statistically significant. Tumor cell dissemination may be detected in patients diagnosed with DCIS. Whether these cells disseminate from real preinvasive mammary lesions or represent the earliest step of microinvasion, remains unclear. A longer follow-up may be necessary to accurately assess clinical value of these cells in DCIS patients.
血行性肿瘤细胞播散是系统性疾病进展中的关键步骤，并预示着乳腺癌患者临床预后较差。仅浸润性癌被认为会将肿瘤细胞释放到血液中并浸润淋巴结。然而，最近的研究表明，在原位导管癌（DCIS）等浸润前病变患者的骨髓（BM）中可能检测到播散性肿瘤细胞（DTCs）。本分析的目的是在一大系列单纯DCIS患者中检查DTC检测的发生率和临床价值。纳入了在德国图宾根大学医院接受DCIS治疗的404例患者进行本分析。根据ISHAGE评估标准，使用ACIS系统（Chromavision）通过免疫细胞化学（全细胞角蛋白抗体A45-B/B3）分析骨髓。对316例患者的前哨淋巴结进行连续切片和苏木精-伊红染色分析。404例患者中有63例（16%）检测到DTCs。未观察到骨髓状态与肿瘤大小、分级、组织学或范努伊斯预后指数之间存在相关性。在2例患者中观察到转移至淋巴结；在1例患者中发现孤立的肿瘤细胞。中位随访45个月（范围3 - 131个月）后，骨髓阳性患者中有3%死亡，而骨髓阴性患者中有1%死亡（p = 0.254）。有DTCs的患者中有7%出现任何类型的复发，而无DTCs的患者中有5%出现复发（p = 0.644）。通过对数秩检验计算的总生存率（p = 0.088）和无病生存率（p = 0.982）差异无统计学意义。在诊断为DCIS的患者中可能检测到肿瘤细胞播散。这些细胞是从真正的浸润前乳腺病变中播散而来，还是代表微浸润的最早阶段，仍不清楚。可能需要更长时间的随访来准确评估这些细胞在DCIS患者中的临床价值。
