I. Department of Medicine, Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Int J Cancer. 2013 Nov;133(9):2165-71. doi: 10.1002/ijc.28230. Epub 2013 Jun 11.
Current imaging technologies do not sufficiently detect micrometastasis and therefore do not allow adequate stratification of patients with hepatocellular carcinoma (HCC) for curative or systemic therapy. In HCC, presence of stem cell-like, epithelial cell adhesion molecule (EpCAM)-positive cells correlates with tumor aggressiveness and formation of metastasis. Therefore, we investigated the prognostic relevance of EpCAM-positive circulating tumor cells (CTCs) in patients with HCC. Blood from 78 patients (19 patients in the control cohort and 59 patients with HCC) was tested for CTCs with the CellSearch™ system. Correlation analysis to overall survival (OS), the Barcelona Clinic Liver Cancer (BCLC) staging system, macroscopic and microscopic vascular invasion and alpha-fetoprotein (AFP) levels were performed. We detected ≥1 CTC in 18/59 HCC patients and in 1/19 patients with cirrhosis or benign hepatic tumor (p = 0.026). OS was significantly shorter (460 vs. 746 days) in the CTC-positive cohort (p = 0.017). Comparing BCLC stages, significant differences in CTC detection rates were also observed: BCLC stages A 1/9, B 6/31 and C 11/19 (p = 0.006). Ten of 18 patients with macroscopic and 10/16 patients with microscopic vascular invasion exhibited positive findings in CTC testing (p = 0.004 and p = 0.006). Furthermore, CTC results correlated to AFP (cutoff > 400 ng/mL) levels (p = 0.050). Our study demonstrates frequent presence of EpCAM-positive CTC in patients with intermediate or advanced HCC and its prognostic value for OS with possible implications for future treatment stratification.
目前的成像技术不能充分检测到微转移，因此不能对肝细胞癌 (HCC) 患者进行充分的分层，以进行治愈或系统治疗。在 HCC 中，存在具有干细胞样特性的上皮细胞黏附分子 (EpCAM) 阳性细胞与肿瘤侵袭性和转移形成相关。因此，我们研究了 EpCAM 阳性循环肿瘤细胞 (CTC) 在 HCC 患者中的预后相关性。用 CellSearch™系统检测了 78 名患者（19 名对照组患者和 59 名 HCC 患者）的血液中的 CTC。进行了与总生存期 (OS)、巴塞罗那临床肝癌 (BCLC) 分期系统、宏观和微观血管侵犯以及甲胎蛋白 (AFP) 水平的相关性分析。我们在 59 名 HCC 患者中的 18 名和 19 名肝硬化或良性肝肿瘤患者中的 1 名中检测到≥1 CTC(p = 0.026)。在 CTC 阳性组中，OS 明显缩短（460 与 746 天；p = 0.017）。比较 BCLC 分期，也观察到 CTC 检测率的显著差异：BCLC 分期 A 1/9、B 6/31 和 C 11/19(p = 0.006)。18 名宏观血管侵犯患者中有 10 名和 16 名微观血管侵犯患者中有 10 名在 CTC 检测中阳性（p = 0.004 和 p = 0.006）。此外，CTC 结果与 AFP（>400ng/ml 截断值）水平相关（p = 0.050）。我们的研究表明，在中晚期 HCC 患者中经常存在 EpCAM 阳性 CTC，其对 OS 的预后价值可能对未来的治疗分层有影响。
