Presence of EpCAM-positive circulating tumor cells as biomarker for systemic disease strongly correlates to survival in patients with hepatocellular carcinoma

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.

Keywords: CellSearch™ system; cancer stem cells; circulating tumor cells; epithelial cell adhesion molecule; hepatocellular carcinoma.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / blood*
  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / mortality*
  • Carcinoma, Hepatocellular / secondary
  • Case-Control Studies
  • Cell Adhesion Molecules / blood*
  • Epithelial Cell Adhesion Molecule
  • Female
  • Follow-Up Studies
  • Humans
  • Liver Neoplasms / blood
  • Liver Neoplasms / mortality*
  • Liver Neoplasms / pathology
  • Male
  • Microscopy, Fluorescence
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / pathology*
  • Prognosis
  • Prospective Studies
  • Survival Rate


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule