Detection of circulating tumor cells by p75NTR expression in patients with esophageal cancer

Background: The p75 neurotrophin receptor (p75NTR) is a cancer stem cell (CSC) marker in esophageal squamous cell carcinoma (ESCC). This study aimed to assess the use of p75NTR in detecting circulating tumor cells (CTCs) in ESCC. Methods: Peripheral blood mononuclear cell expression of epithelial cell adhesion molecule (EpCAM) and p75NTR was detected in 23 ESCC patients (13 received chemo or chemoradiotherapy and 10 received curative surgery) and 10 healthy controls by flow cytometry. Results: EpCAM + p75NTR+ cell counts (average ± SD) were significantly higher in patients (n = 23, 16.0 ± 18.3) compared to controls (n = 10, 0.4 ± 0.9, p = 0.013). The sensitivity and specificity to differentiate ESCC patients from controls were 78.3 and 100 % (cut-off value 4.0), respectively. EpCAM + p75NTR+, but not EpCAM + p75NTR- cell counts, correlated with clinically diagnosed distant metastasis (n = 13, p = 0.006) and pathological venous invasion in resected primary tumors (n = 10, p = 0.016). Malignant cytology was microscopically confirmed in isolated EpCAM + p75NTR+ cells with immunocytochemical double staining. Conclusions: p75NTR is suggested to be a useful marker for clinically significant CTCs, which exhibit highly metastatic features in ESCC.