Analysis of neuroendocrine marker synaptophysin and stem-cell related marker CD133 on circulating tumor cells (CTC) in patients with metastatic non-small cellular lung cancer (NSCLC).

Abstract

e18010 Background: In NSCLC heterogeneity or switch to neuroendocrine phenotype and the expression of stem-cell related markers have been associated with higher tumor aggressiveness. We evaluated the presence of CTC bearing stem cell-related marker CD133+ and the neuroendocrine marker synaptophysin (SYP) in patients with metastatic non small cellular lung cancer (NSCLC). Methods: Forty-four blood samples (20 mL) were collected after informed consent from 16 consecutive patients (pts) with metastatic NSCLC before and during chemotherapy at our Institution. Blood was enriched for tumor cells by CD45 depletion using a magnetic bead separation technique and potential CTC were identified by flow cytometry. CTC were defined as EpCAM+ CK7/8 + CD45-CD53-. Multiparameter cytometry assessed surface expression of the combinations of CD133 and SYP. Results: CTC phenotype: Twenty-five of all 44 samples (57%) were found positive for presence of at least 1 CTC. The median number of CTC was 4 (range: 1-9) / 10mL blood. Twelve samples (27%) showed to be positive for the cancer putative stem cell marker CD133. The median number of CD133+ CTC was 2 (range: 1-7) / 10mL. Seventeen samples (38%) were positive for SYP with a median number of 2 SYN+ CTC (range: 1-6 ) /10ml. Eleven samples (25%) resulted double positive for CD133 and SYP. Tumor heterogeneity: Twelve of the 16 patients (75%) had at least one sample positive for CTC. In 3 pts (25%) CTC expressed only SYP, in 5 pts (42%) both the markers and in 4 pts (33%) neither CD133 nor SYP were expressed. Conclusions: A higher rate of CD133-SYP-double positive CTC compared to the single positive CTC was observed. This suggests that the switch to the neuroendocrine phenotype might occur concomitantly with a stem-cell like more resistant and aggressive phenotype. It needs to be clarified, whether the presence of stem-cell like and neuroendocrine CTC may be a predictive factor for treatment response and outcome in patients with metastatic NSCLC.