Circulating tumour cells (CTCs) serve as valuable biomarkers. However, EpCAM
positive CTCs are less frequently detected in NSCLC patients compared to other
epithelial tumours. First, EpCAM protein expression was analysed in primary
and metastatic lung cancer tissue. In both groups 21% of the samples were
EpCAM negative. Second, the CellSearch system identified 15% of patients (n =
48) as CTC positive whereas a multiplex RT-PCR for PIK3CA, AKT2, TWIST, and
ALDH1 following EGFR, HER2 and EpCAM based enrichment detected CTCs in 29% of
the patients. Interestingly, 86% of CTC positive patients were found to
express ALDH1. Only 11% of the patients were CTC-positive by both techniques.
CTC positivity was associated with patient disease state when assessed by the
multiplex RT-PCR assay (p = 0.015). Patients harbouring tumours with an
altered EGFR genotype were more frequently CTC-positive compared to patients
with EGFR wildtype tumours. In subsets of patients, CTCs were found to express
genes involved in resistance to therapy such as HER3 and MET. In conclusion,
using multiple targets for CTC capture and identification increases the
sensitivity of CTC detection in NSCLC patients, which can be explained by the
presence of different CTC subtypes with distinct molecular features