Abstract
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.
Highlights
Circulating tumour cells (CTCs) serve as valuable biomarkers
We explored the frequency of CTCs using the CellSearch system and the novel Adna-epithelial-to-mesenchymal transition (EMT)-2 test to study the appearance of another CTC subpopulation besides the strictly EpCAM-positive CTCs in non-small cell lung cancer (NSCLC) and investigated the molecular properties of these cells
In order to analyse whether EpCAM might get lost during NSCLC cancer progression, EpCAM protein expression was investigated in primary lung tumours (n = 55) as well as brain metastases (n = 76) by IHC
Summary
Circulating tumour cells (CTCs) serve as valuable biomarkers. EpCAM positive CTCs are less frequently detected in NSCLC patients compared to other epithelial tumours. EpCAM protein expression was analysed in primary and metastatic lung cancer tissue. Even after complete primary tumour resection, about 45% of early stage non-small cell lung cancer (NSCLC) patients develop local or distant recurrence within 8 to 18 months[2]. These distant metastases originate from single migratory tumour cells that, detached from the primary tumour, survive in the circulation and colonize distant target tissue. We assessed the frequency of EpCAM expression in both primary tumours and metastatic tissue of NSCLC patients. We explored the frequency of CTCs using the CellSearch system and the novel Adna-EMT-2 test to study the appearance of another CTC subpopulation besides the strictly EpCAM-positive CTCs in NSCLC and investigated the molecular properties of these cells
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