EGFR and HER3 expression in circulating tumor cells and tumor tissue from non-small cell lung cancer patients.
Heather ScharpenseelAnnkathrin HanssenSonja LogesMalte MohmeChristian BernreutherSven PeineKatrin LamszusYvonne GoyCordula PetersenManfred WestphalMarkus GlatzelSabine RiethdorfKlaus PantelHarriett WikmanPublished in: Scientific reports (2019)
Although clinically relevant, the detection rates of EpCAM positive CTCs in non-small cell lung cancer (NSCLC) are surprisingly low. To find new clinically informative markers for CTC detection in NSCLC, the expression of EGFR and HER3 was first analyzed in NSCLC tissue (n = 148). A positive EGFR and HER3 staining was observed in 52.3% and 82.7% of the primary tumors, and in 62.7% and 91.2% of brain metastases, respectively. Only 3.0% of the brain metastases samples were negative for both HER3 and EGFR proteins, indicating that the majority of metastases express these ERBB proteins, which were therefore chosen for CTC enrichment using magnetic cell-separation. Enrichment based on either EGFR or HER3 detected CTCs in 37.8% of the patients, while the combination of EGFR/HER3 enrichment with the EpCAM-based CellSearch technique detected a significantly higher number of 66.7% CTC-positive patients (Cohen's kappa = -0.280) which underlines the existence of different CTC subpopulations in NSCLC. The malignant origin of keratin-positive/CD45-negative CTC clusters and single CTCs detected after EGFR/HER3 based enrichment was documented by the detection of NSCLC-associated mutations. In conclusion, EGFR and HER3 expression in metastasized NSCLC patients have considerable value for CTC isolation plus multiple markers can provide a novel liquid biopsy approach.
Keyphrases
- small cell lung cancer
- circulating tumor cells
- brain metastases
- end stage renal disease
- epidermal growth factor receptor
- tyrosine kinase
- newly diagnosed
- ejection fraction
- chronic kidney disease
- poor prognosis
- prognostic factors
- advanced non small cell lung cancer
- peritoneal dialysis
- circulating tumor
- stem cells
- patient reported outcomes
- ultrasound guided
- mesenchymal stem cells
- patient reported
- ionic liquid
- label free
- single cell
- bone marrow
- quantum dots