Prognostic value of chemotherapy-resistant CK19mRNA-positive circulating tumor cells in patients with advanced/metastatic non-small cell lung cancer

Background The detection of circulating tumor cells (CTCs) is of prognostic significance in several tumor types. The present study evaluated the detection and the clinical relevance of CK19 mRNA(+) CTCs in patients with advanced/metastatic non-small cell lung cancer before and after front-line chemotherapy. Patients and methods Peripheral blood was obtained from 642 patients with treatment-naïve unresectable stage IIIB and IV non-small cell lung cancer and from 455 patients after the completion of 1st line chemotherapy. RNA was extracted from peripheral blood mononuclear cells and the detection of CK19 mRNA-positive cells was performed using a quantitative PCR assay. Results Based on the detection limit of the assay, 167 (26.0%) patients had detectable CK19 mRNA(+) CTCs at baseline. The detection of CK19 mRNA(+) CTCs before treatment was not associated with the clinical outcome, but their detection at the end of chemotherapy was associated with significantly decreased PFS and OS [PFS: 2.6 vs 3.8 months ( p = 0.008); OS: 5.7 vs 10.0 months ( p = 0.006) for CK19 mRNA(+) vs CK19 mRNA(−) patients, respectively]. Multivariate analysis revealed that the detection of CK19 mRNA(+) CTCs both before and after chemotherapy emerged as an independent factor associated with reduced PFS (HR: 1.778; p