Utility of CK8/18 in identifying circulating tumor cells derived from lesions in patients with non-small cell lung cancer.

Background: Circulating tumor cells (CTCs) are identified by the absence of pan-leukocyte markers and positive staining for cytokeratin (CK). Anti-panCK antibody (AE1/AE3) is a widely used marker for CK. However, epithelial-mesenchymal transition reduces the expression of panCK markers, leading to low detection rates of CTCs, especially in non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy of a novel CTC detection system using CK8/18 as an epithelial cell marker in patients with NSCLC.

Methods: A total of 20 patients with NSCLC (10 EGFR mutant and 10 EGFR wild-type) were included in this study. Blood samples were examined using the novel CTC detection system. Both anti-panCK and anti-CK8/18 antibodies were used to identify CK and detect CTCs. Additionally, CTCs isolated from patients with EGFR mutations underwent single-cell sorting, whole genome amplification, and gene analysis to verify their lung cancer origin.

Results: CTCs were detected in 17 patients (8 EGFR mutant and 9 EGFR wild-type) using CK8/18 and in only 8 patients (5 EGFR mutant and 3 EGFR wild-type) using panCK. The sensitivity of CTC detection based on CK8/18 was significantly higher than that based on panCK (85% vs. 40%, P<0.01). Among the 10 patients with EGFR mutations, EGFR mutations were confirmed in CTCs obtained from six patients in the gene analysis through single-cell sorting, aligning with mutations identified in tissue samples.

Conclusions: This study demonstrated the effectiveness of CK8/18 over panCK in detecting CTCs. Adopting CK8/18 in the novel system improved the detection rate of CTCs, highlighting its potential in clinical applications.