The prognostic value of circulating tumor cells lacking cytokeratins in metastatic breast cancer patients

Abstract

Aim of study: In this study, we detected epithelial circulating tumor cells (CTCs) that expressed cytokeratins and potential circulating tumor cells (pCTCs) that had lost expression of cytokeratins in metastatic breast cancer (MBC) patients. The aim of the study was to evaluate the prognostic significance of these two kinds of CTCs in MBC patients.

Materials and methods: We detected CTCs and pCTCs from 66 MBC patients using MACS immunomagnetic enrichment technology combined with immunocytochemistry (ICC). A cutoff score of 5 CTCs (or pCTCs) was set as a benchmark for prognosis in patients. Progression free survival (PFS) was calculated and analyzed during the following 24 months.

Results: We evaluated the sensitivity of this method and recovery rates of the CTCs by spiking experiments. The loss number of tumor cells by our method was 0-15. The population with fewer than 5 CTCs showed significantly higher PFS than the group with 5 or more CTCs. The difference in PFS between the patients with 5 or more pCTCs and those with fewer than 5 pCTCs was statistically significant. The presence of these pCTCs more accurately predicted poor prognosis than the CTCs that express cytokeratins.

Conclusions: There is a subset of CTCs that lose epithelial markers such as pCTCs. Due to the heterogeneity of the expression of epithelial antigens in CTCs, different subtypes of CTCs exist. Independently of CTCs, the groups of patients with pCTCs had poorer prognoses.