Characterization of circulating tumor cells in newly diagnosed breast cancer

Abstract

Identification of circulating tumor cells (CTCs) by surface marker expression and ploidy analysis [immunostaining-fluorescence in situ hybridization (iFISH)] has been shown to be a highly sensitive method in the identification of certain solid cancers. In the present study, iFISH analysis was performed to identify CTCs in 184 patients with newly diagnosed non-metastatic breast cancer, and the distribution of CTC subtypes was characterized based on cytokeratin (CK) expression and ploidy status. It was revealed that CTCs of non-metastatic, aneuploid breast cancers, independent of CK expression profile, can be detected with high sensitivity (90.76%) by the iFISH system. Higher CTC counts and sensitivity were observed in patients with increased tumor size burden and unfavorable hormone receptor status. Investigation of CTC subtypes based on ploidy analysis indicated that triploid CTCs constituted the majority of CTCs evaluated. While CK-positive CTCs were detected in a small cohort of patients, an overall low rate of CK expression was observed in the 18 patient samples evaluated. Of note, CK expression was rare in CTCs detected in patients with Herceptin 2 (Her2)-positive or triple-negative [estrogen receptor (ER)-, progesterone receptor (PR)- and Her2-negative], indicating that lack of ER and PR may result in promotion of epithelial-mesenchymal transition and enhancement of tumor aggression.

Keywords: breast cancer; circulating tumor cell; cytokeratin; hormone receptor status; ploidy analysis; tumor size.

Figures

Figure 1.

CTC and its subtypes in newly diagnosed patients with breast cancer. (A) Numbers of CTCs with CK-positive or -negative expression, and diploid, triploid, tetraploid and multiploid status are shown. (B) Numbers of CK-positive CTCs according to hormone receptor status are shown. CTC, circulating tumor cell; CK, cytokeratin; Her2, herceptin 2; TNBC, triple negative breast cancer.

Figure 2.

CTC counts and rates in patients with breast cancer. (A) Comparison of CTC detection among patients with different clinical stages. (B) Comparison of CTC detection between patients with LNM and NLNM. (C) CTC counts in patients with different tumor sizes are shown. *P