TY - JOUR
T1 - Characterization of Urothelial Cancer Circulating Tumor Cells with a Novel Selection-Free Method
AU - Chalfin, Heather J.
AU - Kates, Max
AU - van der Toom, Emma E.
AU - Glavaris, Stephanie
AU - Verdone, James E.
AU - Hahn, Noah M.
AU - Pienta, Kenneth J.
AU - Bivalacqua, Trinity J.
AU - Gorin, Michael A.
PY - 2018
Y1 - 2018
N2 - To investigate circulating tumor cells (CTCs) as biomarkers of urothelial carcinoma (UC). The majority of this work to date has utilized the CellSearch test, which has limited sensitivity due to reliance on positive selection for the cell surface protein EpCAM. We used a novel selection-free method to enumerate and characterize CTCs across a range of UC stages. Blood samples from 38 patients (9 controls, 8 non-muscle invasive bladder cancer [NMIBC], 12 muscle-invasive bladder cancer [MIBC] and 9 metastatic UC) were processed with the AccuCyte-CyteFinder system. Slides were stained for the white blood cell (WBC) markers CD45 and CD66b and the epithelial markers EpCAM and pancytokeratin (CK). CTCs were defined as any CK+/WBC- cell. Separately, the more restrictive CellSearch definition was applied, with the additional requirement of EpCAM positivity. The Kruskal-Wallis ANOVA test compared CTC counts by stage. ≥1 CTC was detected in 2/8(25%) patients with NMIBC, 7/12(58%) with MIBC, and 6/9(67%) with metastatic disease. No control had CTCs. Comparing CTC counts between groups, the only statistically significant comparison was between controls and patients with metastatic UC (p=0.009). With EpCAM positivity as a CTC requirement, no CTCs were detected in any NMIBC patient, and only 2(17%) MIBC patients had CTCs. CTCs tended to be larger in metastatic patients. CTCs were detected at all UC stages and exhibited phenotypic diversity of cell size and EpCAM expression. EpCAM negative CTCs that would be missed with the CellSearch test were detected in NMIBC and MIBC patients
AB - To investigate circulating tumor cells (CTCs) as biomarkers of urothelial carcinoma (UC). The majority of this work to date has utilized the CellSearch test, which has limited sensitivity due to reliance on positive selection for the cell surface protein EpCAM. We used a novel selection-free method to enumerate and characterize CTCs across a range of UC stages. Blood samples from 38 patients (9 controls, 8 non-muscle invasive bladder cancer [NMIBC], 12 muscle-invasive bladder cancer [MIBC] and 9 metastatic UC) were processed with the AccuCyte-CyteFinder system. Slides were stained for the white blood cell (WBC) markers CD45 and CD66b and the epithelial markers EpCAM and pancytokeratin (CK). CTCs were defined as any CK+/WBC- cell. Separately, the more restrictive CellSearch definition was applied, with the additional requirement of EpCAM positivity. The Kruskal-Wallis ANOVA test compared CTC counts by stage. ≥1 CTC was detected in 2/8(25%) patients with NMIBC, 7/12(58%) with MIBC, and 6/9(67%) with metastatic disease. No control had CTCs. Comparing CTC counts between groups, the only statistically significant comparison was between controls and patients with metastatic UC (p=0.009). With EpCAM positivity as a CTC requirement, no CTCs were detected in any NMIBC patient, and only 2(17%) MIBC patients had CTCs. CTCs tended to be larger in metastatic patients. CTCs were detected at all UC stages and exhibited phenotypic diversity of cell size and EpCAM expression. EpCAM negative CTCs that would be missed with the CellSearch test were detected in NMIBC and MIBC patients
U2 - https://doi.org/10.1016/j.urology.2018.01.036
DO - https://doi.org/10.1016/j.urology.2018.01.036
M3 - Article
C2 - 29432873
SN - 0090-4295
VL - 115
SP - 82
EP - 86
JO - Urology
JF - Urology
ER -