The presence of high expressing epithelial cell adhesion molecule (EpCAM^high) circulating tumor cells (CTC) enumerated by CellSearch^® in blood of cancer patients is strongly associated with poor prognosis. This raises the question about the presence and relation with clinical outcome of low EpCAM expressing CTC (EpCAM^low CTC). In the EU-FP7 CTC-Trap program, we investigated the presence of EpCAM^high and EpCAM^low CTC using CellSearch, followed by microfiltration of the EpCAM^high CTC depleted blood. Blood samples of 108 castration-resistant prostate cancer patients and 22 metastatic breast cancer patients were processed at six participating sites, using protocols and tools developed in the CTC-Trap program. Of the prostate cancer patients, 53% had ≥5 EpCAM^high CTC and 28% had ≥5 EpCAM^low CTC. For breast cancer patients, 32% had ≥5 EpCAM^high CTC and 36% had ≥5 EpCAM^low CTC. 70% of prostate cancer patients and 64% of breast cancer patients had in total ≥5 EpCAM^high and/or EpCAM^low CTC, increasing the number of patients in whom CTC are detected. Castration-resistant prostate cancer patients with ≥5 EpCAM^high CTC had shorter overall survival versus those with <5 EpCAM^high CTC (p = 0.000). However, presence of EpCAM^low CTC had no relation with overall survival. This emphasizes the importance to demonstrate the relation with clinical outcome when presence of CTC identified with different technologies are reported, as different CTC subpopulations can have different relations with clinical outcome.

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