All circulating EpCAM+CK+CD45- objects predict overall survival in castration-resistant prostate cancer.
BACKGROUND
Presence of five or more circulating tumor cells (CTC) in patients with metastatic carcinomas is associated with poor survival. Although many objects positive for epithelial cell adhesion molecules and cytokeratin (EpCAM+CK+) are not counted as CTC, they may be an important predictor for survival. We evaluated the association between these objects and survival in patients with prostate cancer.


METHODS
Included in this follow-up study were 179 patients with castration-resistant prostate cancer. CellSearch was used to isolate EpCAM+ objects and to stain DNA, cytokeratin and CD45. All EpCAM+CK+ objects were subdivided into seven classes on the basis of predefined morphological appearance in 63 independent samples. Association of each class with survival was studied using Kaplan-Meier and Cox regression analyses.


RESULTS
Each EpCAM+CK+CD45- class showed a strong association with overall survival (P < 0.001). This included small tumor microparticles (S-TMP), which did not require a nucleus and thus are unable to metastasize. A higher number of objects in any class was associated with decreased survival. A good prediction model included large tumor cell fragments (L-TCF), age, hemoglobin and lactate dehydrogenase. Models with S-TMP or CTC instead of L-TCF performed similarly.


CONCLUSIONS
EpCAM+CK+CD45- that do not meet strict definitions for CTC are strong prognostic markers for survival.
Coumans
F A W
FAW
Department of Medical Cell BioPhysics, Faculty of Sciences and Technology, MIRA Research Institute, University of Twente. Electronic address: f.a.w.coumans@utwente.nl.
Doggen
C J M
CJM
Department of Health Technology & Services Research, University of Twente, Enschede, The Netherlands.
Attard
G
G
Department of Drug Development Unit, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
de Bono
J S
JS
Department of Drug Development Unit, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
Terstappen
L W M M
LWMM
Department of Medical Cell BioPhysics, Faculty of Sciences and Technology, MIRA Research Institute, University of Twente.
D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood; D002369:Castration; D015815:Cell Adhesion Molecules / Q000097:blood*; D000071858:Epithelial Cell Adhesion Molecule; D005500:Follow-Up Studies; D006801:Humans; D007633:Keratins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000097:blood* / Q000401:mortality* / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood* / Q000401:mortality* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D007633:Keratins